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Sample records for suppressing capsaicin-induced sensitization

  1. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

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    Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

    2015-01-01

    Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  2. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats

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    Esmaeal Tamaddonfard

    2015-08-01

    Full Text Available Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c. injection of capsaicin (1.5 µg/20 µl into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat and morphine (10 and 40 µg/rat and their co-administration (2.5 and 10 µg/rat of each suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat, was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  3. Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

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    Nicole Schöbel

    Full Text Available Intracellular Cl(- concentrations ([Cl(-](i of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG and olfactory sensory neurons (OSNs, Cl(- is accumulated by the Na(+-K(+-2Cl(- cotransporter 1 (NKCC1, resulting in a [Cl(-](i above electrochemical equilibrium and a depolarizing Cl(- efflux upon Cl(- channel opening. Here, we investigate the [Cl(-](i and function of Cl(- in primary sensory neurons of trigeminal ganglia (TG of wild type (WT and NKCC1(-/- mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-](i of WT TG neurons indicated active NKCC1-dependent Cl(- accumulation. Gamma-aminobutyric acid (GABA(A receptor activation induced a reduction of [Cl(-](i as well as Ca(2+ transients in a corresponding fraction of TG neurons. Ca(2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+ channels (VGCCs. Ca(2+ responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1 were diminished in NKCC1(-/- TG neurons, but elevated under conditions of a lowered [Cl(-](o suggesting a Cl(--dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS, we found expression of different Ca(2+-activated Cl(- channels (CaCCs in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+ imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/- mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+-activated Cl(--dependent signal amplification mechanism in TG neurons that requires intracellular Cl(- accumulation by NKCC1 and the activation of CaCCs.

  4. A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

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    Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

    2014-12-01

    The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

  5. Capsaicin-induced neurogenic inflammation in pig skin: A behavioural study

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    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S

    2014-01-01

    Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments were...... carried out on pigs of 27 ± 5 kg (n = 8) and 57 ± 3 kg (n = 16). Thermal and mechanical noxious stimuli were provided (CO2 laser and Pressure Application Measurement device) to assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia in the smaller pigs (P

  6. Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

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    Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2015-10-01

    During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

  7. Antinociceptive interaction between benfotiamine and resveratrol in capsaicin-induced licking.

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    Montiel-Ruiz, Rosa Mariana; Reyes-García, Gerardo; Flores-Murrieta, Francisco; Déciga-Campos, Myrna

    2009-01-01

    In an attempt to provide more direct evidence concerning the possible antinociceptive effect of resveratrol-benfotiamine combination on neurogenic pain, we investigated whether resveratrol and benfotiamine administered alone or in combination decrease capsaicin induced nociception in mice. Before testing, the animals were placed individually in transparent glass cylinders, 20 cm in diameter, serving as observation chambers. After the adaptation period, 20 microL of capsaicin (1.6 microg/paw) were injected under the skin of the dorsal of the right hind paw. Animals were observed individually for 5 min after capsaicin injection. The amount of time spent licking the injected paw was timed with a chronometer and was considered as indicative of nociception. Animals were pretreated with resveratrol (56.2-177 mg/kg, i.p.), benfotiamine (100-1000 mg/kg, p.o.) and their combinations (11:1, 22:2, 44:4; 88:8 mg/kg benfotiamine:resveratrol). It was observed that resveratrol (ED50 = 104 +/- 8.2 mg/kg) was able to produce more important decrement of capsaicin-induced licking than benfotiamine (ED50 = 529.4 +/- 85.2 mg/kg). In addition, a synergistic interaction was observed between benfotiamine and resveratrol, suggesting that this combination could be useful in neurogenic nociception.

  8. Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

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    Gebhardt, Christine; Albrecht, Doris

    2018-01-01

    Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

  9. Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

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    Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars

    2000-01-01

    We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... and brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine...

  10. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

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    Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

    2013-02-25

    Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

  11. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

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    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  12. Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.

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    Kim, Young Min; Hwang, Jin-Taek; Kwak, Dong Wook; Lee, Yun Kyung; Park, Ock Jin

    2007-01-01

    Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.

  13. Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

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    Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

    2017-11-15

    Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Correction to: Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain.

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    Nakamori, Shunsuke; Takahashi, Jun; Hyuga, Sumiko; Tanaka-Kagawa, Toshiko; Jinno, Hideto; Hyuga, Masashi; Hakamatsuka, Takashi; Odaguchi, Hiroshi; Goda, Yukihiro; Hanawa, Toshihiko; Kobayashi, Yoshinori

    2018-03-01

    The article Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain, written by Shunsuke Nakamori, Jun Takahashi, Sumiko Hyuga, Toshiko Tanaka-Kagawa, Hideto Jinno, Masashi Hyuga, Takashi Hakamatsuka, Hiroshi Odaguchi, Yukihiro Goda, Toshihiko Hanawa and Yoshinori Kobayashi, was originally published Online First without open access. After publication in volume 71, issue 1, page 105-113 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

  15. Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects.

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    Vu, Thuy; Ma, Peiming; Chen, Jiyun Sunny; de Hoon, Jan; Van Hecken, Anne; Yan, Lucy; Wu, Liviawati Sutjandra; Hamilton, Lisa; Vargas, Gabriel

    2017-09-01

    Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.

  16. Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli

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    Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

    2006-01-01

    This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-second stimulation repeated every 30 seconds for 30 minutes. Foot ...

  17. Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

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    S. Stevens Negus

    2012-01-01

    Full Text Available Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+-4-[(αR-α-((2S,5R-4-allyl-2,5-dimethyl-1-piperazinyl-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine. Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg. SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception.

  18. Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner.

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    Oh, Seon Hee; Kim, Young Soon; Lim, Sung Chul; Hou, Yi Feng; Chang, In Youb; You, Ho Jin

    2008-11-01

    Although capsaicin, a pungent component of red pepper, is known to induce apoptosis in several types of cancer cells, the mechanisms underlying capsaicin-induced cytotoxicity are unclear. Here, we showed that dihydrocapsaicin (DHC), an analog of capsaicin, is a potential inducer of autophagy. DHC was more cytotoxic than capsaicin in HCT116, MCF-7 and WI38 cell lines. Capsaicin and DHC did not affect the sub-G(1) apoptotic peak, but induced G(0)/G(1) arrest in HCT116 and MCF-7 cells. DHC caused the artificial autophagosome marker GFP-LC3 to redistribute and upregulated expression of autophagy-related proteins. Blocking of autophagy by 3-methyladenine (3MA) as well as siRNA Atg5 induced a high level of caspase-3 activation. Although pretreatment with zVAD completely inhibited caspase-3 activation by 3MA, it did not prevent cell death. DHC-induced autophagy was enhanced by zVAD pretreatment, as shown by increased accumulation of LC3-II protein. DHC attenuated basal ROS levels through catalase induction; this effect was enhanced by antioxidants, which increased both LC3-II expression and caspase-3 activation. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) abrogated DHC-induced expression of LC3-II, overexpression of the catalase gene increased expression of LC3-II protein, and knockdown decreased it. Additionally, DHC-induced autophagy was independent of p53 status. Collectively, DHC activates autophagy in a p53-independent manner and that may contribute to cytotoxicity of DHC.

  19. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

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    Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

    2014-12-01

    Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection. © 2014 Eur J Oral Sci.

  20. Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.

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    Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

    2007-05-01

    This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).

  1. Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.

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    Bertrand, Helene; Kyriazis, Marylene; Reeves, K Dean; Lyftogt, John; Rabago, David

    2015-11-01

    Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Randomized, placebo-controlled, double-blind clinical trial. Outpatient pain clinic. Twenty-five adults with pain-free lips. Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001). Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect. Copyright © 2015 American

  2. Role of the intraluminal contents and the continuity of intrinsic neurons in intracolonic capsaicin-induced contraction and defecation in dogs.

    Science.gov (United States)

    Kikuchi, Daisuke; Shibata, Chikashi; Imoto, Hirofumi; Someya, Soutoku; Miyachi, Tomohiro; Miura, Koh; Naitoh, Takeshi; Unno, Michiaki

    2014-01-01

    We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation. Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models. In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

  3. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

    Directory of Open Access Journals (Sweden)

    Abu Bakar Ali Asad

    Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

  4. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

  5. Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes

    International Nuclear Information System (INIS)

    Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

    2012-01-01

    Highlights: ► Moderate extracellular acidification regulates intracellular Ca 2+ mobilization. ► Moderate acidification activates NF-κB nuclear translocation in synoviocytes. ► Moderate acidification depresses the ROS production induced by capsaicin. ► Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca 2+ entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca 2+ entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca 2+ release from intracellular stores. The nuclear translocation of NF-κB was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca 2+ mobilization, activating NF-κB nuclear translocation and depressing ROS production.

  6. Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

    Science.gov (United States)

    Sy, M S; Miller, S D; Claman, H N

    1977-07-01

    Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

  7. Rapid and Persistent Suppression of Feeding Behavior Induced by Sensitization Training in "Aplysia"

    Science.gov (United States)

    Acheampong, Ama; Kelly, Kathleen; Shields-Johnson, Maria; Hajovsky, Julie; Wainwright, Marcy; Mozzachiodi, Riccardo

    2012-01-01

    In "Aplysia," noxious stimuli induce sensitization of defensive responses. However, it remains largely unknown whether such stimuli also alter nondefensive behaviors. In this study, we examined the effects of noxious stimuli on feeding. Strong electric shocks, capable of inducing sensitization, also led to the suppression of feeding. The use of…

  8. Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

    Science.gov (United States)

    Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

    2016-07-01

    Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences.

    Science.gov (United States)

    Finkenstaedt, Tim; Del Grande, Filippo; Bolog, Nicolae; Ulrich, Nils; Tok, Sina; Kolokythas, Orpheus; Steurer, Johann; Andreisek, Gustav; Winklhofer, Sebastian

    2018-02-01

     To assess the performance of fat-suppressed fluid-sensitive MRI sequences compared to T1-weighted (T1w) / T2w sequences for the detection of Modic 1 end-plate changes on lumbar spine MRI.  Sagittal T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive patients (consequently 500 vertebral segments; 52 female, mean age 74 ± 7.4 years; 48 male, mean age 71 ± 6.3 years) were retrospectively evaluated. We recorded the presence (yes/no) and extension (i. e., Likert-scale of height, volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and compared the results to fat-suppressed fluid-sensitive sequences (McNemar/Wilcoxon-signed-rank test).  Fat-suppressed fluid-sensitive sequences revealed significantly more Modic I changes compared to T1w/T2w sequences (156 vs. 93 segments, respectively; p definition of Modic I changes is not fully applicable anymore.. · Fat-suppressed fluid-sensitive MRI sequences revealed more/greater extent of Modic I changes.. · Finkenstaedt T, Del Grande F, Bolog N et al. Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences. Fortschr Röntgenstr 2018; 190: 152 - 160. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs.

    NARCIS (Netherlands)

    K. Kapoor (Kapil); U. Arulmani (Udayasankar); J.P. Heiligers (Jan); I.M. Garrelds (Ingrid); E.W. Willems (Edwin); H. Doods (Henri); C.M. Villalón (Carlos); P.R. Saxena (Pramod Ranjan)

    2003-01-01

    textabstract1. Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive trigeminal sensory nerves, seems to be involved in the pathogenesis of migraine. Hence, CGRP receptor antagonists may serve as a novel treatment for migraine. This study

  11. Identifying the Integrated Neural Networks Involved in Capsaicin-Induced Pain Using fMRI in Awake TRPV1 Knockout and Wild-Type Rats

    Directory of Open Access Journals (Sweden)

    Jason Richard Yee

    2015-02-01

    Full Text Available In the present study, we used functional MRI in awake rats to investigate the pain response that accompanies intradermal injection of capsaicin into the hindpaw. To this end, we used BOLD imaging together with a 3D segmented, annotated rat atlas and computational analysis to identify the integrated neural circuits involved in capsaicin-induced pain. The specificity of the pain response to capsaicin was tested in a transgenic model that contains a biallelic deletion of the gene encoding for the transient receptor potential cation channel subfamily V member 1 (TRPV1. Capsaicin is an exogenous ligand for the TRPV1 receptor, and in wild-type rats, activated the putative pain neural circuit. In addition, capsaicin-treated wild-type rats exhibited activation in brain regions comprising the Papez circuit and habenular system, systems that play important roles in the integration of emotional information, and learning and memory of aversive information, respectively. As expected, capsaicin administration to TRPV1-KO rats failed to elicit the robust BOLD activation pattern observed in wild-type controls. However, the intradermal injection of formalin elicited a significant activation of the putative pain pathway as represented by such areas as the anterior cingulate, somatosensory cortex, parabrachial nucleus, and periaqueductal gray. Notably, comparison of neural responses to capsaicin in wild-type versus knock-out rats uncovered evidence that capsaicin may function in an antinociceptive capacity independent of TRPV1 signaling. Our data suggest that neuroimaging of pain in awake, conscious animals has the potential to inform the neurobiological basis of full and integrated perceptions of pain.

  12. Modic type 1 changes. Detection performance of fat-suppressed fluid-sensitive MRI sequences

    Energy Technology Data Exchange (ETDEWEB)

    Finkenstaedt, Tim; Andreisek, Gustav [University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Del Grande, Filippo [Ospedale Regionale di Lugano (Switzerland). Inst. of Diagnostic and Interventional Radiology; Bolog, Nicolae [Phoenix Diagnostic Clinic, Bucharest (Romania); Ulrich, Nils; Tok, Sina [Schulthess Clinic, Zurich (Switzerland). Dept. of Neurosurgery; Kolokythas, Orpheus [Kantonsspital Winterthur (Switzerland). Inst. for Radiology and Nuclear Medicine; Steurer, Johann [University Hospital Zurich (Switzerland). Horten Center for Patient Oriented Research and Knowledge Transfer; Winklhofer, Sebastian [University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; University Hospital Zurich (Switzerland). Dept. of Neuroradiology; Collaboration: LSOS Study Group

    2018-02-15

    To assess the performance of fat-suppressed fluid-sensitive MRI sequences compared to T1-weighted (T1w) / T2w sequences for the detection of Modic 1 end-plate changes on lumbar spine MRI. Sagittal T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive patients (consequently 500 vertebral segments; 52 female, mean age 74 ± 7.4 years; 48 male, mean age 71 ± 6.3 years) were retrospectively evaluated. We recorded the presence (yes/no) and extension (i.e., Likert-scale of height, volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and compared the results to fat-suppressed fluid-sensitive sequences (McNemar/Wilcoxon-signed-rank test). Fat-suppressed fluid-sensitive sequences revealed significantly more Modic I changes compared to T1w/T2w sequences (156 vs. 93 segments, respectively; p < 0.001). The extension of Modic I changes in fat-suppressed fluid-sensitive sequences was significantly larger compared to T1w/T2w sequences (height: 2.53 ± 0.82 vs. 2.27 ± 0.79, volume: 2.35 ± 0.76 vs. 2.1 ± 0.65, end-plate: 2.46 ± 0.76 vs. 2.19 ± 0.81), (p < 0.05). Modic I changes that were only visible in fat-suppressed fluid-sensitive sequences but not in T1w/T2w sequences were significantly smaller compared to Modic I changes that were also visible in T1w/T2w sequences (p < 0.05). In conclusion, fat-suppressed fluid-sensitive MRI sequences revealed significantly more Modic I end-plate changes and demonstrated a greater extent compared to standard T1w/T2w imaging.

  13. Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.

    Science.gov (United States)

    Jantsch, H H F; Gawlitza, M; Geber, C; Baumgärtner, U; Krämer, H H; Magerl, W; Treede, R D; Birklein, F

    2009-05-01

    Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (pmemory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.

  14. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors.

    Science.gov (United States)

    Marichal-Cancino, Bruno A; González-Hernández, Abimael; Manrique-Maldonado, Guadalupe; Ruiz-Salinas, Inna I; Altamirano-Espinoza, Alain H; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2012-10-05

    It has been suggested that during a migraine attack trigeminal nerves release calcitonin gene-related peptide (CGRP), producing central nociception and vasodilatation of cranial arteries, including the extracranial branches of the external carotid artery. Since trigeminal inhibition may prevent this vasodilatation, the present study has investigated the effects of intrathecal dihydroergotamine on the external carotid vasodilatation to capsaicin, α-CGRP and acetylcholine. Anaesthetized vagosympathectomized dogs were prepared to measure blood pressure, heart rate and external carotid conductance. A catheter was inserted into the right common carotid artery for the continuous infusion of phenylephrine (to restore the carotid vascular tone), whereas the corresponding thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C(1)-C(3)) for the administration of dihydroergotamine, the α(2)-adrenoceptor antagonist rauwolscine or the serotonin 5-HT(1B/1D) receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide hydrochloride monohydrate). Intrathecal dihydroergotamine (10, 31 and 100μg) inhibited the vasodilatation to capsaicin, but not that to α-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10μg GR127935 or 100μg rauwolscine, but abolished by 31μg GR127935 or 310μg rauwolscine at 10μg dihydroergotamine; and (ii) abolished by the combination 10μg GR127935+100μg rauwolscine at 100μg dihydroergotamine. Thus, intrathecal (C(1)-C(3)) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT(1B/1D) (probably 5-HT(1B)) receptors and α(2) (probably α(2A/2C))-adrenoceptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Development of a parallel plate proportional counter TRD with suppressed sensitivity to ionization

    International Nuclear Information System (INIS)

    Solomey, N.; Krolak, P.; Graham, G.

    1995-01-01

    The development of a Parallel Plate Proportional Counter which has a highly suppressed sensitivity to ionization but retains a good X-ray signal to noise ratio is presented. Details of the laboratory development and actual beam tests showing the e/π rejection are described. Because of its insensitivity to ionization this type of detector can be useful in an environment where the number of minimum ionizing particles are high, but uninteresting; however, the detector is very sensitive to the highly localized electron cloud from converted X-rays making it ideal as a transition radiation X-ray detector. Thus, this detector only gives a signal for charged particles above TR threshold; all other particles below this threshold produce no TR X-rays giving only a pedestal-like signal. The system's potential performance for π/p separation in the intended neutral Hyperon experiment is evaluated

  16. Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.

    Science.gov (United States)

    Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo

    2017-08-15

    Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

  17. Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

    Science.gov (United States)

    Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

    2000-01-01

    Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

  18. Self-powered photogalvanic phosphorene photodetectors with high polarization sensitivity and suppressed dark current.

    Science.gov (United States)

    Li, Shuaishuai; Wang, Tao; Chen, Xiaoshuang; Lu, Wei; Xie, Yiqun; Hu, Yibin

    2018-04-26

    High polarization sensitivity, suppressed dark current and low energy consumption are all desirable device properties for photodetectors. In this work, we propose phosphorene-based photodetectors that are driven using photogalvanic effects (PGEs). The inversion symmetry of pristine phosphorene is broken using either application of an out-of-plane gate voltage or a heterostructure that is composed of the original phosphorene and blue phosphorene. The potential asymmetry enables PGEs under illumination by polarized light. Quantum transport calculations show that robust photocurrents are indeed generated by PGEs under a zero external bias voltage because of the broken inversion symmetry. These results indicate that the proposed photodetector is self-powered. In addition, the zero bias voltage eliminates the dark currents that are caused by application of an external bias voltage to traditional photodetectors. High polarization sensitivity to both linearly and circularly polarized light can also be realized, with extinction ratios ranging up to 102. The photoresponse of the proposed phosphorene/blue phosphorene heterostructure can be greatly enhanced by gating and is several orders of magnitude higher than that in gated phosphorene.

  19. Mms Sensitivity of All Amino Acid-Requiring Mutants in Aspergillus and Its Suppression by Mutations in a Single Gene

    OpenAIRE

    Käfer, Etta

    1987-01-01

    All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regula...

  20. High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation[S

    Science.gov (United States)

    McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne T.; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry-Anne; Heather, Alison K.

    2014-01-01

    Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. PMID:24347528

  1. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx

    International Nuclear Information System (INIS)

    Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck; Choi, Yung-Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree; Kim, Gi-Young

    2012-01-01

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.

  2. Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

    International Nuclear Information System (INIS)

    Peng, Hui; Wang, Huihui; Xue, Peng; Hou, Yongyong; Dong, Jian; Zhou, Tong; Qu, Weidong; Peng, Shuangqing; Li, Jin; Carmichael, Paul L.; Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2016-01-01

    Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As 2 O 3 ), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As 2 O 3 -challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As 2 O 3 -induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As 2 O 3 -induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As 2 O 3 in AML cells. • Sensitization of THP-1 cells to As 2 O 3 toxicity by ethionamide is NRF2-dependent.

  3. MMS sensitivity of all amino acid-requiring mutants in aspergillus and its suppression by mutations in a single gene.

    Science.gov (United States)

    Käfer, E

    1987-04-01

    All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regulation of amino acid biosynthesis than MMS uptake, since a variety of pathway interactions were clearly modified by smsA suppressors in the absence of MMS.

  4. An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

    Directory of Open Access Journals (Sweden)

    Tokiho Akiyama

    Full Text Available Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05. The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05, and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

  5. Knock-down of NDRG2 sensitizes cervical cancer Hela cells to cisplatin through suppressing Bcl-2 expression

    International Nuclear Information System (INIS)

    Liu, Junye; Guo, Guozhen; Yang, Le; Zhang, Jian; Zhang, Jing; Chen, Yongbin; Li, Kangchu; Li, Yurong; Li, Yan; Yao, Libo

    2012-01-01

    NDRG2, a member of N-Myc downstream regulated gene family, plays some roles in cellular stress, cell differentiation and tumor suppression. We have found that NDRG2 expression in cervical cancer Hela cells increases significantly upon stimulation with cisplatin, the most popular chemotherapeutic agent currently used for the treatment of advanced cervical cancer. This interesting phenomenon drove us to evaluate the role of NDRG2 in chemosensitivity of Hela cells. In the present study, RNA interference was employed to down-regulate NDRG2 expression in Hela cells. RT-PCR and Western blot were used to detect expression of NDRG2, Bcl-2 and Bax in cancer cells. Real-time PCR was applied to detect miR-15b and miR-16 expression levels. Drug sensitivity was determined with MTT assay. Cell cloning efficiency was evaluated by Colony-forming assay. Apoptotic cells were detected with annexin V staining and flow cytometry. In vitro drug sensitivity assay revealed that suppression of NDRG2 could sensitize Hela cells to cisplatin. Down-regulation of NDRG2 didn’t influence the colony-forming ability but promoted cisplatin-induced apoptosis of Hela cells. Inhibition of NDRG2 in Hela cells was accompanied by decreased Bcl-2 protein level. However, Bcl-2 mRNA level was not changed in Hela cells with down-regulation of NDRG2. Further study indicated that miR-15b and miR-16, two microRNAs targetting Bcl-2, were significantly up-regulated in NDRG2-suppressed Hela cells. These data suggested that down-regulation of NDRG2 could enhance sensitivity of Hela cells to cisplatin through inhibiting Bcl-2 protein expression, which might be mediated by up-regulating miR-15b and miR-16

  6. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-07-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the (/sup 3/H)thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced (/sup 3/H)thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% (SD)) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

  7. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    International Nuclear Information System (INIS)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-01-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the [ 3 H]thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced [ 3 H]thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% [SD]) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition

  8. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.

    Science.gov (United States)

    Almeida, Jorge R; Sauce, Delphine; Price, David A; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C; Autran, Brigitte; Sáez-Cirión, Asier; Appay, Victor

    2009-06-18

    CD8(+) T cells are major players in the immune response against HIV. However, recent failures in the development of T cell-based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell-mediated efficacy. CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8(+) T cells from infected donors. We report that attributes of CD8(+) T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy.

  9. Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hui [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Wang, Huihui [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Xue, Peng [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Hou, Yongyong [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Dong, Jian [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan (China); Zhou, Tong [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Peng, Shuangqing [Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Li, Jin; Carmichael, Paul L. [Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Pi, Jingbo, E-mail: jpi@mail.cmu.edu.cn [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States)

    2016-02-01

    Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As{sub 2}O{sub 3}), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As{sub 2}O{sub 3}-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As{sub 2}O{sub 3}-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As{sub 2}O{sub 3}-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As{sub 2}O{sub 3} in AML cells. • Sensitization of THP-1 cells to As{sub 2}O{sub 3} toxicity by ethionamide is NRF2-dependent.

  10. Tris-hydroxymethyl-aminomethane enhances capsaicin-induced intracellular Ca2+ influx through transient receptor potential V1 (TRPV1 channels

    Directory of Open Access Journals (Sweden)

    Satoshi Murakami

    2016-02-01

    Full Text Available Non-selective transient receptor potential vanilloid (TRPV cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1 and the Ca2+-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM and pH 6.5 buffer elicited steep increases in the intracellular Ca2+ concentration ([Ca2+]i, while treatment with THAM (pH 8.5 alone had no effect. However, treatment with THAM (pH 8.5 following capsaicin application elicited a profound, long-lasting increase in [Ca2+]i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca2+]i increases, which could be a mechanism underlying pain induced by basic pH.

  11. Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.

    Science.gov (United States)

    Riemer, A B; Gruber, S; Pali-Schöll, I; Kinaciyan, T; Untersmayr, E; Jensen-Jarolim, E

    2010-03-01

    Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins. Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm. We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays. Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo. Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

  12. Lack of contralateral suppression in transient-evoked otoacoustic emissions in multiple chemical sensitivity: a clinical correlation study

    Directory of Open Access Journals (Sweden)

    Alessandro Micarelli

    2016-01-01

    Full Text Available Multiple chemical sensitivity (MCS is a chronic disorder characterized by a variety of symptoms associated with the exposure to chemicals at a concentration below the toxic level. Previous studies have demonstrated peculiar responses in brain activity in these patients with respect to sensory stimuli while the association between chemical sensitivity and other environmental intolerances such as noise sensitivity has been questioned by researchers. In this study, a cohort of 18 MCS patients underwent transient-evoked otoacoustic emission (TEOAE testing with and without contralateral suppression to evaluate the functionality of the medial olivocochlear (MOC reflex involved in speech-in-noise sensitivity. Results were compared with an age- and gender-matched control group (n = 20 and correlation analysis with disease onset and quick environmental exposure sensitivity inventory (qEESI symptom severity scale was performed. Subjects affected by MCS showed statistically significant impairment of MOC reflex, and the onset of the disease and several symptom subscales showed to be correlated to such reduction in some of the frequencies tested. These data suggest that alterations of MOC reflex could be part of the complex features of this disease although more studies are needed to further explore auditory perception disorders in environmental intolerances.

  13. Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells.

    Science.gov (United States)

    Sun, Shengrong; Wang, Xiong; Wang, Changhua; Nawaz, Ahmed; Wei, Wen; Li, Juanjuan; Wang, Lijun; Yu, De-Hua

    2011-01-01

    The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Suppression of allergic reactions in ovalbumin-sensitized mice by yam storage proteins dioscorins.

    Science.gov (United States)

    Hsu, Yu-Jhen; Weng, Ching-Feng; Lin, Kuo-Wei; Lin, Kuo-Chih

    2013-11-27

    To study the biomedical functions of dioscorins isolated from various species of Dioscorea , we investigated their antiallergic potential using an OVA-induced allergy mouse model. All the dioscorins suppressed allergic reactions by decreasing the serum IgE and histamine levels. The serum IFN-γ and IgG2a levels increased in all the dioscorin-treated mice. The spleen cells from the dioscorin-treated mice also exhibited an up-regulation of IFN-γ secretion in response to ConA stimulation. Although dioscorins did not affect the IgG1 levels, the IL-5 levels decreased to basal levels in mice treated with dioscorins of D. alata or D. japonica and in most of the lymphoid cells of the dioscorin-treated mice in response to ConA stimulation. The decrease of IgE and histamine levels was concomitant with an increase in IFN-γ and IgG2a levels and with a decrease in IL-5 levels, suggesting that dioscorins suppressed the OVA-induced allergic reactions, possibly through modulating an imbalanced Th1/Th2 immune response.

  15. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  16. Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

    Science.gov (United States)

    Yumoto, Masatoshi; Watanabe, Masaru

    2013-01-01

    Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

  17. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    Science.gov (United States)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  18. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lepob/ob mice

    International Nuclear Information System (INIS)

    Sekiya, Motohiro; Yahagi, Naoya; Tamura, Yoshiaki; Okazaki, Hiroaki; Igarashi, Masaki; Ohta, Keisuke; Takanashi, Mikio; Kumagai, Masayoshi; Takase, Satoru; Nishi, Makiko; Takeuchi, Yoshinori; Izumida, Yoshihiko; Kubota, Midori; Ohashi, Ken; Iizuka, Yoko; Yagyu, Hiroaki; Gotoda, Takanari; Nagai, Ryozo; Shimano, Hitoshi; Yamada, Nobuhiro

    2009-01-01

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep ob/ob /HSL -/- ) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lep ob/ob /HSL -/- developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep ob/ob /HSL +/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep +/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep ob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep ob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

  19. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  20. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    International Nuclear Information System (INIS)

    Gustafsson, Ann-Sofie; Abramenkovs, Andris; Stenerlöw, Bo

    2014-01-01

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  1. Magnesia nanoparticles in liquid electrolyte for dye sensitized solar cells: An effective recombination suppressant?

    International Nuclear Information System (INIS)

    Mohanty, Shyama Prasad; Bhargava, Parag

    2013-01-01

    Highlights: ► MgO loaded electrolyte retards recombination at titania/electrolyte interface. ► Recombination reactions are retarded by adsorption of anions on MgO in electrolyte. ► Zeta potential measurements show anionic adsorption on the surface of MgO. ► MgO loaded electrolyte performs efficiently than TBP containing electrolyte. -- Abstract: Recombination reactions at the photoanode/electrolyte interface reduce the photovoltaic conversion efficiency of dye sensitized solar cells (DSSCs). Unlike modification of titania photoanode by coating with MgO which act as a barrier layer toward recombination, addition of MgO nanopowder to electrolyte prevents recombination through adsorption of anions (triiodide/iodide) from electrolyte. In the present study, the surface charge of MgO has been utilized to adsorb anions from electrolyte. This anionic adsorption onto the MgO nanopowders in electrolyte has been confirmed by zeta potential measurements. MgO retards the recombination reaction as efficiently as 4-tert-butylpyridine (TBP) which is the most widely used additive in the electrolyte. Higher photocurrent and conversion efficiency is achieved by using MgO loaded electrolyte as compared to TBP added electrolyte. Dark current measurements show that recombination reactions are effectively retarded by use of MgO loaded electrolytes. Open circuit voltage decay measurements also confirm higher electron lifetime at the titania/electrolyte interface in MgO loaded electrolyte based cell as compared to additive free electrolyte based cell

  2. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

    Science.gov (United States)

    Scarlatti, G; Tresoldi, E; Björndal, A; Fredriksson, R; Colognesi, C; Deng, H K; Malnati, M S; Plebani, A; Siccardi, A G; Littman, D R; Fenyö, E M; Lusso, P

    1997-11-01

    Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain

  3. Effect of e-Cigarette Use on Cough Reflex Sensitivity.

    Science.gov (United States)

    Dicpinigaitis, Peter V; Lee Chang, Alfredo; Dicpinigaitis, Alis J; Negassa, Abdissa

    2016-01-01

    E-cigarettes (e-cigs) have attained widespread popularity, yet knowledge of their physiologic effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on cough reflex sensitivity. Thirty healthy nonsmokers underwent cough reflex sensitivity measurement using capsaicin cough challenge at baseline, 15 min, and 24 h after e-cig exposure (30 puffs 30 s apart). The end point of cough challenge is the concentration of capsaicin inducing five or more coughs (C5). The number of coughs induced by each e-cig inhalation was counted. A subgroup of subjects (n = 8) subsequently underwent an identical protocol with a non-nicotine-containing e-cig. Cough reflex sensitivity was significantly inhibited (C5 increased) 15 min after e-cig use (?0.29; 95% CI, ?0.43 to ?0.15; P < .0001); 24 h later, C5 returned to baseline (0.24; 95% CI, 0.10-0.38; P = .0002 vs post-15-min value). A subgroup of eight subjects demonstrating the largest degree of cough reflex inhibition had no suppression after exposure to a non-nicotine-containing e-cig (P = .0078 for comparison of ?C5 after nicotine vs non-nicotine device). Furthermore, more coughing was induced by the nicotine-containing vs non-nicotine-containing device (P = .0156). A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of cough reflex sensitivity. Exploratory analysis of a subgroup of subjects suggests that nicotine is responsible for this observation. Our data, consistent with previous studies of nicotine effect, suggest a dual action of nicotine: an immediate, peripheral protussive effect and a delayed central antitussive effect. ClinicalTrials.gov; No.: NCT02203162; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Hsp90 inhibitor 17-AAG sensitizes Bcl-2 inhibitor (-)-gossypol by suppressing ERK-mediated protective autophagy and Mcl-1 accumulation in hepatocellular carcinoma cells.

    Science.gov (United States)

    Wang, Bin; Chen, Linfeng; Ni, Zhenhong; Dai, Xufang; Qin, Liyan; Wu, Yaran; Li, Xinzhe; Xu, Liang; Lian, Jiqin; He, Fengtian

    2014-11-01

    Natural BH3-memitic (-)-gossypol shows promising antitumor efficacy in several kinds of cancer. However, our previous studies have demonstrated that protective autophagy decreases the drug sensitivities of Bcl-2 inhibitors in hepatocellular carcinoma (HCC) cells. In the present study, we are the first to report that Hsp90 inhibitor 17-AAG enhanced (-)-gossypol-induced apoptosis via suppressing (-)-gossypol-triggered protective autophagy and Mcl-1 accumulation. The suppression effect of 17-AAG on autophagy was mediated by inhibiting ERK-mediated Bcl-2 phosphorylation while was not related to Beclin1 or LC3 protein instability. Meanwhile, 17-AAG downregulated (-)-gossypol-triggered Mcl-1 accumulation by suppressing Mcl-1(Thr163) phosphorylation and promoting protein degradation. Collectively, our study indicates that Hsp90 plays an important role in tumor maintenance and inhibition of Hsp90 may become a new strategy for sensitizing Bcl-2-targeted chemotherapies in HCC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

    International Nuclear Information System (INIS)

    Harris, Peter S; Foreman, Nicholas K; Vibhakar, Rajeev; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Donson, Andrew M; Knipstein, Jeffrey; Dubuc, Adrian; Taylor, Michael D; Handler, Michael H

    2012-01-01

    Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation

  6. Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-κB and Akt pathways

    International Nuclear Information System (INIS)

    Wang Xia; Chen Wenshu; Lin Yong

    2007-01-01

    Blockage of either nuclear factor-κB (NF-κB) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-κB activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-κB. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-κB activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-κB activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-κB and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-κB and Akt, which may be applied in lung cancer therapy

  7. Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

    2011-10-07

    Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

  8. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.

    Science.gov (United States)

    Choi, Young Eun; Battelli, Chiara; Watson, Jacqueline; Liu, Joyce; Curtis, Jennifer; Morse, Alexander N; Matulonis, Ursula A; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A

    2014-05-15

    The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.

  9. That "poker face" just might lose you the game! The impact of expressive suppression and mimicry on sensitivity to facial expressions of emotion.

    Science.gov (United States)

    Schneider, Kristin G; Hempel, Roelie J; Lynch, Thomas R

    2013-10-01

    Successful interpersonal functioning often requires both the ability to mask inner feelings and the ability to accurately recognize others' expressions--but what if effortful control of emotional expressions impacts the ability to accurately read others? In this study, we examined the influence of self-controlled expressive suppression and mimicry on facial affect sensitivity--the speed with which one can accurately identify gradually intensifying facial expressions of emotion. Muscle activity of the brow (corrugator, related to anger), upper lip (levator, related to disgust), and cheek (zygomaticus, related to happiness) were recorded using facial electromyography while participants randomized to one of three conditions (Suppress, Mimic, and No-Instruction) viewed a series of six distinct emotional expressions (happiness, sadness, fear, anger, surprise, and disgust) as they morphed from neutral to full expression. As hypothesized, individuals instructed to suppress their own facial expressions showed impairment in facial affect sensitivity. Conversely, mimicry of emotion expressions appeared to facilitate facial affect sensitivity. Results suggest that it is difficult for a person to be able to simultaneously mask inner feelings and accurately "read" the facial expressions of others, at least when these expressions are at low intensity. The combined behavioral and physiological data suggest that the strategies an individual selects to control his or her own expression of emotion have important implications for interpersonal functioning.

  10. Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy of patients with differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Mann, K.; Saller, B.; Mehl, U.; Hoermann, R.; Moser, E.

    1988-01-01

    Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T 4 ), 29 patients with triiodothyronine (T 3 ). In 33/43 patients (77%) under T 4 - and in 18/29 patients (62%) under T 3 -treatment basal TSH levels were below 0.1 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment. (orig.) [de

  11. Selective weed suppression by cover crop residues: effects of seed mass and timing of species’sensitivity

    NARCIS (Netherlands)

    Kruidhof, H.M.; Gallandt, E.R.; Haramoto, E.R.; Bastiaans, L.

    2011-01-01

    Laboratory bioassays have shown that large-seeded species better tolerate cover crop residue–mediated stress than small-seeded species. This provides the potential for selective suppression of small-seeded weeds in large-seeded crops. We conducted two field experiments in which seedling emergence of

  12. The link between CD8⁺ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate.

    Science.gov (United States)

    Lissina, Anna; Fastenackels, Solène; Inglesias, Maria C; Ladell, Kristin; McLaren, James E; Briceño, Olivia; Gostick, Emma; Papagno, Laura; Autran, Brigitte; Sauce, Delphine; Price, David A; Saez-Cirion, Asier; Appay, Victor

    2014-02-20

    Although it is established that CD8 T-cell immunity is critical for the control of HIV replication in vivo, the key factors that determine antiviral efficacy are yet to be fully elucidated. Antigen-sensitivity and T-cell receptor (TCR) avidity have been identified as potential determinants of CD8⁺ T-cell efficacy. However, there is no general consensus in this regard because the relationship between these parameters and the control of HIV infection has been established primarily in the context of immunodominant CD8⁺ T-cell responses against the Gag₂₆₃₋₂₇₂ KK10 epitope restricted by human leukocyte antigen (HLA)-B27. To investigate the relationship between antigen-sensitivity, TCR avidity and HIV-suppressive capacity in vitro across epitope specificities and HLA class I restriction elements, we used a variety of techniques to study CD8⁺ T-cell clones specific for Nef₇₃₋₈₂ QK10 and Gag₂₀₋₂₉ RY10, both restricted by HLA-A3, alongside CD8⁺ T-cell clones specific for Gag₂₆₃₋₂₇₂ KK10. For each targeted epitope, the linked parameters of antigen-sensitivity and TCR avidity correlated directly with antiviral efficacy. However, marked differences in HIV-suppressive capacity were observed between epitope specificities, HLA class I restriction elements and viral isolates. Collectively, these data emphasize the central role of the TCR as a determinant of CD8⁺ T-cell efficacy and demonstrate that the complexities of antigen recognition across epitope and HLA class I boundaries can confound simple relationships between TCR engagement and HIV suppression.

  13. Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

    Science.gov (United States)

    Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

    2014-01-01

    Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID

  14. Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

    Science.gov (United States)

    Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

    2005-11-15

    One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

  15. Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors

    International Nuclear Information System (INIS)

    Amin, Oreekha; Beauchamp, Marie-Claude; Nader, Paul Abou; Laskov, Ido; Iqbal, Sanaa; Philip, Charles-André; Yasmeen, Amber; Gotlieb, Walter H.

    2015-01-01

    Impairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors. Using ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay. Cells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor. Targeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors

  16. 3D Isotropic MR Culprit Plaque Visualization of Carotid Plaque Edema and Hemorrhage with Motion Sensitized Blood Suppression

    DEFF Research Database (Denmark)

    Søvsø Szocska Hansen, Esben; Pedersen, Steen Fjord; Bloch, Lars Ø.

    2014-01-01

    hemorrhage and plaque edema may represent advanced stages of atherosclerosis[1, 2]. In this study, we present a novel multi-contrast 3D motion sensitized black-blood CMR imaging sequence, which detects both plaque edema and hemorrhage with positive contrast. Subjects and Methods The 3D imaging sequence...... to lumen was 39.74±6.75. Discussion/Conclusion In conclusion, the proposed 3D isotropic multi-contrast CMR technique detects plaque edema and hemorrhage with positive contrast and excellent black-blood contrast, which may facilitate evaluation of carotid atherosclerosis. Ongoing studies will include CMR...

  17. The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–small-cell Lung Cancer Through Altering STAT3 Expression

    Directory of Open Access Journals (Sweden)

    Cheng-Cao Sun

    2016-01-01

    Full Text Available MicroRNAs have been identified to be involved in center stage of cancer biology. They accommodate cell proliferation and migration by negatively regulate gene expression either by hampering the translation of targeted mRNAs or by promoting their degradation. We characterized and identified the novel miR-9600 and its target in human non–small-cell lung cancer (NSCLC. Our results demonstrated that the miR-9600 were downregulated in NSCLC tissues and cells. It is confirmed that signal transducer and activator of transcription 3 (STAT3, a putative target gene, is directly inhibited by miR-9600. The miR-9600 markedly suppressed the protein expression of STAT3, but with no significant influence in corresponding mRNA levels, and the direct combination of miR-9600 and STAT3 was confirmed by a luciferase reporter assay. miR-9600 inhibited cell growth, hampered expression of cell cycle-related proteins and inhibited cell migration and invasion in human NSCLC cell lines. Further, miR-9600 significantly suppressed tumor growth in nude mice. Similarly, miR-9600 impeded tumorigenesis and metastasis through directly targeting STAT3. Furthermore, we identified that miR-9600 augmented paclitaxel and cisplatin sensitivity by downregulating STAT3 and promoting chemotherapy-induced apoptosis. These data demonstrate that miR-9600 might be a useful and novel therapeutic target for NSCLC.

  18. IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

    Science.gov (United States)

    Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

    2017-10-01

    IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-11-21

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

  20. Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

    2014-01-01

    Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

  1. Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells

    Directory of Open Access Journals (Sweden)

    Sun Xiao-Feng

    2010-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31 is obviously up-regulated in colorectal cancer (CRC, there is no study on the functional roles of miR-31 in CRC. Methods Anti-miR™ miRNA 31 inhibitor (anti-miR-31 is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116p53+/+ and HCT-116p53-/-colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU, cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116p53+/+ and 67.8% in HCT-116p53-/-cell line (p = 0.042 and 0.046. MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116p53+/+ or HCT-116p53-/-. However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044. Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116p53+/+ and HCT-116p53-/-(p = 0.040 and 0.001. The invasive ability of the cells were increased by 8-fold in HCT-116p53+/+ and 2-fold in HCT-116p53-/- (p = 0.045 and 0.009. Suppression of miR-31 had no effect on cell cycle and colony formation (p > 0.05. Conclusions Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.

  2. Repeated thermal stressor causes chronic elevation of baseline corticosterone and suppresses the physiological endocrine sensitivity to acute stressor in the cane toad (Rhinella marina).

    Science.gov (United States)

    Narayan, Edward J; Hero, Jean-Marc

    2014-04-01

    suggest that repeated exposure to extreme thermal stressor could cause chronic stress and consequently suppress the physiological endocrine sensitivity to acute stressors (e.g. pathogenic diseases) in amphibians. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

    Science.gov (United States)

    Huang, Yung-Jen; Lee, Kuan H; Grau, James W

    2017-02-01

    Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2016-04-01

    Full Text Available Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.

  5. Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

    Science.gov (United States)

    Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

    2017-05-30

    We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

  6. msbB deletion confers acute sensitivity to CO2 in Salmonella enterica serovar Typhimurium that can be suppressed by a loss-of-function mutation in zwf

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    Troy Kimberly

    2009-08-01

    Full Text Available Abstract Background Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS, which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in Salmonella, is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations. Results We report here that msbB (or msbB somA Salmonella are highly sensitive to physiological CO2 (5%, resulting in a 3-log reduction in plating efficiency. Under these conditions, msbB Salmonella form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO2 acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of msbB mutants in CO2, indicating that the CO2-induced growth defects are not due to the effect of CO2 on the pH of the media. A transposon insertion in the glucose metabolism gene zwf compensates for the CO2 sensitivity of msbB Salmonella. The msbB zwf mutants grow on agar, or in broth, in the presence of 5% CO2. In addition, msbB zwf strains show improved growth in low pH or high osmolarity media compared to the single msbB mutant. Conclusion These results demonstrate that msbB confers acute sensitivity to CO2, acidic pH, and high osmolarity. Disruption of zwf in msbB mutants restores growth in 5% CO2 and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by msbB and mutations that suppress specific growth defects.

  7. Pre-emptive multimodal analgesia with tramadol and ketamine-lidocaine infusion for suppression of central sensitization in a dog model of ovariohysterectomy.

    Science.gov (United States)

    Kaka, Ubedullah; Rahman, Nor-Alimah; Abubakar, Adamu Abdul; Goh, Yong Meng; Fakurazi, Sharida; Omar, Mohamed Ariff; Chen, Hui Cheng

    2018-01-01

    The effects of pre-emptive infusion of ketamine-lidocaine with tramadol on the suppression of central sensitization were investigated in a dog ovariohysterectomy model. Twelve dogs were randomly assigned to two groups: ketamine-lidocaine-tramadol (KLT) and tramadol (T) groups. Both groups received intravenous tramadol 4 mg/kg body weight as premedication. Immediately after induction, the KLT group received ketamine and lidocaine at 0.5 and 2 mg/kg loading dose, followed by continuous rate infusion of 50 and 100 µg/kg/min, respectively, for 2 hours. Dogs in T group received saline bolus and continuous rate infusion at equi-volume. Intraoperatively, hemodynamic responses to surgical stimulation were recorded, whereas postoperative pain was evaluated using an algometer and short form of the Glasgow composite measure pain scale. Intraoperatively, hemodynamic responses to surgical stimulation were obtunded to a greater degree in KLT compared to T group. Postoperatively, the pain scores increased only for the first hour in KLT group, compared to 12 hours in T group. Mechanical thresholds at the abdomen decreased postoperatively between 12 and 60 hours in KLT group versus the entire 72 hours in T group. Thresholds at tibia and radius in both groups increased in the immediate 1 hour postoperatively, but decreased thereafter. Significant decrement of thresholds from baseline were detected in the tibia at 24, 42, and 60 hours in KLT group compared to 24-72 hours in T group, and in the radius between 36 and 48 hours in T group, but none in KLT group. Addition of pre-emptive ketamine-lidocaine infusion to single intravenous dose of tramadol enhanced attenuation of central sensitization and improved intra- and postoperative analgesia.

  8. Ageing sensitized by iPLA2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

    Science.gov (United States)

    Jiao, Li; Gan-Schreier, Hongying; Zhu, Xingya; Wei, Wang; Tuma-Kellner, Sabine; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

    2017-12-01

    Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA 2 β is a homeostatic PLA 2 by playing a role in phospholipid metabolism and remodeling. Global iPLA 2 β -/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA 2 β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA 2 β -/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA 2 β -/- mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA 2 β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA 2 β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Mechanistic study on the nuclear modifier gene MSS1 mutation suppressing neomycin sensitivity of the mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Zhou, Qiyin; Wang, Wei; He, Xiangyu; Zhu, Xiaoyu; Shen, Yaoyao; Yu, Zhe; Wang, Xuexiang; Qi, Xuchen; Zhang, Xuan; Fan, Mingjie; Dai, Yu; Yang, Shuxu; Yan, Qingfeng

    2014-01-01

    The phenotypic manifestation of mitochondrial DNA (mtDNA) mutations can be modulated by nuclear genes and environmental factors. However, neither the interaction among these factors nor their underlying mechanisms are well understood. The yeast Saccharomyces cerevisiae mtDNA 15S rRNA C1477G mutation (PR) corresponds to the human 12S rRNA A1555G mutation. Here we report that a nuclear modifier gene mss1 mutation suppresses the neomycin-sensitivity phenotype of a yeast C1477G mutant in fermentable YPD medium. Functional assays show that the mitochondrial function of the yeast C1477G mutant was impaired severely in YPD medium with neomycin. Moreover, the mss1 mutation led to a significant increase in the steady-state level of HAP5 (heme activated protein), which greatly up-regulated the expression of glycolytic transcription factors RAP1, GCR1, and GCR2 and thus stimulated glycolysis. Furthermore, the high expression of the key glycolytic enzyme genes HXK2, PFK1 and PYK1 indicated that enhanced glycolysis not only compensated for the ATP reduction from oxidative phosphorylation (OXPHOS) in mitochondria, but also ensured the growth of the mss1(PR) mutant in YPD medium with neomycin. This study advances our understanding of the phenotypic manifestation of mtDNA mutations.

  10. Pre-emptive multimodal analgesia with tramadol and ketamine–lidocaine infusion for suppression of central sensitization in a dog model of ovariohysterectomy

    Directory of Open Access Journals (Sweden)

    Kaka U

    2018-04-01

    Full Text Available Ubedullah Kaka,1,2 Nor-Alimah Rahman,1 Adamu Abdul Abubakar,1,3 Yong Meng Goh,2,4 Sharida Fakurazi,5,6 Mohamed Ariff Omar,4 Hui Cheng Chen1 1Department of Companion Animal Medicine and Surgery, Faculty of Veterinary Medicine, 2Institute of Tropical Agriculture and Food Security, Universiti Putra Malaysia, Serdang, Malaysia; 3Department of Veterinary Surgery and Radiology, Usmanu Danfodiyo University, Sokoto, Nigeria; 4Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, 5Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, 6Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Malaysia Objectives: The effects of pre-emptive infusion of ketamine–lidocaine with tramadol on the suppression of central sensitization were investigated in a dog ovariohysterectomy model.Patients and methods: Twelve dogs were randomly assigned to two groups: ketamine–­lidocaine–tramadol (KLT and tramadol (T groups. Both groups received intravenous tramadol 4 mg/kg body weight as premedication. Immediately after induction, the KLT group received ketamine and lidocaine at 0.5 and 2 mg/kg loading dose, followed by continuous rate infusion of 50 and 100 µg/kg/min, respectively, for 2 hours. Dogs in T group received saline bolus and continuous rate infusion at equi-volume. Intraoperatively, hemodynamic responses to surgical stimulation were recorded, whereas postoperative pain was evaluated using an algometer and short form of the Glasgow composite measure pain scale.Results: Intraoperatively, hemodynamic responses to surgical stimulation were obtunded to a greater degree in KLT compared to T group. Postoperatively, the pain scores increased only for the first hour in KLT group, compared to 12 hours in T group. Mechanical thresholds at the abdomen decreased postoperatively between 12 and 60 hours in KLT group versus the entire 72 hours in T group. Thresholds at tibia and

  11. Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via regulating RSU1.

    Science.gov (United States)

    Phuah, Neoh Hun; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

    2017-01-01

    Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1'S-1'-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera , induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells. The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA. Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression

  12. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

  13. Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1

    Directory of Open Access Journals (Sweden)

    Phuah NH

    2017-03-01

    .  Results: Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression. Overexpression of RSU1 augmented antiproliferative and apoptosis-inducing effects of ACA.  Conclusion: Our findings showed that combination of ACA with miR-629 and RSU1 may provide a potential strategy in treating cervical cancer. Keywords: miR-629, 1'-acetoxychavicol acetate, cervical cancer, Ras suppressor-1, apoptosis, cell proliferation

  14. Fire suppression has led to greater drought-sensitivity in dry conifer forests: tree-ring carbon isotope evidence from Central Oregon

    Science.gov (United States)

    Voelker, S.; Merschel, A. G.; Meinzer, F. C.; Spies, T. A.; Still, C. J.

    2016-12-01

    Mortality events of economically and ecologically important conifers have been widespread across Western North America over recent decades. Many of these events have been linked to "global change-type droughts" characterized by greater temperatures and evaporative demand. In parallel, since the early to mid- 20th century, increasing atmospheric [CO2] has been shown to increase the water use efficiency (WUE) of trees worldwide while conifer forests in western North America have become denser after the advent of modern fire suppression efforts. Therefore, competing hypotheses include that conifer forests have experienced 1) less drought stress due to water savings from increased WUE, 2) more drought stress due to increased demand for water in dense forests with greater leaf area index, or 3) unchanging stress because these two factors have cancelled each other out. To provide a test of these hypotheses we used inter-annual latewood carbon isotope discrimination, Δ13C, across a dry mixed-conifer forest landscape of central Oregon in the rain shadow of the Cascade Mountains. The forests are dominated by old-growth ponderosa pines (Pinus ponderosa) and younger and fire-intolerant grand firs (Abies grandis). Dendrochronological dating of tree establishment and fires scars established sharp declines in fire frequency and associated increases in the densities of grand fir since the early 1900s. Δ13C data for ponderosa pine and grand fir spanned 1830-2013 and 1900-2013, respectively. For our analyses these years were split into periods of high fire frequency (1830-1900), moderate fire frequency (1901-1956) and fire-exclusion (1957-2013). Comparisons of Δ13C to reconstructed Palmer Drought Severity Index values for the same years revealed that leaf gas exchange of both species has been more sensitive to drought during the recent fire-exclusion period compared to previous periods when surface fires kept tree densities much lower. Similar research is needed elsewhere to

  15. Suppressed Belief

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    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  16. Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue.

    Science.gov (United States)

    Guri, Amir J; Hontecillas, Raquel; Ferrer, Gerardo; Casagran, Oriol; Wankhade, Umesh; Noble, Alexis M; Eizirik, Decio L; Ortis, Fernanda; Cnop, Miriam; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

    2008-04-01

    Abscisic acid (ABA) is a natural phytohormone and peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that significantly improves insulin sensitivity in db/db mice. Although it has become clear that obesity is associated with macrophage infiltration into white adipose tissue (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by which insulin-sensitizing compounds modulate their infiltration remain unknown. We used a loss-of-function approach to investigate whether ABA ameliorates insulin resistance through a mechanism dependent on immune cell PPARgamma. We characterized two phenotypically distinct ATM subsets in db/db mice based on their surface expression of F4/80. F4/80(hi) ATMs were more abundant and expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune cells, including macrophages, impaired the ability of ABA to suppress the infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to improve glucose tolerance. We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism.

  17. Suppression of the cough reflex by α2-adrenergic receptor agonists in the rabbit

    Science.gov (United States)

    Cinelli, Elenia; Bongianni, Fulvia; Pantaleo, Tito; Mutolo, Donatella

    2013-01-01

    The α2-adrenergic receptor agonist clonidine has been shown to inhibit citric acid-induced cough responses in guinea pigs when administered by aerosol, but not orally. In contrast, oral or inhaled clonidine had no effect on capsaicin-induced cough and reflex bronchoconstriction in humans. In addition, intravenous administration of clonidine has been shown to depress fentanyl-induced cough in humans. We investigated the effects of the α2-adrenergic receptor agonists, clonidine and tizanidine, on cough responses induced by mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30–50 nL) into the caudal nucleus tractus solitarii (cNTS) and the caudal ventral respiratory group (cVRG) as well as administered intravenously in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections of clonidine into the cNTS or the cVRG reduced cough responses at 0.5 mmol/L and abolished the cough reflex at 5 mmol/L. Bilateral microinjections of 0.5 mmol/L tizanidine into the cNTS completely suppressed cough responses, whereas bilateral microinjections of 5 mmol/L into the cVRG only caused mild reductions in them. Depressant effects on the cough reflex of clonidine and tizanidine were completely reverted by microinjections of 10 mmol/L yohimbine. Intravenous administration of clonidine (80–120 μg/kg) or tizanidine (150–300 μg/kg) strongly reduced or completely suppressed cough responses. These effects were reverted by intravenous administration of yohimbine (300 μg/kg). The results demonstrate that activation of α2-adrenergic receptors in the rabbit exerts potent inhibitory effects on the central mechanism generating the cough motor pattern with a clear action at the level of the cNTS and the cVRG. PMID:24400133

  18. Dye-Sensitized Solar Cells Based on the Principles and Materials of Photosynthesis: Mechanisms of Suppression and Enhancement of Photocurrent and Conversion Efficiency

    Directory of Open Access Journals (Sweden)

    Hiroyoshi Nagae

    2009-10-01

    Full Text Available Attempts have been made to develop dye-sensitized solar cells based on the principles and materials of photosynthesis: We first tested photosynthetic pigments, carotenoids (Cars, chlorophylls (Chls and their derivatives, to find sensitizers showing reasonable performance (photocurrent and conversion efficiency. We then tried to introduce the principles of photosynthesis, including electron transfer and energy transfer from Car to Phe a. Also, we tried co-sensitization using the pheophorbide (Phe a and Chl c2 pair which further enhanced the performance of the component sensitizers as follows: Jsc = 9.0 + 13.8 → 14.0 mA cm–2 and η = 3.4 + 4.6 → 5.4%.

  19. Dye-sensitized solar cells based on the principles and materials of photosynthesis: mechanisms of suppression and enhancement of photocurrent and conversion efficiency.

    Science.gov (United States)

    Koyama, Yasushi; Miki, Takeshi; Wang, Xiao-Feng; Nagae, Hiroyoshi

    2009-10-27

    Attempts have been made to develop dye-sensitized solar cells based on the principles and materials of photosynthesis: We first tested photosynthetic pigments, carotenoids (Cars), chlorophylls (Chls) and their derivatives, to find sensitizers showing reasonable performance (photocurrent and conversion efficiency). We then tried to introduce the principles of photosynthesis, including electron transfer and energy transfer from Car to Phe a. Also, we tried co-sensitization using the pheophorbide (Phe) a and Chl c(2) pair which further enhanced the performance of the component sensitizers as follows: J(sc) = 9.0 + 13.8 --> 14.0 mA cm(-2) and eta = 3.4 + 4.6 --> 5.4%.

  20. Three-in-one approach towards efficient organic dye-sensitized solar cells: aggregation suppression, panchromatic absorption and resonance energy transfer

    Directory of Open Access Journals (Sweden)

    Jayita Patwari

    2017-08-01

    Full Text Available In the present study, protoporphyrin IX (PPIX and squarine (SQ2 have been used in a co-sensitized dye-sensitized solar cell (DSSC to apply their high absorption coefficients in the visible and NIR region of the solar spectrum and to probe the possibility of Förster resonance energy transfer (FRET between the two dyes. FRET from the donor PPIX to acceptor SQ2 was observed from detailed investigation of the excited-state photophysics of the dye mixture, using time-resolved fluorescence decay measurements. The electron transfer time scales from the dyes to TiO2 have also been characterized for each dye. The current–voltage (I–V characteristics and the wavelength-dependent photocurrent measurements of the co-sensitized DSSCs reveal that FRET between the two dyes increase the photocurrent as well as the efficiency of the device. From the absorption spectra of the co-sensitized photoanodes, PPIX was observed to be efficiently acting as a co-adsorbent and to reduce the dye aggregation problem of SQ2. It has further been proven by a comparison of the device performance with a chenodeoxycholic acid (CDCA added to a SQ2-sensitized DSSC. Apart from increasing the absorption window, the FRET-induced enhanced photocurrent and the anti-aggregating behavior of PPIX towards SQ2 are crucial points that improve the performance of the co-sensitized DSSC.

  1. Suppression of the UV-sensitive phenotype of Escherichia coli recF mutants by recA(Srf) and recA(Tif) mutations requires recJ+

    International Nuclear Information System (INIS)

    Thoms, B.; Wackernagel, W.

    1988-01-01

    Mutations in recA, such as recA801(Srf) (suppressor of RecF) or recA441(Tif) (temperature-induced filamentation) partially suppress the deficiency in postreplication repair of UV damage conferred by recF mutations. We observed that spontaneous recA(Srf) mutants accumulated in cultures of recB recC sbcB sulA::Mu dX(Ap lac) lexA51 recF cells because they grew faster than the parental strain. We show that in a uvrA recB+ recC+ genetic background there are two prerequisites for the suppression by recA(Srf) of the UV-sensitive phenotype of recF mutants. (i) The recA(Srf) protein must be provided in increased amounts either by SOS derepression or by a recA operator-constitutive mutation in a lexA(Ind) (no induction of SOS functions) genetic background. (ii) The gene recJ, which has been shown previously to be involved in the recF pathway of recombination and repair, must be functional. The level of expression of recJ in a lexA(Ind) strain suffices for full suppression. Suppression by recA441 at 30 degrees C also depends on recJ+. The hampered induction by UV of the SOS gene uvrA seen in a recF mutant was improved by a recA(Srf) mutation. This improvement did not require recJ+. We suggest that recA(Srf) and recA(Tif) mutant proteins can operate in postreplication repair independent of recF by using the recJ+ function

  2. Interocular suppression

    Science.gov (United States)

    Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

    2017-08-01

    The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

  3. Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells

    Science.gov (United States)

    Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Li, Lin; Chan, Kar-Man; Wong, Eric Chun-Wai; Chan, Judy Yuet-Wah; Fung, Kwok-Pui; Lui, Vivian Wai Yan; Chiu, Philip Wai-Yan; Lau, Clara Bik-San

    2015-01-01

    Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers’ great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP-treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications. PMID

  4. Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells.

    Science.gov (United States)

    Circu, Magdalena; Cardelli, James; Barr, Martin; O'Byrne, Kenneth; Mills, Glenn; El-Osta, Hazem

    2017-01-01

    Lung cancer is the leading cause of cancer-related deaths. Most patients develop resistance to platinum within several months of treatment. We investigated whether triggering lysosomal membrane permeabilization (LMP) or suppressing autophagy can restore cisplatin susceptibility in lung cancer with acquired chemoresistance. Cisplatin IC50 in A549Pt (parental) and A549cisR (cisplatin resistant) cells was 13 μM and 47 μM, respectively. Following cisplatin exposure, A549cisR cells failed to elicit an apoptotic response. This was manifested by diminished Annexin-V staining, caspase 3 and 9, BAX and BAK activation in resistant but not in parental cells. Chloroquine preferentially promoted LMP in A549cisR cells, revealed by leakage of FITC-dextran into the cytosol as detected by immunofluorescence microscopy. This was confirmed by increased cytosolic cathepsin D signal on Immunoblot. Cell viability of cisplatin-treated A549cisR cells was decreased when co-treated with chloroquine, corresponding to a combination index below 0.8, suggesting synergism between the two drugs. Notably, chloroquine activated the mitochondrial cell death pathway as indicated by increase in caspase 9 activity. Interestingly, inhibition of lysosomal proteases using E64 conferred cytoprotection against cisplatin and chloroquine co-treatment, suggesting that chloroquine-induced cell death occurred in a cathepsin-mediated mechanism. Likewise, blockage of caspases partially rescued A549cisR cells against the cytotoxicity of cisplatin and chloroquine combination. Cisplatin promoted a dose-dependent autophagic flux induction preferentially in A549cisR cells, as evidenced by a surge in LC3-II/α-tubulin following pre-treatment with E64 and increase in p62 degradation. Compared to untreated cells, cisplatin induced an increase in cyto-ID-loaded autophagosomes in A549cisR cells that was further amplified by chloroquine, pointing toward autophagic flux activation by cisplatin. Interestingly, this effect

  5. Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Magdalena Circu

    Full Text Available Lung cancer is the leading cause of cancer-related deaths. Most patients develop resistance to platinum within several months of treatment. We investigated whether triggering lysosomal membrane permeabilization (LMP or suppressing autophagy can restore cisplatin susceptibility in lung cancer with acquired chemoresistance. Cisplatin IC50 in A549Pt (parental and A549cisR (cisplatin resistant cells was 13 μM and 47 μM, respectively. Following cisplatin exposure, A549cisR cells failed to elicit an apoptotic response. This was manifested by diminished Annexin-V staining, caspase 3 and 9, BAX and BAK activation in resistant but not in parental cells. Chloroquine preferentially promoted LMP in A549cisR cells, revealed by leakage of FITC-dextran into the cytosol as detected by immunofluorescence microscopy. This was confirmed by increased cytosolic cathepsin D signal on Immunoblot. Cell viability of cisplatin-treated A549cisR cells was decreased when co-treated with chloroquine, corresponding to a combination index below 0.8, suggesting synergism between the two drugs. Notably, chloroquine activated the mitochondrial cell death pathway as indicated by increase in caspase 9 activity. Interestingly, inhibition of lysosomal proteases using E64 conferred cytoprotection against cisplatin and chloroquine co-treatment, suggesting that chloroquine-induced cell death occurred in a cathepsin-mediated mechanism. Likewise, blockage of caspases partially rescued A549cisR cells against the cytotoxicity of cisplatin and chloroquine combination. Cisplatin promoted a dose-dependent autophagic flux induction preferentially in A549cisR cells, as evidenced by a surge in LC3-II/α-tubulin following pre-treatment with E64 and increase in p62 degradation. Compared to untreated cells, cisplatin induced an increase in cyto-ID-loaded autophagosomes in A549cisR cells that was further amplified by chloroquine, pointing toward autophagic flux activation by cisplatin

  6. Pentoxifylline sensitizes human cervical tumor cells to cisplatin-induced apoptosis by suppressing NF-kappa B and decreased cell senescence

    International Nuclear Information System (INIS)

    Hernandez-Flores, Georgina; Bravo-Cuellar, Alejandro; Ortiz-Lazareno, Pablo C; Lerma-Diaz, Jose Manuel; Dominguez-Rodriguez, Jorge R; Jave-Suarez, Luis F; Aguilar-Lemarroy, Adriana del C; Celis-Carrillo, Ruth de; Toro-Arreola, Susana del; Castellanos-Esparza, Yessica C

    2011-01-01

    Worldwide, cervical cancer is the second most common causes of cancer in women and represents an important mortality rate. Cisplatin (CIS) is a very important antitumoral agent and can lead tumor cells toward two important cellular states: apoptosis and senescence. In some types of cancers pentoxifylline (PTX) sensitizes these cells to the toxic action of chemotherapeutics drugs such as adriamycin, inducing apoptosis. In the present work, we studied in vitro whether PTX alone or in combination with CIS induces apoptosis and/or senescence in cervix cancer HeLa and SiHa cell lines infected with HPV types 16 and 18, respectively, as well as in immortalized keratinocytyes HaCaT cells. HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, CIS or both. The cellular toxicity and survival fraction of PTX and CIS were determinate by WST-1 and clonogenic assays respectively. Apoptosis, caspase activation and phosphorylation of ERK1/2, p38, p65 (NF-κB), Bcl-2 and Bcl-XL anti-apoptotic proteins were determinated by flow cytometry. Senescence by microscopy. Phosphorylation of IκBα and IκB total were measured by ELISA. Pro-apoptotic, anti-apoptotic and senescence genes, as well as HPV-E6/7 mRNA expression, were detected by RT-PCR. Our results show that after 24 hours of incubation PTX per se is toxic for cancer cells affecting cell viability and inducing apoptosis. The toxicity in HaCaT cells was minimal. CIS induces apoptosis in HeLa and SiHa cells and its effect was significantly increases when the cells were treated with PTX + CIS. In all studies there was a direct correlation with levels of caspases (-3, -6, -7, -9 and -8) activity and apoptosis. CIS induces important levels of senescence and phosphorylation of ERK1/2, p38, p65/RELA, and IκBα, and decreased the expression of anti-apoptotic protein Bcl-XL. Surprisingly these levels were significantly reduced by PTX in tumor cells, and at the same

  7. Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins.

    Science.gov (United States)

    Pan, Xia; Yang, Xiaoyan; Zang, Jinglei; Zhang, Si; Huang, Nan; Guan, Xinxin; Zhang, Jianhua; Wang, Zhihui; Li, Xi; Lei, Xiaoyong

    2017-06-01

    Overexpression of adenosine triphosphate-binding cassette (ABC) transport protein is emerging as a critical contributor to anticancer drug resistance. The eukaryotic translation initiation factor (eIF) 4F complex, the key modulator of mRNA translation, is regulated by the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway in anticancer drug-resistant tumors. The present study demonstrated the roles of ABC translation protein alterations in the acquisition of the Adriamycin (ADM)-resistant phenotype of MCF-7 human breast cells. Quantitative polymerase chain reaction and western blot analysis were applied to examine the differences in mRNA and protein levels, respectively. It was found that the expression of the ABC sub-family B member 1, ABC sub-family C member 1 and ABC sub-family G member 2 transport proteins were upregulated in MCF-7/ADR cells. An MTT assay was used to detect the cell viability, from the results MCF-7/ADR cells were less sensitive to ADM, tamoxifen (TAM) and taxol (TAX) treatment compared with MCF-7 cells. We predicted that the 3'-untranslated region of eukaryotic translation initiation factor 4-γ 1 (eIF4G) contains a potential miRNA binding site for microRNA (miR)-503 through using computational programs. These binding sites were confirmed by luciferase reporter assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it was demonstrated that eIF4G and ABC translation proteins were significantly downregulated in MCF-7/ADR cells after transfection with miR-503. It was found that miR-503 mimics could sensitize the cells to treatment with ADM, TAM and TAX. These findings demonstrated for the first time that eIF4G acted as a key factor in MCF-7/ADR cells, and may be an efficient agent for preventing and reversing multi-drug resistance in breast cancer.

  8. Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice

    Directory of Open Access Journals (Sweden)

    Go Bouike

    2011-01-01

    Full Text Available To clarify the mechanism of the antiallergic activity of Agaricus blazei Murill extract (ABME, the present paper used an in vivo allergy model and an in vitro intestinal gut model. During OVA sensitization, the serum IgE levels decreased significantly in ABME group. Interleukin (IL-4 and -5 produced from OVA-restimulated splenocytes was significantly decreased, and anti-CD3ε/CD28 antibody treatment also reduced IL-10, -4, and -5 production and increased IFN-γ production in ABME group. These results suggest that oral administration of ABME improves Th1/Th2 balance. Moreover, a coculture system constructed of Caco-2 cells and splenocytes from OT-II mice or RAW 264.7 cells indicated that the significant increases in IFN-γ production by ABME treatment. Therefore, it was concluded that the antiallergic activity of ABME was due to the activation of macrophages by epithelial cells and the promotion of the differentiation of naïve T cells into Th1 cells in the immune.

  9. Contribution of solution pH and buffer capacity to suppress intergranular stress corrosion cracking of sensitized type 304 stainless steel at 95 C

    International Nuclear Information System (INIS)

    Zhang, S.; Shibata, T.; Haruna, T.

    1999-01-01

    Controlling pH of high-temperature water to ∼pH 7 at 300 C by adding lithium hydroxide (LiOH) into the coolant system of a pressurized water reactor (PWR) successfully has been mitigating the corrosion of PWR component materials. The effects of solution pH and buffer capacity on intergranular stress corrosion cracking (IGSCC) of sensitized type 304 stainless steel ([SS] UNS S30400) was examined at 95 C by slow strain rate technique (SSRT) with an in-situ cracking observation system. It was found that an increase in solution pH or buffer capacity increased crack initiation time and decreased mean crack initiation frequency, but exerted almost no effect on crack propagation. This inhibition effect on IGSCC initiation was explained as resulting from a retarding effect of solution pH and buffer capacity on the decrease in pH at crack nuclei caused by the hydrolysis of metal ions dissolved when the passive film was ruptured by strain in SSRT

  10. A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel.

    Science.gov (United States)

    Mato-Berciano, Ana; Raimondi, Giulia; Maliandi, Maria Victoria; Alemany, Ramon; Montoliu, Lluis; Fillat, Cristina

    2017-04-04

    Notch signaling pathway is an embryonic program that becomes reactivated in pancreatic cancer and contributes to cancer stem cell (CSC) maintenance. We explored the concept of oncolytic adenoviral activity in response to Notch activation signaling, in the context of a chimeric promoter with uPAR regulatory sequences, as a strategy to drive its activity in neoplastic and CSC. We explored the advantages of a chemo-virotherapy approach based on synergistic combinations. Regulatory sequences recognized by the transcriptional factor CSL upstream a minimal uPAR promoter were engineered in adenoviral vectors and in the oncolytic adenovirus AdNuPARmE1A. Viral response to Notch signaling, and viral potency in cell lines and pancreatic cancer stem cells (PCSC) was tested. Preclinical toxicity and antitumor efficacy in xenografts and Patient-derived xenografts (PDX) mouse models was evaluated, as unimodal or in combination with gemcitabine+nab-paclitaxel. Mechanistic studies were conducted to explore the synergism of combined therapies.We demonstrate that CSL-binding site optimized-engineered sequences respond to Notch activation in AdNuPARmLuc and AdNuPARmE1A. AdNuPARmE1A showed strong lytic effects in pancreatic cancer cell lines and PCSC. AdNuPARmE1A displayed attenuated activity in normal tissues, but robust antitumor effects in xenograft and PDX models, leading to a reduced capacity of treated tumors to form tumorspheres. Chemo-virotherapy treatment enlarged therapeutic response in both tumor models. Synergistic effects of the combination resulted from viral sensitization of apoptotic cell death triggered by chemotherapy.In summary we present a novel effective oncolytic adenovirus, AdNuPARmE1A that reduces PCSC and presents synergistic effects with gemcitabine and nab-paclitaxel, supporting further clinical development.

  11. Inhibition of T-Type Voltage Sensitive Calcium Channel Reduces Load-Induced OA in Mice and Suppresses the Catabolic Effect of Bone Mechanical Stress on Chondrocytes.

    Directory of Open Access Journals (Sweden)

    Padma P Srinivasan

    Full Text Available Voltage-sensitive calcium channels (VSCC regulate cellular calcium influx, one of the earliest responses to mechanical stimulation in osteoblasts. Here, we postulate that T-type VSCCs play an essential role in bone mechanical response to load and participate in events leading to the pathology of load-induced OA. Repetitive mechanical insult was used to induce OA in Cav3.2 T-VSCC null and wild-type control mouse knees. Osteoblasts (MC3T3-E1 and chondrocytes were treated with a selective T-VSCC inhibitor and subjected to fluid shear stress to determine how blocking of T-VSCCs alters the expression profile of each cell type upon mechanical stimulation. Conditioned-media (CM obtained from static and sheared MC3T3-E1 was used to assess the effect of osteoblast-derived factors on the chondrocyte phenotype. T-VSCC null knees exhibited significantly lower focal articular cartilage damage than age-matched controls. In vitro inhibition of T-VSCC significantly reduced the expression of both early and late mechanoresponsive genes in osteoblasts but had no effect on gene expression in chondrocytes. Furthermore, treatment of chondrocytes with CM obtained from sheared osteoblasts induced expression of markers of hypertrophy in chondrocytes and this was nearly abolished when osteoblasts were pre-treated with the T-VSCC-specific inhibitor. These results indicate that T-VSCC plays a role in signaling events associated with induction of OA and is essential to the release of osteoblast-derived factors that promote an early OA phenotype in chondrocytes. Further, these findings suggest that local inhibition of T-VSCC may serve as a therapy for blocking load-induced bone formation that results in cartilage degeneration.

  12. Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Ibrahim Tekedereli

    Full Text Available Eukaryotic elongation factor 2 kinase (eEF-2K, through its phosphorylation of elongation factor 2 (eEF2, provides a mechanism by which cells can control the rate of the elongation phase of protein synthesis. The activity of eEF-2K is increased in rapidly proliferating malignant cells, is inhibited during mitosis, and may contribute to the promotion of autophagy in response to anti-cancer therapies. The purpose of this study was to examine the therapeutic potential of targeting eEF-2K in breast cancer tumors. Through the systemic administration of liposomal eEF-2K siRNA (twice a week, i.v. 150 µg/kg, the expression of eEF-2K was down-regulated in vivo in an orthotopic xenograft mouse model of a highly aggressive triple negative MDA-MB-231 tumor. This targeting resulted in a substantial decrease in eEF2 phosphorylation in the tumors, and led to the inhibition of tumor growth, the induction of apoptosis and the sensitization of tumors to the chemotherapy agent doxorubicin. eEF-2K down-modulation in vitro resulted in a decrease in the expression of c-Myc and cyclin D1 with a concomitant increase in the expression of p27(Kip1. A decrease in the basal activity of c-Src (phospho-Tyr-416, focal adhesion kinase (phospho-Tyr-397, and Akt (phospho-Ser-473 was also detected following eEF-2K down-regulation in MDA-MB-231 cells, as determined by Western blotting. Where tested, similar results were seen in ER-positive MCF-7 cells. These effects were also accompanied by a decrease in the observed invasive phenotype of the MDA-MB-231 cells. These data support the notion that the disruption of eEF-2K expression in breast cancer cells results in the down-regulation of signaling pathways affecting growth, survival and resistance and has potential as a therapeutic approach for the treatment of breast cancer.

  13. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  14. Deconstructing continuous flash suppression

    OpenAIRE

    Yang, Eunice; Blake, Randolph

    2012-01-01

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

  15. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Mingche [Graduate Institute of Biomedical Materials and Tissue Engineering, College of biomedical engineering, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Urology, School of Medicine, college of Medicine, Taipei Medical University, Taipei, Taiwan (China); Bamodu, Oluwaseun Adebayo [Department of Hematology and Oncology, Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China); Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China); Huang, Wen-Chien [Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan (China); Department of Surgery, Division of Thoracic Surgery, MacKay Memorial Hospital, Taipei, Taiwan (China); Zucha, Muhammad Ary [Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan (China); Lin, Yen-Kuang [Biostatistics and Research Consultation Center, Taipei Medical University, Taipei 11031, Taiwan (China); Wu, Alexander T.H. [The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (China); Huang, Chun-Chih [Center for General Education, National Taitung University, Taitung, Taiwan (China); Lee, Wei-Hwa [Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Yuan, Chiou-Chung [Obstetrics and Gynecology Department, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Hsiao, M. [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China); Deng, Li [Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing (China); Amoy-BUCT Industrial Bio-technovation Institute, Amoy (China); and others

    2017-06-15

    Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy. - Highlights: • Atg-5 is overexpressed in ovarian cancer and silencing Atg-5 induces apoptosis. • 4-AAQB suppresses autophagy and PI3K/Akt/mTOR pathway. • 4-AAQB + cisplatin synergistically suppresses ovarian cancer via

  16. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

    International Nuclear Information System (INIS)

    Liu, Mingche; Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Zucha, Muhammad Ary; Lin, Yen-Kuang; Wu, Alexander T.H.; Huang, Chun-Chih; Lee, Wei-Hwa; Yuan, Chiou-Chung; Hsiao, M.; Deng, Li

    2017-01-01

    Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy. - Highlights: • Atg-5 is overexpressed in ovarian cancer and silencing Atg-5 induces apoptosis. • 4-AAQB suppresses autophagy and PI3K/Akt/mTOR pathway. • 4-AAQB + cisplatin synergistically suppresses ovarian cancer via

  17. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  18. Design and testing of a unique active Compton-suppressed LaBr3(Ce) detector system for improved sensitivity assays of TRU in remote-handled TRU wastes

    Energy Technology Data Exchange (ETDEWEB)

    J. K. Hartwell; M. E. McIlwain; J. A. Kulisek

    2007-10-01

    The US Department of Energy’s transuranic (TRU) waste inventory includes about 4,500 m3 of remote-handled TRU (RH-TRU) wastes composed of a variety of containerized waste forms having a contact surface dose rate that exceeds 2 mSv/hr (200 mrem/hr) containing waste materials with a total TRU concentration greater than 3700 Bq/g (100 nCi/g). As part of a research project to investigate the use of active Compton-suppressed room-temperature gamma-ray detectors for direct non-destructive quantification of the TRU content of these RH-TRU wastes, we have designed and purchased a unique detector system using a LaBr3(Ce) primary detector and a NaI(Tl) suppression mantle. The LaBr3(Ce) primary detector is a cylindrical unit ~25 mm in diameter by 76 mm long viewed by a 38 mm diameter photomultiplier. The NaI(Tl) suppression mantle (secondary detector) is 175 mm by 175 mm with a center well that accommodates the primary detector. An important feature of this arrangement is the lack of any “can” between the primary and secondary detectors. These primary and secondary detectors are optically isolated by a thin layer (.003") of aluminized kapton, but the hermetic seal and thus the aluminum can surrounds the outer boundary of the detector system envelope. The hermetic seal at the primary detector PMT is at the PMT wall. This arrangement virtually eliminates the “dead” material between the primary and secondary detectors, a feature that preliminary modeling indicated would substantially improve the Compton suppression capability of this device. This paper presents both the expected performance of this unit determined from modeling with MCNPX, and the performance measured in our laboratory with radioactive sources.

  19. Vasomotor response to cold stimulation in human capsaicin-induced hyperalgesic area.

    Science.gov (United States)

    Pud, Dorit; Andersen, Ole Kaeseler; Arendt-Nielsen, Lars; Eisenberg, Elon; Yarnitsky, David

    2005-07-01

    Cooling the skin induces sympathetically driven vasoconstriction, with some vasoparalytic dilatation at the lowest temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In this study we investigated the balance between vasoconstriction and vasodilatation in an area of experimentally induced secondary hyperalgesia (2 degrees HA), in response to low-temperature stimulations. Fourteen healthy volunteers were exposed to three 30-s long cold stimuli (20, 10, and 0 degrees C) applied, at three adjacent sites, before (baseline) and 8 min after intradermal injection of 50 microg capsaicin to the volar forearm. The cold stimuli were applied distally to the injection site within the 2 degrees HA. Blood flux (BF) and skin temperatures were measured at four different regions (proximally, and distally to the capsaicin injection and at the 0, 10, and 20 degrees C thermode sites) all within the 2 degrees HA. The vascular measurements were conducted five times. Results showed a marked increase in BF after baseline cold stimulation (Peffect (elevated BF) was found following the capsaicin injection compared with baseline for all regions (Pcooled area was dilated by 450+/-5.1%; The vasoconstrictive effect for the 10 and 20 degrees C did not overcome the capsaicin vasodilatation, but did reduce it, with dilatation of 364+/-7.0% and 329+/-7.3%, respectively. For 0 degrees C, a dilatation of 407+/-6.5% was seen. It is concluded that in this experimental model, and potentially in the equivalent clinical syndromes, vasodilatation induced by the inflammation is only slightly reduced by cold stimulation such that it is still dominant, despite some cold-induced vasoconstriction.

  20. Capsaicin induced histological and ultrastructural changes in the submandibular salivary gland of albino rats

    Directory of Open Access Journals (Sweden)

    Ahmed Mahmoud Halawa

    2016-06-01

    From the present work, it could be concluded that chronic capsaicin intake was associated with noticeable histological and ultrastructural changes in acini, granular convoluted tubules and excretory ducts of the SMSG in albino rats.

  1. Increase in swimming endurance capacity of mice by capsaicin-induced adrenal catecholamine secretion.

    Science.gov (United States)

    Kim, K M; Kawada, T; Ishihara, K; Inoue, K; Fushiki, T

    1997-10-01

    Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60 min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.

  2. Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Ricardo Ramírez-Barrantes

    2018-06-01

    Full Text Available The transient receptor potential (TRP ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV family have been directly implicated in cell death. TRPV1 is activated by pain-inducing stimuli, including inflammatory endovanilloids and pungent exovanilloids, such as capsaicin (CAP. TRPV1 activation by high doses of CAP (>10 μM leads to necrosis, but also exhibits apoptotic characteristics. However, CAP dose–response studies are lacking in order to determine whether CAP-induced cell death occurs preferentially via necrosis or apoptosis. In addition, it is not known whether cytosolic Ca2+ and mitochondrial dysfunction participates in CAP-induced TRPV1-mediated cell death. By using TRPV1-transfected HeLa cells, we investigated the underlying mechanisms involved in CAP-induced TRPV1-mediated cell death, the dependence of CAP dose, and the participation of mitochondrial dysfunction and cytosolic Ca2+ increase. Together, our results contribute to elucidate the pathophysiological steps that follow after TRPV1 stimulation with CAP. Low concentrations of CAP (1 μM induce cell death by a mechanism involving a TRPV1-mediated rapid and transient intracellular Ca2+ increase that stimulates plasma membrane depolarization, thereby compromising plasma membrane integrity and ultimately leading to cell death. Meanwhile, higher doses of CAP induce cell death via a TRPV1-independent mechanism, involving a slow and persistent intracellular Ca2+ increase that induces mitochondrial dysfunction, plasma membrane depolarization, plasma membrane loss of integrity, and ultimately, cell death.

  3. Adiabatic Low-Pass J Filters for Artifact Suppression in Heteronuclear NMR

    DEFF Research Database (Denmark)

    Meier, Sebastian; Benie, Andrew J; Duus, Jens Øllgaard

    2009-01-01

    NMR artifact purging: Modern NMR experiments depend on efficient coherence transfer pathways for their sensitivity and on suppression of undesired pathways leading to artifacts for their spectral clarity. A novel robust adiabatic element suppresses hard-to-get-at artifacts....

  4. Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2018-04-01

    Full Text Available Proopiomelanocortin (POMC neurons in the arcuate nucleus of the hypothalamus (ARC respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR, immunohistochemistry, electrophysiology, TRPV1 knock-out (KO, and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5 carrying a Cre-dependent channelrhodopsin-2 (ChR2-enhanced yellow fluorescent protein (eYFP expression cassette under the control of the two neuronal POMC enhancers (nPEs. Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.

  5. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system.

    Science.gov (United States)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik; Hallén, Anna; Bäckhed, Fredrik; Jansson, John-Olov

    2013-10-01

    The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.

  6. Sodium fire suppression

    Energy Technology Data Exchange (ETDEWEB)

    Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

    1979-03-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  7. Sodium fire suppression

    International Nuclear Information System (INIS)

    Malet, J.C.

    1979-01-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  8. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

    International Nuclear Information System (INIS)

    Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

    2016-01-01

    Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

  9. Pressure suppression device

    International Nuclear Information System (INIS)

    Mizumachi, Wataru; Fukuda, Akira; Kitaguchi, Hidemi; Shimizu, Toshiaki.

    1976-01-01

    Object: To relieve and absorb impact wave vibrations caused by steam and non-condensed gases releasing into the pressure suppression chamber at the time of an accident. Structure: The reactor container is filled with inert gases. A safety valve attached main steam pipe is provided to permit the excessive steam to escape, the valve being communicated with the pressure suppression chamber through an exhaust pipe. In the pressure suppression chamber, a doughnut-like cylindrical outer wall is filled at its bottom with pool water to condense the high temperature vapor released through the exhaust pipe. A head portion of a vent tube which leads the exhaust pipe is positioned at the top, and a down comer and an exhaust vent tube are locked by means of steady rests. At the bottom is mounted a pressure adsorber device which adsorbs a pressure from the pool water. (Kamimura, M.)

  10. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    International Nuclear Information System (INIS)

    Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

    2011-01-01

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  11. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2011-02-15

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  12. Thyroxin hormone suppression treatment

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

  13. Pressure suppressing device

    International Nuclear Information System (INIS)

    Naito, Makoto.

    1980-01-01

    Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

  14. Suppressed Charmed B Decay

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, Hella Leonie [Vrije Univ., Amsterdam (Netherlands)

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  15. J/Ψ suppression

    International Nuclear Information System (INIS)

    Giubellino, P.; Abreu, M.C.; Alessandro, B.; Alexa, C.; Arnaldi, R.; Astruc, J.; Atayan, M.; Baglin, C.; Baldit, A.; Bedjidian, M.; Bellaiche, F.; Beole, S.; Boldea, V.; Bordalo, P.; Bussiere, A.; Capony, V.; Casagrande, L.; Castor, J.; Chambon, T.; Chaurand, B.; Chevrot, I.; Cheynis, B.; Chiavassa, E.; Cicalo, C.; Comets, M.P.; Constantinescu, S.; Cruz, J.; De Falco, A.; De Marco, N.; Dellacasa, G.; Devaux, A.; Dita, S.; Drapier, O.; Espagnon, B.; Fargeix, J.; Filippov, S.N.; Fleuret, F.; Force, P.; Gallio, M.; Gavrilov, Y.K.; Gerschel, C.; Giubellino, P.; Golubeva, M.B.; Gonin, M.; Grigorian, A.A.; Grossiord, J.Y.; Guber, F.F.; Guichard, A.; Gulkaninan, H.; Hakobyan, R.; Haroutunian, R.; Idzik, M.; Jouan, D.; Karavitcheva, T.L.; Kluberg, L.; Kurepin, A.B.; Le Bornec, Y.; Lourenco, C.; Mac Cormick, M.; Macciotta, P.; Marzari-Chiesa, A.; Masera, M.; Masoni, A.; Mehrabyan, S.; Mourgues, S.; Musso, A.; Ohlsson-Malek, F.; Petiau, P.; Piccotti, A.; Pizzi, J.R.; Prado da Silva, W.L.; Puddu, G.; Quintans, C.; Racca, C.; Ramello, L.; Ramos, S.; Rato-Mendes, P.; Riccati, L.; Romana, A.; Sartori, S.; Saturnini, P.; Scomparin, E.; Serci, S.; Shahoyan, R.; Silva, S.; Soave, C.; Sonderegger, P.; Tarrago, X.; Temnikov, P.; Topilskaya, N.S.; Usai, G.; Vale, C.; Vercellin, E.; Willis, N.

    1999-01-01

    The cross section for J/Ψ production in Pb-Pb interactions at 158 GeV per nucleon is measured at the CERN SPS by the NA50 experiment. The final results from the 1995 run are presented here together with preliminary ones from the high-statistics 1996 run. An anomalous J/Ψ suppression is observed in Pb-Pb collisions as compared to extrapolations of the previous results obtained by the NA38 experiment with proton and lighter ion beams. The results of the two runs are in good agreement. The results from the 1996 run allow the study of the onset of the anomalous suppression within the same set of data, showing evidence of a sharp change of behaviour around a value of neutral transverse energy, as measured by our electromagnetic calorimeter, of about 50 GeV

  16. The pressure suppression system

    International Nuclear Information System (INIS)

    Aust, E.

    1985-01-01

    Nuclear plants with boiling water reactors have a safety containment with a pressure suppression system (PSS). Proceeding on significant self-developments, today the three PSS-lines of General Electric Co. (GE), Kraftwerk Union AG (KWU) and ASEA-ATOM are predominant, which are currently represented by the MARK III type, the KWU type 72 and the BWR 75 containment. In addition, there are special developments for the nuclear ship propulsion and for the pressurized water reactors in the Soviet Union. Key design values of the PSS allow a first valuation of its loads during a hypothetical loss-of-coolant accident. (orig.) [de

  17. Radiation effluent suppression system

    International Nuclear Information System (INIS)

    Watanabe, Atsushi.

    1992-01-01

    In a radiation release suppression system upon accident, an electromotive valve, a pneumatic operation valve or a manual operation valve is disposed to gas ventilation pipelines which are extended from both of a dry well and a wet well of a reactor container to a stuck. In addition, a combination filter of a metal fiber filter made of stainless steel etc. and an activated carbon fiber filter is disposed in the midway of pipelines in a reactor building. With such a constitution, the inside of the container can be depressurized (prevention of ruptures) and the amount of radioactive substances released to circumstances is remarkably suppressed by the effect of radioactive substance capturing effect of the metal fiber filter made of stainless steel etc. disposed in the vent pipe in the container and a radioactive substance capturing effect by the combination filter of the metal fiber filter made of stainless steel, etc. and the activated carbon fiber filter disposed in the gas ventilation pipelines even upon occurrence of an accident exceeding design basis. Systems can be simplified and minimized, and cost down can also be attained. (N.H.)

  18. Planck-suppressed operators

    International Nuclear Information System (INIS)

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10 5 H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10 2 H

  19. Growth Suppression and Therapy Sensitization of Breast Cancer

    Science.gov (United States)

    2001-07-01

    performed on two independent occasions. PCR amplification of a given housekeeping gene have been shown to correspond to determinations of platination...dI **i𔃾 A NK U S P.UDjl G3PDH Figure 9. A549 cells were treated with 3 different antisense oligonucleotides complementary to JNKl mRNA (including...northern analysis, the same membrane was hybridized successively with JNKI probe, JNK2 probe and the G3PDH probe. (see Reed, 1998 for review), which

  20. Theoretical status of J/ψ suppression

    International Nuclear Information System (INIS)

    Gavin, S.

    1993-03-01

    High energy heavy ion collisions are expected to produce hadron densities far beyond the density in nuclei, ρ 0 = 0.16 fm -3 . Remarkably, no single measurement from the AGS and SPS light ion programs with projectiles A ≤ 32 stands out as unambiguous evidence of these extreme densities. To separate the high density signals from the background effects that result, e.g. from scattering with primary nucleons, careful systematic studies of hadron-nucleus, hA, and nucleus-nucleus, AB, data are needed. In this talk the author surveys the ongoing systematic study of the most notorious case in point -- J/ψ suppression. In principle, measurements of J/ψ suppression provide a probe of the densities obtained in AB collisions that is also sensitive to quark gluon plasma production. The latest results from SPS experiment NA38 reported by A. Romana in these proceedings show that the ratio of cross sections in the dimuon channel B μμ σ ψ /σ cont is reduced by a factor 0.50 ± 0.05 in central S+U compared to minimum bias pU collisions at 200 AGeV. This is precisely the sort of suppression that one expects if high densities are obtained. On the other hand, a target-mass dependence suggestive of this suppression is found in hA collisions where high densities are not expected. At 200 GeV, NA38 finds that B μμ σ ψ /σ cont falls to 0.84 ± 0.08 in pU compared to pCu. The hA suppression in this kinematic regime is likely due to a combination of nuclear effects: nucleon absorption and shadowing

  1. Screening for suppression in young children: the Polaroid Suppression test

    NARCIS (Netherlands)

    Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

    1998-01-01

    Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

  2. Sensitivity analysis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  3. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

    Science.gov (United States)

    Leung, Felix W

    2008-07-04

    This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

  4. Acetonitrile Ion Suppression in Atmospheric Pressure Ionization Mass Spectrometry

    Science.gov (United States)

    Colizza, Kevin; Mahoney, Keira E.; Yevdokimov, Alexander V.; Smith, James L.; Oxley, Jimmie C.

    2016-11-01

    Efforts to analyze trace levels of cyclic peroxides by liquid chromatography/mass spectrometry gave evidence that acetonitrile suppressed ion formation. Further investigations extended this discovery to ketones, linear peroxides, esters, and possibly many other types of compounds, including triazole and menadione. Direct ionization suppression caused by acetonitrile was observed for multiple adduct types in both electrospray ionization and atmospheric pressure chemical ionization. The addition of only 2% acetonitrile significantly decreased the sensitivity of analyte response. Efforts to identify the mechanism were made using various nitriles. The ion suppression was reduced by substitution of an acetonitrile hydrogen with an electron-withdrawing group, but was exacerbated by electron-donating or steric groups adjacent to the nitrile. Although current theory does not explain this phenomenon, we propose that polar interactions between the various functionalities and the nitrile may be forming neutral aggregates that manifest as ionization suppression.

  5. Subjective duration distortions mirror neural repetition suppression.

    Science.gov (United States)

    Pariyadath, Vani; Eagleman, David M

    2012-01-01

    Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  6. Pressure suppression device

    International Nuclear Information System (INIS)

    Yoshida, Toyokazu.

    1976-01-01

    Purpose: To provide a pressure suppression device for a gas cooled reactor wherein the coolant is discharged in a reactor building by a loss-of-coolant accident or the like, the increase in the pressure and temperature is controlled and thermal energy of the discharged coolant of high temperature and high pressure can be absorbed. Constitution: A low heat source unit is provided at the upper part in an inner space of a reactor building provided around the reactor, and at the upper part of the low heat source unit a stirring fan for mixing gas within the building, and a low heat source circulating the low heat source through a pipe is connected to the low heat source unit. The low heat source unit is provided with the pipe arranged in a spiral shape at the upper part of the space of the unit, and a large number of fins are provided at the outer surface of the pipe for increasing the transmission area and improve the heat exchange. When the coolant of high temperature and high pressure has been lost in the building, the thermal energy of the coolant is absorbed by the low heat source unit. (Aizawa, K.)

  7. Fast, fat-suppressed diagnostic imaging of the breast

    International Nuclear Information System (INIS)

    Metzger, G.J.; Weatherall, P.

    1999-01-01

    Maximum sensitivity and diagnostic precision of MR imaging of the breast can be achieved only with fat-suppressed diagnostic scans with high resolution. Optimal results were obtained with a 3D-FFE sequence and excitation by a binomial pulse and an amplitude-modulated binomial pulse. (orig./CB) [de

  8. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-α2 and -α3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this co...

  9. Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-01-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p.o., glutamate NMDA receptor (DL-AP5, 10 μg/site, i.t., substance P NK-1 receptor (RP-67580, 10 μg/site, i.t. and nitric oxide synthase (L-NNA, 10 μg/site, i.t.. The B1R fluorescent agonist was co-localized with an immunomarker of microglia (Iba-1 in spinal cord dorsal horn of capsaicin-treated rats. Conclusion This study highlights a new mechanism for B1R induction via TRPV1 activation and establishes a link between these two pro-nociceptive receptors in inflammatory pain.

  10. Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

    Directory of Open Access Journals (Sweden)

    Fatemeh Esfahanian

    2010-08-01

    Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

  11. Allergic sensitization

    DEFF Research Database (Denmark)

    van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased pe...

  12. Compton suppression gamma ray spectrometry

    International Nuclear Information System (INIS)

    Landsberger, S.; Iskander, F.Y.; Niset, M.; Heydorn, K.

    2002-01-01

    In the past decade there have been many studies to use Compton suppression methods in routine neutron activation analysis as well as in the traditional role of low level gamma ray counting of environmental samples. On a separate path there have been many new PC based software packages that have been developed to enhance photopeak fitting. Although the newer PC based algorithms have had significant improvements, they still suffer from being effectively used in weak gamma ray lines in natural samples or in neutron activated samples that have very high Compton backgrounds. We have completed a series of experiments to show the usefulness of Compton suppression. As well we have shown the pitfalls when using Compton suppression methods for high counting deadtimes as in the case of neutron activated samples. We have also investigated if counting statistics are the same both suppressed and normal modes. Results are presented in four separate experiments. (author)

  13. Thyroid suppression test with dextrothyroxine

    International Nuclear Information System (INIS)

    Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

    1978-01-01

    The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

  14. Climate Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lindzen, Richard [M.I.T.

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  15. Expressive suppression and neural responsiveness to nonverbal affective cues.

    Science.gov (United States)

    Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

    2015-10-01

    Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

  16. Serum thyrotropin (TSH) levels in patients with suppressed pituitary function

    International Nuclear Information System (INIS)

    Vasavada, P.; Chen, I.; Maxon, H.; Barnes, E.; Sperling, M.

    1984-01-01

    The diagnosis of borderline hyperthyroidism is difficult. A sensitive radioimmunoassay capable of detecting subnormal levels of serum TSH may be of value in confirming this diagnosis because of the suppressed pituitary function in this disease state. This sensitive assay may also be useful in monitoring the suppression of pituitary function in thyroid cancer patients receiving thyroid hormone therapy. A sensitive radioimmunoassay capable of detecting serum TSH levels as low as 0.25 μU/m1 with coefficients of variation less than 17.2% was used to measure serum TSH levels in 80 healthy subjects, 44 hyperthyroid patients, and 25 athyrotic thyroid cancer patients on daily suppressive doses of thyroxine. All healthy subjects had detectable TSH levels with a mean value of 1.17 and two standard deviation ranges of 0.41 - 2.70 μU/m1 (lognormal distribution). Although the mean +-1 SEM value of 0.63 +- 0.003 μUm1 for hyperthyroid patients and 0.76 +- 0.08 μU/ml for thyroid cancer patients were significantly lower than that of healthy subjects (t-test, p<0.05), subnormal levels of serum TSH were found in only 28.6% (12/42) and 24% (6/25) of hyperthyroid and thyroid cancer patients, respectively. TSH stimulation tests performed in 6 of the cancer patients all gave suppressed responses. Because of considerable overlap, serum TSH levels alone cannot distinguish hyperthyroidsm from euthyroidism. However, a sensitive TSH radioimmunoassay such as the one described here may be of value in evaluating the extent of pituitary suppression in thyroid cancer therapy

  17. Radioecological sensitivity

    International Nuclear Information System (INIS)

    Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

    2003-01-01

    After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

  18. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    International Nuclear Information System (INIS)

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

    2014-01-01

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4 + T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4 + T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects

  19. Clinical classification of suppressed and low normal basal serum TSH concentrations in euthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, C.; Ziegelitz, D.; Correns, H.J.

    1981-02-01

    By use of highly sensitive and accurate TSH radioimmunoassay it can be shown that beginning with suppressed TSH-levels in serum during increasing TSH-levels TSH response after TRH injection increases concomitantly, i.e. there is positive correlation between basal TSH and TSH response after TRH. TRH mediated TSH-increase shows positive correlation to thyroidal suppressibility with thyroid hormones. The results demonstrate the importance of a highly sensitive and accurate TSH radioimmunoassay for clinical work especially for exclusion of hyperthyroidism or thyroidal autonomy for therapeutics of goiter, prevention of reoccurring goiter and control of thyroidal suppression.

  20. Subjective duration distortions mirror neural repetition suppression.

    Directory of Open Access Journals (Sweden)

    Vani Pariyadath

    Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  1. Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

    Science.gov (United States)

    Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

    2014-07-01

    Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

  2. Stimulus-dependent suppression of chaos in recurrent neural networks

    International Nuclear Information System (INIS)

    Rajan, Kanaka; Abbott, L. F.; Sompolinsky, Haim

    2010-01-01

    Neuronal activity arises from an interaction between ongoing firing generated spontaneously by neural circuits and responses driven by external stimuli. Using mean-field analysis, we ask how a neural network that intrinsically generates chaotic patterns of activity can remain sensitive to extrinsic input. We find that inputs not only drive network responses, but they also actively suppress ongoing activity, ultimately leading to a phase transition in which chaos is completely eliminated. The critical input intensity at the phase transition is a nonmonotonic function of stimulus frequency, revealing a 'resonant' frequency at which the input is most effective at suppressing chaos even though the power spectrum of the spontaneous activity peaks at zero and falls exponentially. A prediction of our analysis is that the variance of neural responses should be most strongly suppressed at frequencies matching the range over which many sensory systems operate.

  3. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  4. Obtuse triangle suppression in anisotropic meshes

    KAUST Repository

    Sun, Feng; Choi, Yi King; Wang, Wen Ping; Yan, Dongming; Liu, Yang; Lé vy, Bruno L.

    2011-01-01

    Anisotropic triangle meshes are used for efficient approximation of surfaces and flow data in finite element analysis, and in these applications it is desirable to have as few obtuse triangles as possible to reduce the discretization error. We present a variational approach to suppressing obtuse triangles in anisotropic meshes. Specifically, we introduce a hexagonal Minkowski metric, which is sensitive to triangle orientation, to give a new formulation of the centroidal Voronoi tessellation (CVT) method. Furthermore, we prove several relevant properties of the CVT method with the newly introduced metric. Experiments show that our algorithm produces anisotropic meshes with much fewer obtuse triangles than using existing methods while maintaining mesh anisotropy. © 2011 Elsevier B.V. All rights reserved.

  5. Obtuse triangle suppression in anisotropic meshes

    KAUST Repository

    Sun, Feng

    2011-12-01

    Anisotropic triangle meshes are used for efficient approximation of surfaces and flow data in finite element analysis, and in these applications it is desirable to have as few obtuse triangles as possible to reduce the discretization error. We present a variational approach to suppressing obtuse triangles in anisotropic meshes. Specifically, we introduce a hexagonal Minkowski metric, which is sensitive to triangle orientation, to give a new formulation of the centroidal Voronoi tessellation (CVT) method. Furthermore, we prove several relevant properties of the CVT method with the newly introduced metric. Experiments show that our algorithm produces anisotropic meshes with much fewer obtuse triangles than using existing methods while maintaining mesh anisotropy. © 2011 Elsevier B.V. All rights reserved.

  6. Aging and repeated thought suppression success.

    Directory of Open Access Journals (Sweden)

    Ann E Lambert

    Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  7. Accentuation-suppression and scaling

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik; Bundesen, Claus

    2012-01-01

    The limitations of the visual short-term memory (VSTM) system have become an increasingly popular field of study. One line of inquiry has focused on the way attention selects objects for encoding into VSTM. Using the framework of the Theory of Visual Attention (TVA; Bundesen, 1990 Psychological...... a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...

  8. Breaking continuous flash suppression: A new measure of unconscious processing during interocular suppression?

    Directory of Open Access Journals (Sweden)

    Timo eStein

    2011-12-01

    Full Text Available Until recently, it has been thought that under interocular suppression high-level visual processing is strongly inhibited if not abolished. With the development of continuous flash suppression (CFS, a variant of binocular rivalry, this notion has now been challenged by a number of reports showing that even high-level aspects of visual stimuli, such as familiarity, affect the time stimuli need to overcome CFS and emerge into awareness. In this breaking CFS (b-CFS paradigm, differential unconscious processing during suppression is inferred when (a speeded detection responses to initially invisible stimuli differ, and (b no comparable differences are found in non-rivalrous control conditions supposed to measure general threshold differences between stimuli. To critically evaluate these assumptions was the aim of the present study. In six experiments we compared the time upright and inverted faces needed to be detected. We found that not only under CFS, but also in control conditions upright faces were detected faster and more accurately than inverted faces, although the effect was larger during CFS. However, reaction time (RT distributions indicated critical differences between the CFS and the control condition. When RT distributions were matched, similar effect sizes were obtained in both conditions. Moreover, subjective ratings revealed that CFS and control conditions are not perceptually comparable. These findings cast doubt on the usefulness of non-rivalrous control conditions to rule out mere detection threshold differences as a cause of shorter detection latencies during CFS. In conclusion, we acknowledge that the b-CFS paradigm can be fruitfully applied as a highly sensitive device to probe differences between stimuli in their potency to gain access to awareness. However, our current findings suggest that such differences can not unequivocally be attributed to differential unconscious processing under interocular suppression.

  9. Differences in xylogenesis between dominant and suppressed trees.

    Science.gov (United States)

    Liu, Shushan; Li, Xiaoxia; Rossi, Sergio; Wang, Lily; Li, Wei; Liang, Eryuan; Leavitt, Steven W

    2018-05-01

    Most dendroecological studies focus on dominant trees, but little is known about the growing season of trees belonging to different size classes and their sensitivity to biotic factors. The objective of this study was to compare the dynamics of xylem formation between dominant and suppressed trees of Abies fabri of similar age growing in the Gongga Mountains, southeastern Tibetan Plateau, and to identify the association between xylem growth and climate. The timing and duration of xylogenesis in histological sections were investigated weekly during the 2013-2015 growing seasons. Our investigation found that timing and duration of xylogenesis varied with canopy position and its associated tree size. Xylogenesis started 6-14 days earlier, and ended 5-11 days later in dominant trees than in suppressed trees, resulting in a significantly longer growing season. Dominant trees also exhibited higher temperature sensitivity of tracheid production rate than suppressed trees. The observed differences in xylogenesis among trees suggested that competition affects tree growth by reducing the growing period in suppressed trees. Representative climate-growth relationships should involve trees of all size classes when evaluating the effects of the environment on forest dynamics. © 2018 Botanical Society of America.

  10. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    International Nuclear Information System (INIS)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system

  11. Distinguishing among potential mechanisms of singleton suppression.

    Science.gov (United States)

    Gaspelin, Nicholas; Luck, Steven J

    2018-04-01

    Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  12. Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

    NARCIS (Netherlands)

    Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

    The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

  13. Sensitive Media

    Directory of Open Access Journals (Sweden)

    Malinowska Anna

    2017-12-01

    Full Text Available The paper engages with what we refer to as “sensitive media,” a concept associated with developments in the overall media environment, our relationships with media devices, and the quality of the media themselves. Those developments point to the increasing emotionality of the media world and its infrastructures. Mapping the trajectories of technological development and impact that the newer media exert on human condition, our analysis touches upon various forms of emergent affect, emotion, and feeling in order to trace the histories and motivations of the sensitization of “the media things” as well as the redefinition of our affective and emotional experiences through technologies that themselves “feel.”

  14. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  15. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  16. Suppression of stratified explosive interactions

    Energy Technology Data Exchange (ETDEWEB)

    Meeks, M.K.; Shamoun, B.I.; Bonazza, R.; Corradini, M.L. [Wisconsin Univ., Madison, WI (United States). Dept. of Nuclear Engineering and Engineering Physics

    1998-01-01

    Stratified Fuel-Coolant Interaction (FCI) experiments with Refrigerant-134a and water were performed in a large-scale system. Air was uniformly injected into the coolant pool to establish a pre-existing void which could suppress the explosion. Two competing effects due to the variation of the air flow rate seem to influence the intensity of the explosion in this geometrical configuration. At low flow rates, although the injected air increases the void fraction, the concurrent agitation and mixing increases the intensity of the interaction. At higher flow rates, the increase in void fraction tends to attenuate the propagated pressure wave generated by the explosion. Experimental results show a complete suppression of the vapor explosion at high rates of air injection, corresponding to an average void fraction of larger than 30%. (author)

  17. Strangeness Suppression and Color Deconfinement

    Science.gov (United States)

    Satz, Helmut

    2018-02-01

    The relative multiplicities for hadron production in different high energy collisions are in general well described by an ideal gas of all hadronic resonances, except that under certain conditions, strange particle rates are systematically reduced. We show that the suppression factor γs, accounting for reduced strange particle rates in pp, pA and AA collisions at different collision energies, becomes a universal function when expressed in terms of the initial entropy density s0 or the initial temperature T of the produced thermal medium. It is found that γs increases from about 0.5 to 1.0 in a narrow temperature range around the quark-hadron transition temperature Tc ≃ 160 MeV. Strangeness suppression thus disappears with the onset of color deconfinement; subsequently, full equilibrium resonance gas behavior is attained.

  18. Chk1 suppressed cell death

    Directory of Open Access Journals (Sweden)

    Meuth Mark

    2010-09-01

    Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

  19. Sensitive Ceramics

    DEFF Research Database (Denmark)

    2014-01-01

    Sensitive Ceramics is showing an interactive digital design tool for designing wall like composition with 3d ceramics. The experiment is working on two levels. One which has to do with designing compositions and patterns in a virtual 3d universe based on a digital dynamic system that responds on ...... with realizing the modules in ceramics by 3d printing directly in porcelain with a RapMan printer that coils up the 3d shape in layers. Finally the ceramic modules are mounted in a laser cut board that reflects the captured composition of the movement of the hands....

  20. In-Flight Suppressant Deployment Temperatures

    National Research Council Canada - National Science Library

    Bein, Donald

    2006-01-01

    .... An assessment is made of the model output versus some aircraft measurement data, fire suppressant boiling point criterion, as well as the history of altitude/temperature at which fire suppressants have been deployed...

  1. In the suppression of regge cut contributions

    International Nuclear Information System (INIS)

    Chia, S.P.

    1975-07-01

    It is shown that contributions of reggeon-pomeron cuts are suppressed in amplitudes with opposite natural to the reggeon. This suppression grows logarithmically with energy. The suppression in the πP cut is, however, found to be weak. Consequence on conspiracy is discussed

  2. Optimization of Compton-suppression and summing schemes for the TIGRESS HPGe detector array

    Science.gov (United States)

    Schumaker, M. A.; Svensson, C. E.; Andreoiu, C.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Boston, A. J.; Chakrawarthy, R. S.; Churchman, R.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hyland, B.; Jones, B.; Maharaj, R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Sarazin, F.; Scraggs, H. C.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.

    2007-04-01

    Methods of optimizing the performance of an array of Compton-suppressed, segmented HPGe clover detectors have been developed which rely on the physical position sensitivity of both the HPGe crystals and the Compton-suppression shields. These relatively simple analysis procedures promise to improve the precision of experiments with the TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS). Suppression schemes will improve the efficiency and peak-to-total ratio of TIGRESS for high γ-ray multiplicity events by taking advantage of the 20-fold segmentation of the Compton-suppression shields, while the use of different summing schemes will improve results for a wide range of experimental conditions. The benefits of these methods are compared for many γ-ray energies and multiplicities using a GEANT4 simulation, and the optimal physical configuration of the TIGRESS array under each set of conditions is determined.

  3. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

    Science.gov (United States)

    Xiao, Y; Guan, J

    2015-01-01

    Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

  4. Comparative study of fat-suppression techniques for hip arthroplasty MR imaging.

    Science.gov (United States)

    Molière, Sébastien; Dillenseger, Jean-Philippe; Ehlinger, Matthieu; Kremer, Stéphane; Bierry, Guillaume

    2017-09-01

    The goal of this study was to evaluate different fat-suppressed fluid-sensitive sequences in association with different metal artifacts reduction techniques (MARS) to determine which combination allows better fat suppression around metallic hip implants. An experimental study using an MRI fat-water phantom quantitatively evaluated contrast shift induced by metallic hip implant for different fat-suppression techniques and MARS. Then a clinical study with patients addressed to MRI unit for painful hip prosthesis compared these techniques in terms of fat suppression quality and diagnosis confidence. Among sequences without MARS, both T2 Dixon and short tau inversion recuperation (STIR) had significantly lower contrast shift (p < 0.05), Dixon offering the best fat suppression. Adding MARS (view-angle tilting or slice-encoding for metal artifact correction (SEMAC)) to STIR gave better results than Dixon alone, and also better than SPAIR and fat saturation with MARS (p < 0.05). There were no statistically significant differences between STIR with view-angle tilting and STIR with SEMAC in terms of fat suppression quality. STIR sequence is the preferred fluid-sensitive MR sequence in patients with metal implant. In combination with MARS (view-angle tilting or SEMAC), STIR appears to be the best option for high-quality fat suppression.

  5. Comparative study of fat-suppression techniques for hip arthroplasty MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moliere, Sebastien [University Hospital of Strasbourg, Imaging Department, Strasbourg (France); Dillenseger, Jean-Philippe; Kremer, Stephane; Bierry, Guillaume [University Hospital of Strasbourg, Imaging Department, Strasbourg (France); ICube UMR 7357, University of Strasbourg, Strasbourg (France); Ehlinger, Matthieu [ICube UMR 7357, University of Strasbourg, Strasbourg (France); University Hospital of Strasbourg, Orthopaedic Department, Strasbourg (France)

    2017-09-15

    The goal of this study was to evaluate different fat-suppressed fluid-sensitive sequences in association with different metal artifacts reduction techniques (MARS) to determine which combination allows better fat suppression around metallic hip implants. An experimental study using an MRI fat-water phantom quantitatively evaluated contrast shift induced by metallic hip implant for different fat-suppression techniques and MARS. Then a clinical study with patients addressed to MRI unit for painful hip prosthesis compared these techniques in terms of fat suppression quality and diagnosis confidence. Among sequences without MARS, both T2 Dixon and short tau inversion recuperation (STIR) had significantly lower contrast shift (p < 0.05), Dixon offering the best fat suppression. Adding MARS (view-angle tilting or slice-encoding for metal artifact correction (SEMAC)) to STIR gave better results than Dixon alone, and also better than SPAIR and fat saturation with MARS (p < 0.05). There were no statistically significant differences between STIR with view-angle tilting and STIR with SEMAC in terms of fat suppression quality. STIR sequence is the preferred fluid-sensitive MR sequence in patients with metal implant. In combination with MARS (view-angle tilting or SEMAC), STIR appears to be the best option for high-quality fat suppression. (orig.)

  6. Comparative study of fat-suppression techniques for hip arthroplasty MR imaging

    International Nuclear Information System (INIS)

    Moliere, Sebastien; Dillenseger, Jean-Philippe; Kremer, Stephane; Bierry, Guillaume; Ehlinger, Matthieu

    2017-01-01

    The goal of this study was to evaluate different fat-suppressed fluid-sensitive sequences in association with different metal artifacts reduction techniques (MARS) to determine which combination allows better fat suppression around metallic hip implants. An experimental study using an MRI fat-water phantom quantitatively evaluated contrast shift induced by metallic hip implant for different fat-suppression techniques and MARS. Then a clinical study with patients addressed to MRI unit for painful hip prosthesis compared these techniques in terms of fat suppression quality and diagnosis confidence. Among sequences without MARS, both T2 Dixon and short tau inversion recuperation (STIR) had significantly lower contrast shift (p < 0.05), Dixon offering the best fat suppression. Adding MARS (view-angle tilting or slice-encoding for metal artifact correction (SEMAC)) to STIR gave better results than Dixon alone, and also better than SPAIR and fat saturation with MARS (p < 0.05). There were no statistically significant differences between STIR with view-angle tilting and STIR with SEMAC in terms of fat suppression quality. STIR sequence is the preferred fluid-sensitive MR sequence in patients with metal implant. In combination with MARS (view-angle tilting or SEMAC), STIR appears to be the best option for high-quality fat suppression. (orig.)

  7. Polypyrrole Actuators for Tremor Suppression

    DEFF Research Database (Denmark)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse

    2003-01-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers...... exemplify 'soft actuator' technology that may be especially suitable for use in conjunction with human limbs. The electrochemical and mechanical properties of polypyrrole dodecyl benzene sulphonate actuator films have been studied with this application in mind. The results show that the time constants...

  8. Suppression effects on musical and verbal memory.

    Science.gov (United States)

    Schendel, Zachary A; Palmer, Caroline

    2007-06-01

    Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

  9. Feedback-enhanced sensitivity in optomechanics

    DEFF Research Database (Denmark)

    Harris, Glen I.; Andersen, Ulrik L.; Knittel, Joachim

    2012-01-01

    The intracavity power, and hence sensitivity, of optomechanical sensors is commonly limited by parametric instability. Here we characterize the degradation of sensitivity induced by parametric instability in a micron-scale cavity optomechanical system. Feedback via optomechanical transduction...... and electrical gradient force actuation is applied to suppress the parametric instability. As a result a 5.4-fold increase in mechanical motion transduction sensitivity is achieved to a final value of 1.9×10-18 mHz-1/2....

  10. Pressure suppression pool thermal mixing

    International Nuclear Information System (INIS)

    Cook, D.H.

    1984-01-01

    A model is developed and verified to describe the thermal mixing that occurs in the pressure suppression pool (PSP) of a commercial BWR. The model is designed specifically for a Mark-I containment and is intended for use in severe accident sequence analyses. The model produces space and time dependent temperature results throughout the PSP and is useful for evaluating the bulk PSP thermal mixing, the condensation effectiveness of the PSP, and the long-term containment integrity. The model is designed to accommodate single or multiple discharging T-quenchers, a PSP circumferential circulation induced by the residual heat removal system discharge, and the thermal stratification of the pool that occurs immediately after the relief valves close. The PSP thermal mixing model is verified by comparing the model predicted temperatures to experimental temperatures that were measured in an operating BWR suppression pool. The model is then used to investigate several PSP thermal mixing problems that include the time to saturate at full relief valve flow, the temperature response to a typical stuck open relief valve scenario, and the effect of operator rotation of the relief valve discharge point

  11. Physical limits of feedback noise-suppression in biological networks

    International Nuclear Information System (INIS)

    Zhang, Jiajun; Yuan, Zhanjiang; Zhou, Tianshou

    2009-01-01

    Feedback is a ubiquitous control mechanism of biological networks, and has also been identified in a variety of regulatory systems and organisms. It has been shown that, for a given gain and with negligible intrinsic noise, negative feedback impairs noise buffering whereas positive feedback enhances noise buffering. We further investigate the influence of negative and positive feedback on noise in output signals by considering both intrinsic and extrinsic noise as well as operator noise. We find that, while maintaining the system sensitivity, either there exists a minimum of the output noise intensity corresponding to a biologically feasible feedback strength, or the output noise intensity is a monotonic function of feedback strength bounded by both biological and dynamical constraints. In both cases, feedback noise-suppression is physically limited. In other words, noise suppressed by negative or positive feedback cannot be reduced without limitation even in the case of slow transcription

  12. The role of suppression in amblyopia.

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

    2011-06-13

    This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

  13. Molecular mechanisms for sweet-suppressing effect of gymnemic acids.

    Science.gov (United States)

    Sanematsu, Keisuke; Kusakabe, Yuko; Shigemura, Noriatsu; Hirokawa, Takatsugu; Nakamura, Seiji; Imoto, Toshiaki; Ninomiya, Yuzo

    2014-09-12

    Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans but not in mice. This sweet-suppressing effect of gymnemic acids is diminished by rinsing the tongue with γ-cyclodextrin (γ-CD). However, little is known about the molecular mechanisms underlying the sweet-suppressing effect of gymnemic acids and the interaction between gymnemic acids versus sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human (h) sweet receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in transiently transfected HEK293 cells. Similar to previous studies in humans and mice, gymnemic acids (100 μg/ml) inhibited the [Ca(2+)]i responses to sweet compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of gymnemic acids rapidly disappeared after rinsing the HEK293 cells with γ-CD. Using mixed species pairings of human and mouse sweet receptor subunits and chimeras, we determined that the transmembrane domain of hT1R3 was mainly required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis in the transmembrane domain of hT1R3 revealed that the interaction site for gymnemic acids shared the amino acid residues that determined the sensitivity to another sweet antagonist, lactisole. Glucuronic acid, which is the common structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our models, gymnemic acids were predicted to dock to a binding pocket within the transmembrane domain of hT1R3. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    Science.gov (United States)

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

    2014-01-03

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

  16. Transcranial pulsed electromagnetic fields for multiple chemical sensitivity: Study protocol for a randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Skovbjerg, Sine; Arendt-Nielsen, Lars

    2013-01-01

    . The symptoms may have severe impact on patients' lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer...... follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia...

  17. Safety system for pressure suppression

    International Nuclear Information System (INIS)

    Wood, L.E.; Ludwig, G.J.; Tulsa, O.

    1975-01-01

    The rupture disk with rated breaking points is constrained by two supporting elements and has a convex-concave shape. For pressure suppression, it is reversable inversely to its bulging. Its surface has notches which are the rated breaking points and respond to higher pressures. The centre of the rupture disk contains an area of relatively smaller thickness that will burst at lower pressure and thus makes it applicable for lower pressures. For the response of the rupture disk centre, a thrust ring with a central opening may also be used. Its edge is formed into a convex-concave section supported on the edge of the rupture disk on the exit side. The free centre of the rupture disk is then the area of relative weakness. (RW/AK) [de

  18. MEK5 suppresses osteoblastic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kaneshiro, Shoichi [Department of Orthopaedic Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka City, Osaka 553-0003 (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Higuchi, Chikahisa, E-mail: c-higuchi@umin.ac.jp [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  19. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    Energy Technology Data Exchange (ETDEWEB)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.

  20. Charmonium formation and suppression in nuclear matter

    International Nuclear Information System (INIS)

    Xu Jiajun; Wang Jia; Zhuang Chao; Zhuang Pengfei

    2005-01-01

    The coupling Schroedinger equations describing the evolution of cc-bar states in nuclear matter are analytically and systematically solved via perturbation method, and the correlation between charmonium formation and nuclear absorption is investigated. After calculating J/Ψ and Ψ' suppression in nucleon-nucleus collisions and comparing with experiment data, it is found that the formation time effect plays an important rule in charmonium suppression, especially in Ψ' suppression. (authors)

  1. Poppers: more evidence of suppressed immunity.

    Science.gov (United States)

    James, J S

    1999-08-20

    Evidence from studies in mice shows that exposure to isobutyl nitrite suppresses the immune system. This immune suppression allows for bacterial growth in the lungs and livers of infected mice and can inhibit the ability of mediastinal lymph nodes to respond to antigen-specific stimulation. The mechanism for immune suppression may be a reduction in CD4+ and CD8+ T cell populations in the mediastinal lymph nodes following pulmonary infection with Listeria monocytogenes.

  2. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    Directory of Open Access Journals (Sweden)

    Hsin-Hung Li

    2015-10-01

    Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

  3. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    Science.gov (United States)

    Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

    2015-10-01

    In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

  4. Generalized tolerance sensitivity and DEA metric sensitivity

    OpenAIRE

    Neralić, Luka; E. Wendell, Richard

    2015-01-01

    This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  5. Generalized tolerance sensitivity and DEA metric sensitivity

    Directory of Open Access Journals (Sweden)

    Luka Neralić

    2015-03-01

    Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  6. Assessing the efficiency of Wolbachia driven Aedes mosquito suppression by delay differential equations.

    Science.gov (United States)

    Huang, Mugen; Luo, Jiaowan; Hu, Linchao; Zheng, Bo; Yu, Jianshe

    2017-12-14

    To suppress wild population of Aedes mosquitoes, the primary transmission vector of life-threatening diseases such as dengue, malaria, and Zika, an innovative strategy is to release male mosquitoes carrying the bacterium Wolbachia into natural areas to drive female sterility by cytoplasmic incompatibility. We develop a model of delay differential equations, incorporating the strong density restriction in the larval stage, to assess the delicate impact of life table parameters on suppression efficiency. Through mathematical analysis, we find the sufficient and necessary condition for global stability of the complete suppression state. This condition, combined with the experimental data for Aedes albopictus population in Guangzhou, helps us predict a large range of releasing intensities for suppression success. In particular, we find that if the number of released infected males is no less than four times the number of mosquitoes in wild areas, then the mosquito density in the peak season can be reduced by 95%. We introduce an index to quantify the dependence of suppression efficiency on parameters. The invariance of some quantitative properties of the index values under various perturbations of the same parameter justifies the applicability of this index, and the robustness of our modeling approach. The index yields a ranking of the sensitivity of all parameters, among which the adult mortality has the highest sensitivity and is considerably more sensitive than the natural larvae mortality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Nuisance alarm suppression techniques for fibre-optic intrusion detection systems

    Science.gov (United States)

    Mahmoud, Seedahmed S.; Visagathilagar, Yuvaraja; Katsifolis, Jim

    2012-02-01

    The suppression of nuisance alarms without degrading sensitivity in fibre-optic intrusion detection systems is important for maintaining acceptable performance. Signal processing algorithms that maintain the POD and minimize nuisance alarms are crucial for achieving this. A level crossings algorithm is presented for suppressing torrential rain-induced nuisance alarms in a fibre-optic fence-based perimeter intrusion detection system. Results show that rain-induced nuisance alarms can be suppressed for rainfall rates in excess of 100 mm/hr, and intrusion events can be detected simultaneously during rain periods. The use of a level crossing based detection and novel classification algorithm is also presented demonstrating the suppression of nuisance events and discrimination of nuisance and intrusion events in a buried pipeline fibre-optic intrusion detection system. The sensor employed for both types of systems is a distributed bidirectional fibre-optic Mach Zehnder interferometer.

  8. Boiling Suppression in Convective Flow

    International Nuclear Information System (INIS)

    Aounallah, Y.

    2004-01-01

    The development of convective boiling heat transfer correlations and analytical models has almost exclusively been based on measurements of the total heat flux, and therefore on the overall two-phase heat transfer coefficient, when the well-known heat transfer correlations have often assumed additive mechanisms, one for each mode of heat transfer, convection and boiling. While the global performance of such correlations can readily be assessed, the predictive capability of the individual components of the correlation has usually remained elusive. This becomes important when, for example, developing mechanistic models for subcooled void formation based on the partitioning of the wall heat flux into a boiling and a convective component, or when extending a correlation beyond its original range of applications where the preponderance of the heat transfer mechanisms involved can be significantly different. A new examination of existing experimental heat transfer data obtained under fixed hydrodynamic conditions, whereby the local flow conditions are decoupled from the local heat flux, has allowed the unequivocal isolation of the boiling contribution over a broad range of thermodynamic qualities (0 to 0.8) for water at 7 MPa. Boiling suppression, as the quality increases, has consequently been quantified, thus providing valuable new insights on the functionality and contribution of boiling in convective flows. (author)

  9. High blood pressure and visual sensitivity

    Science.gov (United States)

    Eisner, Alvin; Samples, John R.

    2003-09-01

    The study had two main purposes: (1) to determine whether the foveal visual sensitivities of people treated for high blood pressure (vascular hypertension) differ from the sensitivities of people who have not been diagnosed with high blood pressure and (2) to understand how visual adaptation is related to standard measures of systemic cardiovascular function. Two groups of middle-aged subjects-hypertensive and normotensive-were examined with a series of test/background stimulus combinations. All subjects met rigorous inclusion criteria for excellent ocular health. Although the visual sensitivities of the two subject groups overlapped extensively, the age-related rate of sensitivity loss was, for some measures, greater for the hypertensive subjects, possibly because of adaptation differences between the two groups. Overall, the degree of steady-state sensitivity loss resulting from an increase of background illuminance (for 580-nm backgrounds) was slightly less for the hypertensive subjects. Among normotensive subjects, the ability of a bright (3.8-log-td), long-wavelength (640-nm) adapting background to selectively suppress the flicker response of long-wavelength-sensitive (LWS) cones was related inversely to the ratio of mean arterial blood pressure to heart rate. The degree of selective suppression was also related to heart rate alone, and there was evidence that short-term changes of cardiovascular response were important. The results suggest that (1) vascular hypertension, or possibly its treatment, subtly affects visual function even in the absence of eye disease and (2) changes in blood flow affect retinal light-adaptation processes involved in the selective suppression of the flicker response from LWS cones caused by bright, long-wavelength backgrounds.

  10. Half-body x-ray suppresses the acquisition of delayed-type hypersensitivity in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Maguire, Jr, H C

    1979-01-01

    800 R half-body x-ray suppressed the acquisition of allergic contact dermatitis in mice (1) if the x-ray field included the lymph nodes regional to the sensitization site, and (2) when x-ray was given during, but not immediately before, induction of the sensitivity.

  11. Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Warrington, R.J.; Rutherford, W.J.

    1990-01-01

    A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is radiation sensitive, directed against CESS targets and not mediated by inhibition of IL-6 production, and associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus

  12. Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness

    Science.gov (United States)

    Forder, Lewis; Taylor, Olivia; Mankin, Helen; Scott, Ryan B.; Franklin, Anna

    2016-01-01

    The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d’) and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object’s stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain. PMID:27023274

  13. Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness.

    Science.gov (United States)

    Forder, Lewis; Taylor, Olivia; Mankin, Helen; Scott, Ryan B; Franklin, Anna

    2016-01-01

    The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d') and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object's stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain.

  14. Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness.

    Directory of Open Access Journals (Sweden)

    Lewis Forder

    Full Text Available The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry, detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d' and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object's stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain.

  15. The polaroid suppression test in a pediatric population with ophthalmologic disorders.

    Science.gov (United States)

    Pott, Jan Willem R; Kingma, C; Verhoeff, K; Grootendorst, R J; de Faber, J T H N

    2003-04-01

    The Polaroid suppression test (PST) is a new method for early detection of amblyogenic factors by screening for suppression. The apparatus can elicit suppression with the use of Polaroid filters. The aim of the present study was to examine a population of children with known ophthalmologic disorders using the PST to determine the rate of false-negative results of the PST. Six hundred four children, varying in age between 3 and 15 years (mean, 7.9) were examined using the PST. Ophthalmologic disorders ranged from strabismus and amblyopia to refractive disorders. Mean testing time for the PST was 43 seconds. The PST could not be administered to 34 children (5.6%); 443 children (73.3%) had abnormal results; and 127 children (22.2%) showed no suppression. The suppression in constant strabismus was detected in almost all cases. The sensitivity for accommodative forms of strabismus was lower, but amblyopia was never missed in these cases. In children with normal eye alignment, only 2.7% with an interocular acuity difference of more than 0.1 logMAR had no suppression. Of all 119 children with clinical defined amblyopia, only 1 (0.8%) did not have suppression. Overall sensitivity of the PST for strabismus and/or abnormal interocular acuity difference was 96.2% and specificity was 41.1%. The PST has great potential as a visual screening tool in young children. Only few children with amblyogenic factors were missed. Thus, the test can differentiate those children at risk for amblyopia from normally sighted children. Because specificity is lower, all children showing suppression with the PST in a screening situation should have further examination by the health care worker before being referred to the ophthalmologist.

  16. Repetition suppression in ventral visual cortex is diminished as a function of increasing autistic traits

    NARCIS (Netherlands)

    Ewbank, M.P.; Rhodes, G.; von dem Hagen, E.A.H.; Powell, T.E.; Bright, N.; Stoyanova, R.Z.; Baron-Cohen, S.; Calder, A.J.

    2015-01-01

    Repeated viewing of a stimulus causes a change in perceptual sensitivity, known as a visual aftereffect. Similarly, in neuroimaging, repetitions of the same stimulus result in a reduction in the neural response, known as repetition suppression (RS). Previous research shows that aftereffects for

  17. Dim light adaptation attenuates acute melatonin suppression in humans.

    Science.gov (United States)

    Jasser, Samar A; Hanifin, John P; Rollag, Mark D; Brainard, George C

    2006-10-01

    Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p light exposure, varying with the conditions of light adaptation prior to exposure.

  18. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    Science.gov (United States)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  19. Psychopathology and Thought Suppression: A Quantitative Review

    Science.gov (United States)

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  20. Volatile suppressing method for radioactive iodine

    International Nuclear Information System (INIS)

    Ohara, Atsushi; Haruguchi, Keiko.

    1997-01-01

    In the present invention, a metal plate is disposed above the pool water surface of a suppression chamber disposed to a reactor container in order to reduce evaporation of radioactive iodine released from a suppression pool. A metal plate is disposed above the pool water surface of the suppression chamber disposed to the reactor container. In addition, a metal plate is disposed around the space connecting a bent tube extending from a dry well to underwater of suppression pool water and a gas bent tube extending from the suppression chamber to an emergency gas processing system. Spray water is supplied for cooling the suppression chamber d as a means for cooling the metal plate. Then, among iodine released to the suppression chamber, elemental iodine liberated from the pool water is deposited on the surface of the metal plate, and the amount of iodine to be flown into and processed by an emergency gas processing system or a filter bent system can be reduced. (T.M.)

  1. Regional Extent of Peripheral Suppression in Amblyopia.

    Science.gov (United States)

    Babu, Raiju J; Clavagnier, Simon; Bobier, William R; Thompson, Benjamin; Hess, Robert F

    2017-04-01

    Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

  2. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  3. Chondromalacia patellae: fat-suppressed MR imaging.

    Science.gov (United States)

    Rose, P M; Demlow, T A; Szumowski, J; Quinn, S F

    1994-11-01

    To evaluate the accuracy of fat-suppressed magnetic resonance (MR) imaging in diagnosing chondromalacia patellae. Seventy-one patients underwent fat-suppressed MR imaging and arthroscopy of the patellofemoral compartment. Findings were classified as early or advanced chondromalacia or as normal and were correlated with arthroscopic findings. Early and advanced stages of chondromalacia patellae were reliably detected, with positive predictive values of 85% and 92%, respectively. Specificity in early stages was 94% and in late stages was 98%. However, the overall accuracies did not differ substantially from those reported in studies that did not use fat-suppressed imaging. Axial, fat-suppressed MR imaging accurately depicts changes caused by chondromalacia patellae. Early stages can be seen as intrasubstance changes of increased signal intensity. Results of this study suggest a high degree of specificity in excluding both early and advanced changes.

  4. METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

    Science.gov (United States)

    Visek, W.J.

    1963-04-23

    This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

  5. Suppression factors in diffractive photoproduction of dijets

    International Nuclear Information System (INIS)

    Klasen, Michael; Kramer, Gustav

    2010-06-01

    After new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut. (orig.)

  6. Attention modulates sensory suppression during back movements.

    Science.gov (United States)

    Van Hulle, Lore; Juravle, Georgiana; Spence, Charles; Crombez, Geert; Van Damme, Stefaan

    2013-06-01

    Tactile perception is often impaired during movement. The present study investigated whether such sensory suppression also occurs during back movements, and whether this would be modulated by attention. In two tactile detection experiments, participants simultaneously engaged in a movement task, in which they executed a back-bending movement, and a perceptual task, consisting of the detection of subtle tactile stimuli administered to their upper or lower back. The focus of participants' attention was manipulated by raising the probability that one of the back locations would be stimulated. The results revealed that tactile detection was suppressed during the execution of the back movements. Furthermore, the results of Experiment 2 revealed that when the stimulus was always presented to the attended location, tactile suppression was substantially reduced, suggesting that sensory suppression can be modulated by top-down attentional processes. The potential of this paradigm for studying tactile information processing in clinical populations is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Suppression of instability in rotatory hydromagnetic convection

    Indian Academy of Sciences (India)

    first time by Lord Rayleigh [9] for the idealized case of two free boundaries. Rayleigh's theory shows that the gravity-dominated thermal instability in liquid layer ... suppressed for oscillatory perturbations by the simultaneous application of a ...

  8. Combustion suppressing device for leaked sodium

    International Nuclear Information System (INIS)

    Ooto, Akihiro.

    1985-01-01

    Purpose: To suppress the atmospheric temperature to secure the building safety and shorten the recovery time after the leakage in a chamber for containing sodium leaked from coolant circuit equipments or pipeways of LMFBR type rector by suppressing the combustion of sodium contained in the chamber. Constitution: To the inner wall of a chamber for containing sodium handling equipments, are vertically disposed a panel having a coolant supply port at the upper portion and a coolant discharge port at the lower portion thereof and defined with a coolant flowing channel and a panel for sucking the coolant discharged from the abovementioned panel and exhausting the same externally. Further, a corrugated combustion suppressing plate having apertures for draining the condensated leaked sodium is disposed near the sodium handling equipments. If ruptures are resulted to the sodium handling equipments or pipeway, leaked sodium is passed through the drain apertures in the suppressing plate and stored at the bottom of the containing chamber. (Horiuchi, T.)

  9. Dual Role of Interleukin-23 in Epicutaneously-Sensitized Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Katsunori Masaki

    2014-01-01

    Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hy- perresponsiveness.

  10. Suppressing Tsetse Flies to Improve Lives

    International Nuclear Information System (INIS)

    Potterton, Louise; Pavlicek, Petr; Parker, Andrew

    2013-01-01

    In 2009, the government-run Southern Tsetse Eradication Project (STEP) in Ethiopia, with the support of the IAEA, started to carry out intensive activities to suppress the fly population using insecticides. The fly population is now down by 90%. The benefits of tsetse suppression can be seen all over the region. Diary produce is now widely available at markets and healthy animals can be seen everywhere in farming and transport

  11. Gamma camera scatter suppression unit WAM

    International Nuclear Information System (INIS)

    Kishi, Haruo; Shibahara, Noriyuki; Hirose, Yoshiharu; Shimonishi, Yoshihiro; Oumura, Masahiro; Ikeda, Hozumi; Hamada, Kunio; Ochi, Hironobu; Itagane, Hiroshi.

    1990-01-01

    In gamma camera imaging, scattered radiation is one of big factors to decrease image contrast. Simply, scatter suppression makes signal to noise ratio larger, but it makes statistics error because of radionuclide injection limit to the human body. EWA is a new method that suppresses scattered radiation and improves image contrast. In this article, WAM which is commercialized EWA method by Siemens Gammasonics Inc. is presented. (author)

  12. Ibrutinib suppresses alloantibody responses in a mouse model of allosensitization.

    Science.gov (United States)

    Kim, Irene; Wu, Gordon; Chai, Ning-Ning; Klein, Andrew S; Jordan, Stanley

    2017-12-01

    Ibrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia. We recently carried out studies to determine if ibrutinib could modify alloantibody responses. A mouse model of allogenic sensitization using a C57BL/6 mouse as the recipient of a skin allograft from an HLA-A2 transgenic mouse was utilized to examine the effects of ibrutinib on alloantibody responses and B cell effector functions. Donor-specific antibody (DSA) levels were measured in a flow-cytometric antibody binding assay. Splenic T and B cell subsets and plasma cells were analyzed in flow cytometry. Control mice developed peak levels of DSA IgM at day 14 PTx while the ibrutinib treated mice had significantly lower levels of DSA IgM (p=0.0047). Control mice developed HLA.A2-specific IgG antibodies at day 14 (230±60 MFI) and reached peak levels at day 21 (426±61 MFI). In contrast, mice in the treatment group had low levels of HLA.A2-specific IgG at day 14 (109±59 MFI, p=0.004) and day 21 (241±86 MFI, p=0.003). FACS analysis found a reduction of B220 + or CD19 + B cell population (pibrutinib attenuated recall DSA IgG responses to re-sensitization (pIbrutinib is effective in suppressing alloantibody responses through blocking BTK-mediated BCR signaling, leading to reduction of B cells and short-lived plasma cells in the spleens. Use of ibrutinib may provide benefits to HLA-sensitized transplant patients for alloantibody suppression. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    Science.gov (United States)

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  14. Local Turbulence Suppression and Shear Flow Dynamics During qmin-Triggered Internal Transport Barriers on DIII-D

    Science.gov (United States)

    Shafer, M. W.; McKee, G. R.; Schlossberg, D. J.; Austin, M. E.; Burrell, K. H.

    2008-11-01

    Long-wavelength turbulence (kρiITBs) may form. Application of off-axis ECH slows the q-profile evolution and increases ρqmin, both of which enhance turbulence measurements using a new high-sensitivity large-area (8x,8) 2D BES array. The measured transient turbulence suppression is localized to the low-order rational surface (qmin= 2, 5/2, 3, etc.). Measured poloidal flow shear transiently exceeds the turbulence decorrelation rate, which is consistent with shear suppression. The localized suppression zone propagates radially outward, nearly coincident with the low-order surface.

  15. GNOSIS: THE FIRST INSTRUMENT TO USE FIBER BRAGG GRATINGS FOR OH SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Trinh, Christopher Q.; Ellis, Simon C.; Bland-Hawthorn, Joss; Bryant, Julia; O' Byrne, John [Sydney Institute for Astronomy, School of Physics, The University of Sydney, NSW 2006 (Australia); Lawrence, Jon S.; Horton, Anthony J.; Shortridge, Keith; Case, Scott; Colless, Matthew; Gers, Luke; Lee, Steve; Miziarski, Stan [Australian Astronomical Observatory, 105 Delhi Road, North Ryde, P.O. Box 915, NSW 1670 (Australia); Leon-Saval, Sergio G. [Institute of Photonics and Optical Science, School of Physics, University of Sydney, NSW 2006 (Australia); Couch, Warrick; Glazebrook, Karl [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, P.O. Box 218, Hawthorn, VIC 3122 (Australia); Freeman, Kenneth [Research School of Astronomy and Astrophysics, Australian National University, Weston Creek, ACT 2611 (Australia); Loehmannsroeben, Hans-Gerd [innoFSPEC-Institut fuer Chemie/Physikalische Chemie, Universitaet Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm (Germany); Haynes, Roger; Roth, Martin M., E-mail: c.trinh@physics.usyd.edu.au [innoFSPEC-Leibniz-Institut fuer Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); and others

    2013-02-01

    The near-infrared is an important part of the spectrum in astronomy, especially in cosmology because the light from objects in the early universe is redshifted to these wavelengths. However, deep near-infrared observations are extremely difficult to make from ground-based telescopes due to the bright background from the atmosphere. Nearly all of this background comes from the bright and narrow emission lines of atmospheric hydroxyl (OH) molecules. The atmospheric background cannot be easily removed from data because the brightness fluctuates unpredictably on short timescales. The sensitivity of ground-based optical astronomy far exceeds that of near-infrared astronomy because of this long-standing problem. GNOSIS is a prototype astrophotonic instrument that utilizes 'OH suppression fibers' consisting of fiber Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47 and 1.7 {mu}m. GNOSIS was commissioned at the 3.9 m Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibers, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput ( Almost-Equal-To 60%) and excellent suppression of the skylines by the OH suppression fibers, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS+IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise dominated. OH suppression fibers could potentially impact ground-based astronomy at the level of adaptive optics or

  16. GNOSIS: THE FIRST INSTRUMENT TO USE FIBER BRAGG GRATINGS FOR OH SUPPRESSION

    International Nuclear Information System (INIS)

    Trinh, Christopher Q.; Ellis, Simon C.; Bland-Hawthorn, Joss; Bryant, Julia; O'Byrne, John; Lawrence, Jon S.; Horton, Anthony J.; Shortridge, Keith; Case, Scott; Colless, Matthew; Gers, Luke; Lee, Steve; Miziarski, Stan; Leon-Saval, Sergio G.; Couch, Warrick; Glazebrook, Karl; Freeman, Kenneth; Löhmannsröben, Hans-Gerd; Haynes, Roger; Roth, Martin M.

    2013-01-01

    The near-infrared is an important part of the spectrum in astronomy, especially in cosmology because the light from objects in the early universe is redshifted to these wavelengths. However, deep near-infrared observations are extremely difficult to make from ground-based telescopes due to the bright background from the atmosphere. Nearly all of this background comes from the bright and narrow emission lines of atmospheric hydroxyl (OH) molecules. The atmospheric background cannot be easily removed from data because the brightness fluctuates unpredictably on short timescales. The sensitivity of ground-based optical astronomy far exceeds that of near-infrared astronomy because of this long-standing problem. GNOSIS is a prototype astrophotonic instrument that utilizes 'OH suppression fibers' consisting of fiber Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47 and 1.7 μm. GNOSIS was commissioned at the 3.9 m Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibers, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput (≈60%) and excellent suppression of the skylines by the OH suppression fibers, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS+IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise dominated. OH suppression fibers could potentially impact ground-based astronomy at the level of adaptive optics or greater. However, until a

  17. Long-term tinnitus suppression with linear octave frequency transposition hearing AIDS.

    Directory of Open Access Journals (Sweden)

    Elisabeth Peltier

    Full Text Available Over the last three years of hearing aid dispensing, it was observed that among 74 subjects fitted with a linear octave frequency transposition (LOFT hearing aid, 60 reported partial or complete tinnitus suppression during day and night, an effect still lasting after several months or years of daily use. We report in more details on 38 subjects from whom we obtained quantified measures of tinnitus suppression through visual analog scaling and several additional psychoacoustic and audiometric measures. The long-term suppression seems independent of subject age, and of duration and subjective localization of tinnitus. A small but significant correlation was found with audiogram losses but not with high frequency loss slope. Long-term tinnitus suppression was observed for different etiologies, but with a low success rate for sudden deafness. It should be noted that a majority of subjects (23 had a history of noise exposure. Tinnitus suppression started after a few days of LOFT hearing aid use and reached a maximum after a few weeks of daily use. For nine subjects different amounts of frequency shifting were tried and found more or less successful for long-term tinnitus suppression, no correlation was found with tinnitus pitch. When the use of the LOFT hearing aid was stopped tinnitus reappeared within a day, and after re-using the LOFT aid it disappeared again within a day. For about one third of the 38 subjects a classical amplification or a non linear frequency compression aid was also tried, and no such tinnitus suppression was observed. Besides improvements in audiometric sensitivity to high frequencies and in speech discrimination scores, LOFT can be considered as a remarkable opportunity to suppress tinnitus over a long time scale. From a pathophysiological viewpoint these observations seem to fit with a possible re-attribution of activity to previously deprived cerebral areas corresponding to high frequency coding.

  18. A compact clinical instrument for quantifying suppression.

    Science.gov (United States)

    Black, Joanne M; Thompson, Benjamin; Maehara, Goro; Hess, Robert F

    2011-02-01

    We describe a compact and convenient clinical apparatus for the measurement of suppression based on a previously reported laboratory-based approach. In addition, we report and validate a novel, rapid psychophysical method for measuring suppression using this apparatus, which makes the technique more applicable to clinical practice. By using a Z800 dual pro head-mounted display driven by a MAC laptop, we provide dichoptic stimulation. Global motion stimuli composed of arrays of moving dots are presented to each eye. One set of dots move in a coherent direction (termed signal) whereas another set of dots move in a random direction (termed noise). To quantify performance, we measure the signal/noise ratio corresponding to a direction-discrimination threshold. Suppression is quantified by assessing the extent to which it matters which eye sees the signal and which eye sees the noise. A space-saving, head-mounted display using current video technology offers an ideal solution for clinical practice. In addition, our optimized psychophysical method provided results that were in agreement with those produced using the original technique. We made measures of suppression on a group of nine adult amblyopic participants using this apparatus with both the original and new psychophysical paradigms. All participants had measurable suppression ranging from mild to severe. The two different psychophysical methods gave a strong correlation for the strength of suppression (rho = -0.83, p = 0.006). Combining the new apparatus and new psychophysical method creates a convenient and rapid technique for parametric measurement of interocular suppression. In addition, this apparatus constitutes the ideal platform for suppressors to combine information between their eyes in a similar way to binocularly normal people. This provides a convenient way for clinicians to implement the newly proposed binocular treatment of amblyopia that is based on antisuppression training.

  19. Acrolein exposure suppresses antigen-induced pulmonary inflammation

    Science.gov (United States)

    2013-01-01

    Background Adverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity. Results Exposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein

  20. Ipsilateral distortion product otoacoustic emission (2 f1-f2) suppression in children with sensorineural hearing loss

    Science.gov (United States)

    Abdala, Carolina; Fitzgerald, Tracy S.

    2003-08-01

    Distortion product otoacoustic emission (DPOAE) ipsilateral suppression has been applied to study cochlear function and maturation in laboratory animals and humans. Although DPOAE suppression appears to be sensitive to regions of specialized cochlear function and to cochlear immaturity, it is not known whether it reflects permanent cochlear damage, i.e., sensorineural hearing loss (SNHL), in a reliable and systematic manner in humans. Eight school-aged children with mild-moderate SNHL and 20 normal-hearing children served as subjects in this study. DPOAE (2 f1-f2) suppression data were collected at four f2 frequencies (1500, 3000, 4000, and 6000 Hz) using moderate-level primary tones. Features of the DPOAE iso-suppression tuning curves and suppression growth were analyzed for both subject groups. Results show that DPOAE suppression tuning curves from hearing-impaired subjects can be reliably recorded. DPOAE suppression tuning curves were generally normal in appearance and shape for six out of eight hearing-impaired subjects but showed subtle abnormalities in at least one feature. There was not one single trend or pattern of abnormality that characterized all hearing-impaired subjects. The most prominent patterns of abnormality included: broadened tuning, elevated tip, and downward shift of tip frequency. The unique patterns of atypical DPOAE suppression in subjects with similar audiograms may suggest different patterns of underlying sensory cell damage. This speculation warrants further investigation.

  1. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  2. Interocular suppression in children with deprivation amblyopia.

    Science.gov (United States)

    Hamm, Lisa; Chen, Zidong; Li, Jinrong; Black, Joanna; Dai, Shuan; Yuan, Junpeng; Yu, Minbin; Thompson, Benjamin

    2017-04-01

    In patients with anisometropic or strabismic amblyopia, interocular suppression can be minimized by presenting high contrast stimulus elements to the amblyopic eye and lower contrast elements to the fellow eye. This suggests a structurally intact binocular visual system that is functionally suppressed. We investigated whether suppression can also be overcome by contrast balancing in children with deprivation amblyopia due to childhood cataracts. To quantify interocular contrast balance, contrast interference thresholds were measured using an established dichoptic global motion technique for 21 children with deprivation amblyopia, 14 with anisometropic or mixed strabismic/anisometropic amblyopia and 10 visually normal children (mean age mean=9.9years, range 5-16years). We found that interocular suppression could be overcome by contrast balancing in most children with deprivation amblyopia, at least intermittently, and all children with anisometropic or mixed anisometropic/strabismic amblyopia. However, children with deprivation amblyopia due to early unilateral or bilateral cataracts could tolerate only very low contrast levels to the stronger eye indicating strong suppression. Our results suggest that treatment options reliant on contrast balanced dichoptic presentation could be attempted in a subset of children with deprivation amblyopia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Suppression of new particle formation from monoterpene oxidation by NOx

    Science.gov (United States)

    Wildt, J.; Mentel, T. F.; Kiendler-Scharr, A.; Hoffmann, T.; Andres, S.; Ehn, M.; Kleist, E.; Müsgen, P.; Rohrer, F.; Rudich, Y.; Springer, M.; Tillmann, R.; Wahner, A.

    2014-03-01

    The impact of nitrogen oxides (NOx = NO + NO2) on new particle formation (NPF) and on photochemical ozone production from real plant volatile organic compound (BVOC) emissions was studied in a laboratory setup. At high NOx conditions ([BVOC] / [NOx] 23 ppb) new particle formation was suppressed. Instead, photochemical ozone formation was observed resulting in higher hydroxyl radical (OH) and lower nitrogen monoxide (NO) concentrations. When [NO] was reduced back to levels below 1 ppb by OH reactions, NPF was observed. Adding high amounts of NOx caused NPF to be slowed by orders of magnitude compared to analogous experiments at low NOx conditions ([NOx] ~300 ppt), although OH concentrations were higher. Varying NO2 photolysis enabled showing that NO was responsible for suppression of NPF. This suggests that peroxy radicals are involved in NPF. The rates of NPF and photochemical ozone production were related by power law dependence with an exponent approaching -2. This exponent indicated that the overall peroxy radical concentration must have been similar when NPF occurred. Thus, permutation reactions of first-generation peroxy radicals cannot be the rate limiting step in NPF from monoterpene oxidation. It was concluded that permutation reactions of higher generation peroxy-radical-like intermediates limit the rate of new particle formation. In contrast to the strong effects on the particle numbers, the formation of particle mass was substantially less sensitive to NOx concentrations. If at all, yields were reduced by about an order of magnitude only at very high NOx concentrations.

  4. Testosterone suppression of CRH-stimulated cortisol in men.

    Science.gov (United States)

    Rubinow, David R; Roca, Catherine A; Schmidt, Peter J; Danaceau, Merry A; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-10-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (pcortisol area under the curve was lower at a trend level (pcortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (pcortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

  5. Population characteristics and the suppression of nonnative Burbot

    Science.gov (United States)

    Klein, Zachary B.; Quist, Michael C.; Rhea, Darren T.; Senecal, Anna C.

    2016-01-01

    Burbot Lota lota were illegally introduced into the Green River, Wyoming, drainage and have since proliferated throughout the system. Burbot in the Green River pose a threat to native species and to socially, economically, and ecologically important recreational fisheries. Therefore, managers of the Green River are interested in implementing a suppression program for Burbot. We collected demographic data on Burbot in the Green River (summer and autumn 2013) and used the information to construct an age-based population model (female-based Leslie matrix) to simulate the population-level response of Burbot to the selective removal of different age-classes. Burbot in the Green River grew faster, matured at relatively young ages, and were highly fecund compared with other Burbot populations within the species’ native distribution. The age-structured population model, in conjunction with demographic information, indicated that the Burbot population in the Green River could be expected to increase under current conditions. The model also indicated that the Burbot population in the Green River would decline once total annual mortality reached 58%. The population growth of Burbot in the Green River was most sensitive to age-0 and age-1 mortality. The age-structured population model indicated that an increase in mortality, particularly for younger age-classes, would result in the effective suppression of the Burbot population in the Green River.

  6. Suppression of adoptive antituberculosis immunity by normal recipient animals

    International Nuclear Information System (INIS)

    Lefford, M.J.

    1983-01-01

    Adoptive immunity is poorly expressed in normal syngeneic mice. This phenomenon was studied by using experimental antituberculosis immunity as a model system representing pure cell-mediated immunity. Expression of adoptive immunity was facilitated by pretreating recipients with sublethal ionizing radiation (500 rads) or high doses (200 mg/kg) of cyclophosphamide or by using adult thymectomized, lethally irradiated, bone-marrow-reconstituted (TXB) mice. Adult thymectomy was less effective, and a low dose of cyclophosphamide (20 mg/kg) was completely ineffective. The beneficial effect of sublethal irradiation was reduced over time; it persisted for 4 weeks and was absent after 8 weeks. Attempts to restore the suppressed state of normal mice to sublethally irradiated mice by using normal spleen or thymus cells did not succeed. Even in rats, which express adoptive antituberculosis immunity without immunosuppressive treatment, the use of sublethally irradiated or TXB recipients potentiated adoptive immunity. It was concluded that suppression of adoptive immunization in normal recipient mice is mediated predominantly, if not exclusively, by T lymphocytes that are sensitive to a number of immunosuppressive agents. The suppressor cells are long-lived and can be regenerated from precursors that are resistant to 500 but not to 900 rads of ionizing radiation

  7. Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Hai-Bo Xing

    2018-01-01

    Full Text Available Pancreatic adenocarcinoma has an exceedingly poor prognosis, accounting for five-year survival of less than 5%. Presently, improving the efficacy of pancreatic adenocarcinoma treatment has been the focus of medical researchers worldwide. Recently, it has been suggested that deregulation of interleukin- (IL- 6 is caused by a key gene involved in the beginning and development of pancreatic adenocarcinoma. Herein, we investigated whether suppression of IL-6 could augment gemcitabine sensitivity in the PANC-1 cells. We found considerably higher expression of IL-6 in pancreatic adenocarcinoma tissues than that in the adjacent nontumorous tissues. Suppression of IL-6 by shRNA resulted in apoptosis as well as inhibition of cell proliferation and tumorigenicity. In addition, suppression of IL-6 remarkably promoted antitumor effect of gemcitabine, indicating that the combination of shRNA targeting IL-6 with gemcitabine may provide a potential clinical approach for pancreatic cancer therapy.

  8. Effects of thought suppression on episodic memory.

    Science.gov (United States)

    Rassin, E; Merckelbach, H; Muris, P

    1997-11-01

    Subjects were shown a short film fragment. Following this, one group of subjects (n = 26) was instructed to suppress their thoughts about the film, while the other group (n = 24) received no instructions. After 5 hrs subjects returned to the laboratory and completed a questionnaire testing their memory about the film. Results showed that suppression subjects reported a higher frequency of thoughts about the film than control subjects. No evidence was obtained for Wegner, Quillian, and Houston's (1996; Journal of Personality and Social Psychology, 71, 680-691) claim that suppression has an undermining effect on memory for chronology. Possible causes for the differences between the results as obtained by Wegner et al., and those found in the present study are discussed. These causes may pertain to the experimental design, but also to differences in emotional impact of the stimulus material that was used in both studies.

  9. Wing rock suppression using forebody vortex control

    Science.gov (United States)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  10. Quantum-mechanical suppression of bremsstrahlung

    Energy Technology Data Exchange (ETDEWEB)

    Becker-Szendy, R.; Keller, L.; Niemi, G.; Perl, M.; Rochester, L. [Stanford Univ., CA (United States); Anthony, P. [Stanford Univ., CA (United States)]|[Lawrence Livermore National Lab., CA (United States); Bosted, P. [American Univ., Washington, DC (United States); Cavalli-Sforza, M.; Kelley, L.; Klein, S. [Univ. of California, Santa Cruz, CA (United States)] [and others

    1994-12-01

    The authors have studied quantum-mechanical suppression of bremsstrahlung of low-energy 1-500 MeV photons from high-energy 25 GeV electrons. They have measured the LPM effect, where multiple scattering of the radiating electron destroys coherence required for the emission of low-energy photons, and the dielectric effect, where the emitted photon traveling in the radiator medium interferes with itself. For the experiment, the collaboration developed a novel method of extracting a parasitic low-intensity high-energy electron beam into the fixed target area during normal SLC operation of the accelerator. The results agree quantitatively with Migdal`s calculation of the LPM effect. Surface effects, for which there is no satisfactory theoretical prediction, are visible at low photon energies. For very thin targets, the suppression disappears, as expected. Preliminary results on dielectric suppression of bremsstrahlung are in qualitative agreement with the expectation.

  11. Shielding design of ITER pressure suppression system

    International Nuclear Information System (INIS)

    Yamauchi, Michinori; Sato, Satoshi; Nishitani, Takeo; Kawasaki, Hiromitsu

    2006-01-01

    The duct shield from streaming D-T neutrons has been designed for the ITER pressure suppression system. Streaming calculations are performed with the DUCT-III code for the region from the inlet of the pressure relief line to the rupture disk. Next, the neutron permeation through the shield is studied by Monte Carlo calculations with the MCNP code. It is found that 0.15 m thick iron shield is enough to suppress the permeating component from the outside. In addition, it is suggested that the volume of the shield can be reduced by about 30% if the optimized iron shield structure having localized thickness across intense permeation paths is employed to shield the pressure suppression line. (T.I.)

  12. Suppression of Spiral Wave in Modified Orengonator Model

    International Nuclear Information System (INIS)

    Ma Jun; Wang Chunni; Jin Wuyin; Yi Ming

    2008-01-01

    In this paper, a spatial perturbation scheme is proposed to suppress the spiral wave in the modified Orengonator model, which is used to describe the chemical reaction in the light-sensitive media. The controllable external illumination Φ is perturbed with a spatial linear function. In our numerical simulation, the scheme is investigated by imposing the external controllable illumination on the space continuously and/or intermittently. The numerical simulation results confirm that the stable rotating spiral wave still can be removed with the scheme proposed in this paper even if the controllable Φ changed vs. time and space synchronously. Then the scheme is also used to control the spiral wave and turbulence in the modified Fitzhugh-Nagumo model. It is found that the scheme is effective to remove the sable rotating and meandering spiral wave but it costs long transient period and intensity of the gradient parameter to eliminate the spiral turbulence

  13. Ultraviolet light-induced suppression of antigen presentation

    International Nuclear Information System (INIS)

    Spellman, C.W.; Tomasi, T.B.

    1983-01-01

    Ultraviolet (UV) light irradiation of animals results in the development of specific T suppressor cells that inhibit antitumor immune responses. It is thought that suppression may arise as a consequence of altered antigen presentation by UV-irradiated epidermal cells. This hypothesis is based on evidence demonstrating that specific lymphoid tissues from UV-irradiated hosts exhibit impaired antigen-presenting function and that animals cannot be contact sensitized when antigens are applied to a UV-irradiated skin site. Langerhans cells of the skin are likely candidates as targets of UV-induced defects in antigen presentation as they bear Fc and C3b receptors, express Ia antigens, are of bone marrow origin, and are capable of presenting antigen in vitro. We speculate on the possible clinical usefulness of UV-induced tolerance to specific antigens such as those encountered in monoclonal antibody therapy and tissue transplantation

  14. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  15. Suppression of charmonium production in hadron gas

    International Nuclear Information System (INIS)

    Faustov, R.N.; Vasilevskaya, I.G.

    1991-01-01

    The problem of J/ψ charmonium production suppression under heavy ion collisions is investigated. The processes of charmonium disintegration in hadron gas are considered: π+J/ψ → π+c+c-bar and ρ+J/ψ → D+D. Based on the results obtained one can assume that charmonium disintegration contribution to J/ψ production suppression under collisions with gas hadrons and the contribution conditioned by the production of quark-gluon plasma, appear to be the effects of similar order of magnitude

  16. Jet suppression measurement with the ATLAS detector

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00443411; The ATLAS collaboration

    2016-01-01

    A hot medium with a high density of unscreened color charges is produced in relativistic heavy ion collisions. Jets are produced at the early stages of this collision and are known to become attenuated as they propagate through the hot matter. One manifestation of this energy loss is a lower yield of jets emerging from the medium than expected in the absence of medium effects. Another manifestation of the energy loss is the modification of the dijet balance and the modification of fragmentation functions. In these proceedings, the latest ATLAS results on single jet suppression, dijet suppression, and modification of the jet internal structure in \\PbPb~collisions are presented.

  17. Star formation suppression in compact group galaxies

    DEFF Research Database (Denmark)

    Alatalo, K.; Appleton, P. N.; Lisenfeld, U.

    2015-01-01

    , bars, rings, tidal tails, and possibly nuclear outflows, though the molecular gas morphologies are more consistent with spirals and earlytype galaxies than mergers and interacting systems. Our CO-imaged HCG galaxies, when plotted on the Kennicutt-Schmidt relation, shows star formation (SF) suppression...... color space. This supports the idea that at least some galaxies in HCGs are transitioning objects, where a disruption of the existing molecular gas in the system suppresses SF by inhibiting the molecular gas from collapsing and forming stars efficiently. These observations, combined with recent work...

  18. Human occipital cortices differentially exert saccadic suppression: intracranial recording in children

    Science.gov (United States)

    Uematsu, Mitsugu; Matsuzaki, Naoyuki; Brown, Erik C.; Kojima, Katsuaki; Asano, Eishi

    2013-01-01

    By repeating saccades unconsciously, humans explore the surrounding world every day. Saccades inevitably move external visual images across the retina at high velocity; nonetheless, healthy humans don’t perceive transient blurring of the visual scene during saccades. This perceptual stability is referred to as saccadic suppression. Functional suppression is believed to take place transiently in the visual systems, but it remains unknown how commonly or differentially the human occipital lobe activities are suppressed at the large-scale cortical network level. We determined the spatial-temporal dynamics of intracranially-recorded gamma activity at 80–150 Hz around spontaneous saccades under no-task conditions during wakefulness and those in darkness during REM sleep. Regardless of wakefulness or REM sleep, a small degree of attenuation of gamma activity was noted in the occipital regions during saccades, most extensively in the polar and least in the medial portions. Longer saccades were associated with more intense gamma-attenuation. Gamma-attenuation was subsequently followed by gamma-augmentation most extensively involving the medial and least involving the polar occipital region. Such gamma-augmentation was more intense during wakefulness and temporally locked to the offset of saccades. The polarities of initial peaks of perisaccadic event-related potentials (ERPs) were frequently positive in the medial and negative in the polar occipital regions. The present study, for the first time, provided the electrophysiological evidence that human occipital cortices differentially exert peri-saccadic modulation. Transiently suppressed sensitivity of the primary visual cortex in the polar region may be an important neural basis for saccadic suppression. Presence of occipital gamma-attenuation even during REM sleep suggests that saccadic suppression might be exerted even without external visual inputs. The primary visual cortex in the medial region, compared to the

  19. Chemical kinetic functional sensitivity analysis: Elementary sensitivities

    International Nuclear Information System (INIS)

    Demiralp, M.; Rabitz, H.

    1981-01-01

    Sensitivity analysis is considered for kinetics problems defined in the space--time domain. This extends an earlier temporal Green's function method to handle calculations of elementary functional sensitivities deltau/sub i//deltaα/sub j/ where u/sub i/ is the ith species concentration and α/sub j/ is the jth system parameter. The system parameters include rate constants, diffusion coefficients, initial conditions, boundary conditions, or any other well-defined variables in the kinetic equations. These parameters are generally considered to be functions of position and/or time. Derivation of the governing equations for the sensitivities and the Green's funciton are presented. The physical interpretation of the Green's function and sensitivities is given along with a discussion of the relation of this work to earlier research

  20. Chemical sensitivity: pathophysiology or pathopsychology?

    Science.gov (United States)

    Genuis, Stephen J

    2013-05-01

    Escalating numbers of people throughout the world are presenting to primary care physicians, allergists, and immunologists with myriad clinical symptoms after low-level exposure to assorted everyday chemicals such as smoke, perfumes, air fresheners, paints, glues, and other products. This clinical state is referred to by various diagnostic labels, including multiple chemical sensitivity disorder, environmental intolerance, chemical sensitivity (CS), and sensitivity-related illness, and has been the subject of much controversy within the health care community. The goal of this study was to provide a brief overview of the etiology, pathogenesis, clinical presentation, and management of CS. An evaluation of the medical community's response to this emerging diagnosis was also explored. This review was prepared by assessing available medical and scientific literature from MEDLINE, as well as by reviewing numerous books, toxicology journals, conference proceedings, government publications, and environmental health periodicals. A primary observation, however, is that there is limited scientific literature available on the issue of CS. The format of a traditional integrated review was chosen because such reviews play a pivotal role in scientific research and professional practice in medical issues with limited primary study and uncharted clinical territory. The sensitization state of CS seems to be initiated by a significant toxic exposure, occurring as a 1-time event, or on surpassing a threshold of toxicity after toxicant accrual from repeated lower-level exposures. Once sensitized through a toxicant-induced loss of tolerance, individuals exposed to inciting triggers such as minute amounts of diverse everyday chemicals may experience various clinical and immune sequelae, sometimes involving lymphocyte, antibody, or cytokine responses. Precautionary avoidance of inciting triggers will prevent symptoms, and desensitization immunotherapy or immune suppression may improve

  1. Assessing fear following retrieval+extinction through suppression of baseline reward seeking vs. freezing

    Directory of Open Access Journals (Sweden)

    Jason eShumake

    2015-12-01

    Full Text Available Freezing has become the predominant measure used in rodent studies of conditioned fear, but conditioned suppression of reward-seeking behavior may provide a measure that is more relevant to human anxiety disorders; that is, a measure of how fear interferes with the enjoyment of pleasurable activities. Previous work has found that an isolated presentation of a fear conditioned stimulus prior to extinction training (retrieval + extinction results in a more robust and longer-lasting reduction in fear. The objective of this study was to assess whether the retrieval + extinction effect is evident using conditioned suppression of reward seeking, operationalized as a reduction in baseline licking (without prior water deprivation for a 10% sucrose solution. We found that, compared to freezing, conditioned suppression of reward seeking was much more sensitive to fear conditioning and far less responsive to extinction training. As in previous work, we found that retrieval + extinction reduced post-extinction fear reinstatement when measured as freezing, but it did not reduce fear reinstatement when measured as conditioned suppression. This suggests that there is still residual fear following retrieval + extinction, or that this procedure only modifies memory traces in neural circuits relevant to the expression of freezing, but not to the suppression of reward seeking.

  2. Suppression of plasma turbulence during optimised shear configurations in JET

    International Nuclear Information System (INIS)

    Conway, G.D.; Borba, D.N.; Alper, B.

    1999-08-01

    Density turbulence suppression is observed in the internal transport barrier (ITB) region of JET discharges with optimised magnetic shear. The suppression occurs in two stages. First, low frequency turbulence is reduced across the plasma core by a toroidal velocity shear generated by intense auxiliary heating. Then when the ITB forms, high frequency turbulence is reduced locally within the steep pressure gradient region of the ITB, consistent with the effects of enhanced E x B poloidal shear. The turbulence suppression is correlated with reduced plasma transport and improved fusion performance. Much effort has been spent in recent years in developing alternative scenarios for operating tokamak fusion reactors. One particular scenario involves reversing or reducing the central magnetic shear to form an internal transport barrier (ITB). The result is reduced plasma core energy transport and enhanced fusion performance. It is believed that ITBs may be formed through a combination of E x B velocity shear and magnetic shear stabilisation of plasma turbulence and instabilities. In this Letter we present results from JET optimised shear discharges showing that turbulence suppression during ITB formation occurs in two stages. First low frequency turbulence is reduced across the plasma core, coinciding with a region of strong toroidal velocity shear; then high frequency turbulence is locally suppressed around the ITB region, consistent with enhanced pressure gradient driven E x B poloidal shear. The measurements were made using a system of X-mode reflectometers consisting of two, dual-channel toroidal correlation reflectometers at 75 GHz (covering plasma outboard edge) and 105 GHz (core and inboard edge), and a 92-96 GHz swept frequency radial correlation reflectometer (plasma core). Reflectometry is a powerful tool for measuring density fluctuations. The highly localised reflection of the microwave beam gives excellent spatial localisation. Measurements can be made

  3. Review of high-sensitivity Radon studies

    Science.gov (United States)

    Wojcik, M.; Zuzel, G.; Simgen, H.

    2017-10-01

    A challenge in many present cutting-edge particle physics experiments is the stringent requirements in terms of radioactive background. In peculiar, the prevention of Radon, a radioactive noble gas, which occurs from ambient air and it is also released by emanation from the omnipresent progenitor Radium. In this paper we review various high-sensitivity Radon detection techniques and approaches, applied in the experiments looking for rare nuclear processes happening at low energies. They allow to identify, quantitatively measure and finally suppress the numerous sources of Radon in the detectors’ components and plants.

  4. Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys.

    Science.gov (United States)

    Hallum, Luke E; Shooner, Christopher; Kumbhani, Romesh D; Kelly, Jenna G; García-Marín, Virginia; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2017-08-23

    In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys ( Macaca nemestrina ) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys ( Macaca nemestrina ) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is

  5. Suppression Situations in Multiple Linear Regression

    Science.gov (United States)

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  6. Cortisol suppresses radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.

    1985-01-01

    It is reported that 10 -7 M cortisol has a significant suppressive effect on radiation-induced transformation in vitro in C3H10T 1/2 cells. Previously reported data showed a significant enhancing effect for similar experiments performed with cortisone. Thus, these two structurally similar glucocorticoid hormones have opposite effects on transformation induced by ionizing radiation. (author)

  7. Cooling device for reactor suppression pool

    International Nuclear Information System (INIS)

    Togasaki, Susumu; Kato, Kiyoshi.

    1994-01-01

    In a cooling device of a reactor suppression pool, when a temperature of pool water is abnormally increased and a heat absorbing portion is heated by, for example, occurrence of an accident, coolants are sent to the outside of the reactor container to actuates a thermally operating portion by the heat energy of coolants and drive heat exchanging fluids of a secondary cooling system. If the heat exchanging fluids are sent to a cooling portion, the coolants are cooled and returned to the heat absorbing portion of the suppression pool water. If the heat absorbing portion is heat pipes, the coolants are evaporated by heat absorbed from the suppression pool water, steams are sent to the thermally operating portion, then coolants are liquefied and caused to return to the heat absorbing portion. If the thermal operation portion is a gas turbine, the gas turbine is operated by the coolants, and it is converted to a rotational force to drive heat exchanging fluids by pumps. By constituting the cooling portion with a condensator, the coolants are condensed and liquefied and returned to the heat absorbing portion of the suppression pool water. (N.H.)

  8. Efflux inhibitor suppresses Streptococcus mutans virulence properties.

    Science.gov (United States)

    Zeng, Huihui; Liu, Jia; Ling, Junqi

    2017-04-01

    It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Suppressive competition: how sounds may cheat sight.

    Science.gov (United States)

    Kayser, Christoph; Remedios, Ryan

    2012-02-23

    In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Measuring colour rivalry suppression in amblyopia.

    Science.gov (United States)

    Hofeldt, T S; Hofeldt, A J

    1999-11-01

    To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes. To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed. In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1. 8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (beta=1.21, psuppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.

  11. Pressure suppression facility for reactor container

    International Nuclear Information System (INIS)

    Fujii, Tadashi; Fukui, Toru; Kataoka, Yoshiyuki; Tominaga, Kenji.

    1993-01-01

    In a nuclear reactor comprising heat transfer surfaces from a pressure suppression pool at the inside to the outer circumferential pool at the outside, a means for supplying water from a water supply source at the outside of the container to the pools is disposed. Then, a heat transfer means is disposed between the pressure suppression chamber and the water cooling pool. The water supply means comprises a pressurization means for applying pressure to water of the water supply source and a water supply channel. Water is supplied into the pressure suppression pool and the outer circumferential pool to elevate the water level and extend the region of heat contact with the water cooling heat transfer means. In addition, since dynamic pressure is applied to the feedwater, for example, by pressurizing the water surface of the water supply source, water can be supplied without using dynamic equipments such as pumps. Then, since water-cooling heat transfer surface can be extended after occurrence of accident, enlargement of a reactor container and worsening of earthquake proofness can be avoided as much as possible, to improve function for suppressing the pressure in the container. Further, since water-cooling heat transfer region can be extended, the arrangement of the water source and the place to which water is supplied is made optional without considering the relative height therebetween, to improve earthquake proofness. (N.H.)

  12. Quarkonium suppression: Gluonic dissociation vs. colour screening

    Indian Academy of Sciences (India)

    mechanism comes into play for the initial conditions taken from the self screened parton cascade model in these studies. Keywords. Quark gluon plasma; J ψ; suppression; dissociation; colour screening. PACS No. 12.38.M. 1. Introduction. The last two decades have seen hectic activity towards identifying unique signatures ...

  13. Aralia elata (Miquel) Seemann Suppresses Inflammatory ...

    African Journals Online (AJOL)

    ISSN: 1596-5996 (print); 1596-9827 (electronic) ... The LPS-induced increase in the production of nitric oxide was concentration- dependently suppressed ... Aralia elata ethanol extract (AEE) exhibits protective ... temperature for 72 h and filtered. The filtered .... scavenging activity in a dose-dependent manner showing a ...

  14. Jet suppression and the flavor dependence of partonic energy loss with ATLAS

    Energy Technology Data Exchange (ETDEWEB)

    Kosek, Tomas

    2016-12-15

    In relativistic heavy ion collisions, a hot medium with a high density of unscreened color charges is produced. One manifestation of the energy loss of jets propagating through the medium is a lower yield of jets and hadrons emerging from this medium than expected in the absence of medium effects. Therefore modifications of the jet yield are directly sensitive to the energy loss mechanism. Furthermore, jets with different flavor content are expected to be affected by the medium in different ways. In this publication, the latest ATLAS results on single hadron suppression along with the complementary measurements of single jet suppression are presented. Rapidity dependence, which is sensitive to the relative energy loss between quark and gluon jets, is discussed. Finally, a new measurement of jet fragmentation functions is presented.

  15. Dithiafulvene-based organic sensitizers using pyridine as the acceptor for dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jun; Cao, Yaxiong; Liang, Xiaozhong; Zheng, Jingxia; Zhang, Fang [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Wei, Shuxian; Lu, Xiaoqing [College of Science, China University of Petroleum, Qingdao, Shandong 266555 (China); Guo, Kunpeng, E-mail: guokunpeng@tyut.edu.cn [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Yang, Shihe, E-mail: chsyang@ust.hk [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China)

    2017-05-01

    Three dithiafulvene-based metal-free organic sensitizers all using pyridine as the acceptor but with different π-bridges of phenyl (DTF-Py1), thienyl (DTF-Py2) and phenyl-thienyl (DTF-Py3) have been designed, synthesized and used as photosensitizers for dye-sensitized solar cells (DSCs). Introducing thienyl unit into the π-bridge, as well as extension of the π-bridge can dramatically improve their light harvesting ability and suppress the electron recombination, thus uplifting the performance of DSCs. The overall power conversion efficiency of DSC based on DTF-Py3 shows the highest efficiency of 2.61% with a short-circuit photocurrent density of 7.99 mA cm{sup -2}, an open-circuit photovoltage of 630 mV, and a fill factor of 0.52, under standard global AM 1.5 solar light condition. More importantly, the long-term stability of the DTF-Py3 based DSCs under 500 h light-soaking has been demonstrated. - Highlights: • Dithiafulvene sensitizers using pyridine ring as the acceptor were synthesized for the first time. • The power conversion efficiency of 2.61% was obtained for DTF-Py3 sensitized cell. • DTF-Py3 loaded TiO{sub 2} film shows improved light harvesting ability and suppressed electron recombination.

  16. Suppressing my memories by listening to yours: The effect of socially triggered context-based prediction error on memory.

    Science.gov (United States)

    Vlasceanu, Madalina; Drach, Rae; Coman, Alin

    2018-05-03

    The mind is a prediction machine. In most situations, it has expectations as to what might happen. But when predictions are invalidated by experience (i.e., prediction errors), the memories that generate these predictions are suppressed. Here, we explore the effect of prediction error on listeners' memories following social interaction. We find that listening to a speaker recounting experiences similar to one's own triggers prediction errors on the part of the listener that lead to the suppression of her memories. This effect, we show, is sensitive to a perspective-taking manipulation, such that individuals who are instructed to take the perspective of the speaker experience memory suppression, whereas individuals who undergo a low-perspective-taking manipulation fail to show a mnemonic suppression effect. We discuss the relevance of these findings for our understanding of the bidirectional influences between cognition and social contexts, as well as for the real-world situations that involve memory-based predictions.

  17. Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise; suggested cut-off points.

    Science.gov (United States)

    Riga, M; Komis, A; Maragkoudakis, P; Korres, G; Danielides, V

    2016-12-01

    Normative otoacoustic emission (OAE) suppression values are currently lacking and the role of cochlear efferent innervation in tinnitus is controversial. The aim of this study was to investigate the association between tinnitus and medial olivocochlear bundle (MOCB) malfunction. Potential suppression amplitude cut-off criteria that could differentiate participants with tinnitus from those without were sought. Mean suppression amplitudes of transient evoked OAEs and distortion product OAEs by contralateral white noise (50 dBSL) were recorded. Six mean suppression amplitudes criteria were validated as possible cut-off points. The population consisted of normal hearing (n = 78) or presbycusic adults (n = 19) with tinnitus or without (n = 28 and 13, respectively) chronic tinnitus (in total, n = 138 78 females/60males, aged 49 ± 14 years). Participants with mean suppression values lower than 0.5-1 dBSPL seem to present a high probability to report tinnitus (specificity 88-97%). On the other hand, participants with mean suppression values larger than 2-2.5dBSPL seem to present a high probability of the absence of tinnitus (sensitivity 87-99%). Correlations were stronger among participants with bilateral presence or absence of tinnitus. This study seem to confirm an association between tinnitus and low suppression amplitudes (<1 dBSPL), which might evolve into an objective examination tool, supplementary to conventional audiological testing.

  18. Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

    Science.gov (United States)

    Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

    2015-01-01

    Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

  19. Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

    Science.gov (United States)

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

    2011-01-01

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

  20. Sensitivity study of micro four-point probe measurements on small samples

    DEFF Research Database (Denmark)

    Wang, Fei; Petersen, Dirch Hjorth; Hansen, Torben Mikael

    2010-01-01

    probes than near the outer ones. The sensitive area is defined for infinite film, circular, square, and rectangular test pads, and convergent sensitivities are observed for small samples. The simulations show that the Hall sheet resistance RH in micro Hall measurements with position error suppression...

  1. Benchmark enclosure fire suppression experiments - phase 1 test report.

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  2. [The advances of suppression in research of amblyopia].

    Science.gov (United States)

    Liu, S; Liu, H

    2016-04-11

    Suppression that is the result of interocular competition is an important machanism of amblyopia. The imbalance of suppression may lead the consequence to amblyopia. In the early study, researchers had raised the theory of II. Quadratic Summation which had revealed the relationship of interocular interaction and suppression. In some basic researches, other studies had showed the most possible anatomic location of suppression. Recently, researchers found a new method to quantify the interocular suppression named the noise model. Further studies found a novel disinhibition therapy to treat amblyopia. We summarized the research advances in suppression and disinhibition treatment in amblyopia. (Chin J Ophthalmol, 2016, 52: 305-308).

  3. EUROGAM: A high efficiency escape suppressed spectrometer array

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, P J [Liverpool Univ. (United Kingdom). Oliver Lodge Lab.

    1992-08-01

    EUROGAM is a UK-France collaboration to develop and build a high efficiency escape suppressed spectrometer array. The project has involved the development of both germanium (Ge) and bismuth germanate (BGO) detectors to produce crystals which are both bigger and have a more complex geometry. As a major investment for the future, the collaboration has developed a new electronics and data acquisition system based on the VXI and VME standards. The array will start its experimental programme in mid 1992 at the Nuclear Structure Facility at Daresbury, U.K. At this stage it will have a total photopeak efficiency (for 1.33 MeV gamma-rays) of {approx} 4.5%. This will give an improvement in sensitivity (relative to presently operating arrays) of a factor of about 10. When EUROGAM moves to France in mid 1993 its photopeak efficiency will have increased to about 8.5% which will result in an increase in sensitivity of a further factor of about 10. In this article I will concentrate on the array which will operate at Daresbury in 1992 and only briefly cover the developments which will take place for the full array before it is used in France in 1993. (author). 13 refs., 2 tabs., 10 figs.

  4. EUROGAM: A high efficiency escape suppressed spectrometer array

    International Nuclear Information System (INIS)

    Nolan, P.J.

    1992-01-01

    EUROGAM is a UK-France collaboration to develop and build a high efficiency escape suppressed spectrometer array. The project has involved the development of both germanium (Ge) and bismuth germanate (BGO) detectors to produce crystals which are both bigger and have a more complex geometry. As a major investment for the future, the collaboration has developed a new electronics and data acquisition system based on the VXI and VME standards. The array will start its experimental programme in mid 1992 at the Nuclear Structure Facility at Daresbury, U.K. At this stage it will have a total photopeak efficiency (for 1.33 MeV gamma-rays) of ∼ 4.5%. This will give an improvement in sensitivity (relative to presently operating arrays) of a factor of about 10. When EUROGAM moves to France in mid 1993 its photopeak efficiency will have increased to about 8.5% which will result in an increase in sensitivity of a further factor of about 10. In this article I will concentrate on the array which will operate at Daresbury in 1992 and only briefly cover the developments which will take place for the full array before it is used in France in 1993. (author). 13 refs., 2 tabs., 10 figs

  5. Acidic conditions induce the suppression of CD86 and CD54 expression in THP-1 cells.

    Science.gov (United States)

    Mitachi, Takafumi; Mezaki, Minori; Yamashita, Kunihiko; Itagaki, Hiroshi

    2018-01-01

    To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54. We measured expression levels after THP-1 cells were exposed to representative contact allergens, i.e., 2,4-dinitrochlorobenzene and imidazolidinyl urea, under acidic conditions. These conditions were set by exposure to hydrochloric acid, lactic acid, and citric acid. An acidic extracellular pH (6-7) suppressed the augmentation of CD86 and CD54 levels by the sensitizer. Additionally, when the CD86/CD54 expression levels were suppressed, a reduction in the intracellular pH was confirmed. Furthermore, we observed that Na + /H + exchanger 1 (NHE-1), a protein that contributes to the regulation of extracellular/intracellular pH, is involved in CD86 and CD54 expression. These findings suggest that the extracellular/intracellular pH has substantial effects on in vitro skin sensitization markers and should be considered in evaluations of the safety of mixtures and commercial products in the future.

  6. Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

    Science.gov (United States)

    Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

    2016-06-28

    We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

  7. Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

    OpenAIRE

    Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

    2016-01-01

    We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play...

  8. Tumor Suppression and Sensitization to Taxol Induced Apoptosis of E1A In Breast Cancer Cells

    National Research Council Canada - National Science Library

    Liao, Yong

    2004-01-01

    .... Because a phase I E1A gene therapy protocol for human breast and ovarian cancers was completed and a phase II clinical trial is undergoing, we also plan to develop an alternative E1A mutant construct...

  9. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Mouritsen, Annette; Mogensen, Signe Sloth

    2010-01-01

    Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis.......Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis....

  10. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Mouritsen, Annette; Mogensen, Signe Sloth

    2010-01-01

    Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis....

  11. Tumor Suppression and Sensitization to Taxol Induced Apoptosis of E1A in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Liao, Yong

    2002-01-01

    The purpose of this project is to study the molecular mechanisms underlying ElA's proapoptotic effect and anti-tumor activity and to dissect the functional domains of ElA that are critical for its antitumor activity...

  12. Tumor Suppression and Sensitization to Taxol Induces Apoptosis of EIA in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Liao, Yong

    2005-01-01

    The purpose of this project is to study the molecular mechanisms underlying ElA's proapoptotic effect and anti-tumor activity and to dissect the functional domains of ElA that are critical for its antitumor activity...

  13. Context Sensitive Modeling of Cancer Drug Sensitivity.

    Directory of Open Access Journals (Sweden)

    Bo-Juen Chen

    Full Text Available Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression, an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features.

  14. Overcoming fixation with repeated memory suppression.

    Science.gov (United States)

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  15. Magnetic fusion development for global warming suppression

    International Nuclear Information System (INIS)

    Li Jiangang; Zhang Jie; Duan Xuru

    2010-01-01

    Energy shortage and environmental pollution are two critical issues for human beings in the 21st century. There is an urgent need for new sustainable energy to meet the fast growing demand for clean energy. Fusion is one of the few options which may be able to satisfy the requirement for large scale sustainable energy generation and global warming suppression and therefore must be developed as quickly as possible. Fusion research has been carried out for the past 50 years. It is too long to wait for another 50 years to generate electricity by fusion. A much more aggressive approach should be taken with international collaboration towards the early use of fusion energy to meet the urgent needs for energy and global warming suppression.

  16. Suppression of Rabi oscillations for moving atoms

    International Nuclear Information System (INIS)

    Navarro, B.; Egusquiza, I. L.; Muga, J. G.; Hegerfeldt, G. C.

    2003-01-01

    The well-known laser-induced Rabi oscillations of a two-level atom are shown to be suppressed under certain conditions when the atom is entering a laser-illuminated region. For temporal Rabi oscillations the effect has two regimes: a first classical-like one, taking place at intermediate atomic velocities, and a second purely quantum case at low velocities. The classical regime is associated with the formation of incoherent internal states of the atom in the laser region, whereas in the quantum, low velocity regime the laser projects the atom onto a pure internal state that can be controlled by detuning. Spatial Rabi oscillations are only suppressed in this low velocity, quantum regime

  17. Sleep deprivation suppresses aggression in Drosophila

    Science.gov (United States)

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  18. Suppression of Poxvirus Replication by Resveratrol.

    Science.gov (United States)

    Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

    2017-01-01

    Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  19. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

    Full Text Available Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV, the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  20. Managing for soil health can suppress pests

    Directory of Open Access Journals (Sweden)

    Amanda Hodson

    2016-08-01

    Full Text Available A “healthy” soil can be thought of as one that functions well, both agronomically and ecologically, and one in which soil biodiversity and crop management work in synergy to suppress pests and diseases. UC researchers have pioneered many ways of managing soil biology for pest management, including strategies such as soil solarization, steam treatment and anaerobic soil disinfestation, as well as improvements on traditional methods, such as reducing tillage, amending soil with organic materials, and cover cropping. As managing for soil health becomes more of an explicit focus due to restrictions on the use of soil fumigants, integrated soil health tests will be needed that are validated for use in California. Other research needs include breeding crops for disease resistance and pest suppressive microbial communities as well as knowledge of how beneficial organisms influence plant health.

  1. Prevention and suppression of metal packing fires.

    Science.gov (United States)

    Roberts, Mark; Rogers, William J; Sam Mannan, M; Ostrowski, Scott W

    2003-11-14

    Structured packing has been widely used because of large surface area that makes possible columns with high capacity and efficiency. The large surface area also contributes to fire hazards because of hydrocarbon deposits that can easily combust and promote combustion of the thin metal packing materials. Materials of high surface area that can fuel fires include reactive metals, such as titanium, and materials that are not considered combustible, such as stainless steel. Column design and material selection for packing construction is discussed together with employee training and practices for safe column maintenance and operations. Presented also are methods and agents for suppression of metal fires. Guidance for prevention and suppression of metal fires is related to incidents involving packing fires in columns.

  2. Compton suppression through rise-time analysis

    International Nuclear Information System (INIS)

    Selvi, S.; Celiktas, C.

    2007-01-01

    We studied Compton suppression for 60 Co and 137 Cs radioisotopes using a signal selection criterion based on contrasting the fall time of the signals composing the photo peak with those composing the Compton continuum. The fall time criterion is employed by using the pulse shape analysis observing the change in the fall times of the gamma-ray pulses. This change is determined by measuring the changes in the rise times related to the fall time of the scintillator and the timing signals related to the fall time of the input signals. We showed that Compton continuum suppression is achieved best via the precise timing adjustment of an analog rise-time analyzer connected to a NaI(Tl) scintillation spectrometer

  3. Abnormal Grain Growth Suppression in Aluminum Alloys

    Science.gov (United States)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  4. Pressure suppression device for a reactor container

    International Nuclear Information System (INIS)

    Shimizu, Toshiaki

    1982-01-01

    Purpose: To prevent damages in drain pipes or the likes upon the water level increase due to blowing of incompressible gases. Constitution: An exhaust pipe for guiding escaping steams is connected to a main steam releaf valve. The exhaust pipe is guided into pressure-suppression-chamber water through the inside of a dry-well and by way of a vent pipe, a vent header and a drain pipe or a downcomer. Since the exhaust pipe is not exposed to the water surface inside the pressure suppression chamber, even if steams blow out into the dry-well by the rapture of pipeways or the likes to rapidly increase the water level, the water surface does not hit on the exhaust pipe, whereby the damages for the exhaust pipe and support members can be prevented to improve the reliability. (Seki, T.)

  5. Myc suppression of Nfkb2 accelerates lymphomagenesis

    International Nuclear Information System (INIS)

    Keller, Ulrich; Huber, Jürgen; Nilsson, Jonas A; Fallahi, Mohammad; Hall, Mark A; Peschel, Christian; Cleveland, John L

    2010-01-01

    Deregulated c-Myc expression is a hallmark of several human cancers where it promotes proliferation and an aggressive tumour phenotype. Myc overexpression is associated with reduced activity of Rel/NF-κB, transcription factors that control the immune response, cell survival, and transformation, and that are frequently altered in cancer. The Rel/NF-κB family member NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-κB2 augments lymphocyte proliferation. Precancerous Eμ-Myc-transgenic B cells, Eμ-Myc lymphomas and human Burkitt lymphoma samples were assessed for Nfkb2 expression. The contribution of Nfkb2 to Myc-driven apoptosis, proliferation, and lymphomagenesis was tested genetically in vivo. Here we report that the Myc oncoprotein suppresses Nfkb2 expression in vitro in primary mouse fibroblasts and B cells, and in vivo in the Eμ-Myc transgenic mouse model of human Burkitt lymphoma (BL). NFKB2 suppression by Myc was also confirmed in primary human BL. Promoter-reporter assays indicate that Myc-mediated suppression of Nfkb2 occurs at the level of transcription. The contribution of Nfkb2 to Myc-driven lymphomagenesis was tested in vivo, where Nfkb2 loss was shown to accelerate lymphoma development in Eμ-Myc transgenic mice, by impairing Myc's apoptotic response. Nfkb2 is suppressed by c-Myc and harnesses Myc-driven lymphomagenesis. These data thus link Myc-driven lymphomagenesis to the non-canonical NF-κB pathway

  6. Hangar Fire Suppression Utilizing Novec 1230

    Science.gov (United States)

    2018-01-01

    fuel fires in aircraft hangars. A 30×30×8-ft concrete-and-steel test structure was constructed for this test series. Four discharge assemblies...that agent concentration in the test structure exceeded the required extinguishing concentration for at least 5 min after discharge. Two fire ...involved suppression of a 4.6-gal, approximately 5-ft diameter, Jet-A pool fire . Both fires were successfully extinguished by the Novec 1230 discharge

  7. Thought Suppression in Patients With Bipolar Disorder

    OpenAIRE

    Miklowitz, David J.; Alatiq, Yousra; Geddes, John R.; Goodwin, Guy M.; Williams, J. Mark G.

    2010-01-01

    Suppression of negative thoughts has been observed under experimental conditions among patients with major depressive disorder (MDD) but has never been examined among patients with bipolar disorder (BD). Patients with BD (n = 36), patients with MDD (n = 20), and healthy controls (n = 20) completed a task that required unscrambling 6-word strings into 5-word sentences, leaving out 1 word. The extra word allowed the sentences to be completed in a negative, neutral, or ?hyperpositive? (manic/goa...

  8. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  9. Suppression of radiation excitation in focusing environment

    International Nuclear Information System (INIS)

    Huang, Z.; Ruth, R.D.

    1996-12-01

    Radiation damping and quantum excitation in an electron damping ring and a straight focusing channel are reviewed. They are found to be the two limiting cases in the study of a general bending and focusing combined system. In the intermediate regime where the radiation formation length is comparable to the betatron wavelength, quantum excitation can be exponentially suppressed by focusing field. This new regime may have interesting applications in the generation of ultra-low emittance beams

  10. Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

    Directory of Open Access Journals (Sweden)

    Sutmuller Roger PM

    2011-03-01

    Full Text Available Abstract Background Regulatory T cells (Treg play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2 agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff cells and dendritic cells (DCs individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.

  11. Structure sensitivity in adsorption

    DEFF Research Database (Denmark)

    Hammer, Bjørk; Nielsen, Ole Holm; Nørskov, Jens Kehlet

    1997-01-01

    The structure sensitivity of CO adsorption on different flat, stepped, kinked and reconstructed Pt surfaces is studied using large-scale density-functional calculations. We find an extremely strong structure sensitivity in the adsorption energy with variations up to 1 eV (or 100%) from one...... structure to the next. We propose a model to explain this behavior, and use it to discuss more generally the origin of structure sensitivity in heterogeneous catalysis....

  12. Suppressing bullfrog larvae with carbon dioxide

    Science.gov (United States)

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  13. Variation in plant defense suppresses herbivore performance

    Science.gov (United States)

    Pearse, Ian; Paul, Ryan; Ode, Paul J.

    2018-01-01

    Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

  14. Abscopal suppression of bone marrow erythropoiesis

    International Nuclear Information System (INIS)

    Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

    1978-01-01

    Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

  15. Adaptive Filtering for Aeroservoelastic Response Suppression, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — CSA Engineering proposes the design of an adaptive aeroelastic mode suppression for advanced fly-by-wire aircraft, which will partition the modal suppression...

  16. The Suppression of Internal Unrest in South West Africa (Namibia ...

    African Journals Online (AJOL)

    AM Fokkens

    suppression of the Bondelswarts and the actions against Chief Ipumbu. This article .... firepower was an appropriate response to suppress the uprising of local ..... Morris accompanied by Beukes and a commando of 50 men, moved east.

  17. How sensitizing is chlorocresol?

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hamann, K

    1984-01-01

    Chlorocresol is a biocide with widespread use in industry and pharmaceutical products. It is an occasional human contact sensitizer. The sensitizing potential of chlorocresol was judged strong using the guinea pig maximization test (GPMT) and doubtful in the less sensitive open epicutaneous test......% in pet. showed 11 reactions among 1462 patients tested, but none were explainable and reproducible during re-tests and provocative use tests, indicating that the GPMT overestimated the sensitization potential. The results from guinea pig allergy tests cannot stand alone but have to be validated by other...

  18. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  19. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Science.gov (United States)

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  20. Suppressive therapy for radiation-associated nodular thyroid disease

    International Nuclear Information System (INIS)

    Tamura, Kazuo; Shimaoka, Katsutaro; Tsukada, Yoshiaki; Razack, M.S.; Sciasicia, Michael.

    1981-01-01

    A thyroid screening program for individuals who had irradiation to the head and neck areas was started at Roswell Park Memorial Institute in February 1977 and by June 1979, 1,071 patients were seen in the clinic. Three hundred and ninety-six patients were found to have palpable abnormalities of the thyroid, and following pretreatment evaluation, suppressive therapy with triiodothyronine (T3) (50 μg/day) or DT (desiccated thyroid) (120 mg/day) was administered in a double-blind fashion. Two hundred fifty patients with nodular disease completed 6 mo of treatment and are analyzed in this paper. Pretreatment thyroid function tests showed that two patients had hypothyroidism with a high thyroid-stimulating hormone (TSH) and a low thyroxine level. A high incidence of thyroid autoantibodies was also noted and surgical findings confirmed a high incidence of chronic thyroiditis. Complete disappearance of the nodules was seen in 29% of the patients, and in addition, 38% of the patients were seen to have significant shrinkage of the nodules, indicating that radiation-associated thyroid nodules were as sensitive to the thyroactive agents as nonirradiated nodular thyroid disease. There was little difference in the response rate between T3 and DT. Both agents suppressed circulating TSH levels to an unmeasurable level in 76% of the patients. There was no correlation between scan findings and response rates. Thyroid carcinoma was found in 19% of the patients who underwent surgery; although all were well-differentiated carcinomas, two-thirds of the patients already had evidence of dissemination and/or invasion suggesting the aggressive nature of postirradiation thyroid carcinoma. (author)

  1. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    Science.gov (United States)

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  2. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

    Science.gov (United States)

    Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

    2015-02-12

    We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

  3. Exploring Genetic Suppression Interactions on a Global Scale

    OpenAIRE

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire

    2016-01-01

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...

  4. Hepatic Flavin-Containing Monooxygenase 3 Enzyme Suppressed by Type 1 Allergy-Produced Nitric Oxide.

    Science.gov (United States)

    Tanino, Tadatoshi; Bando, Toru; Komada, Akira; Nojiri, Yukie; Okada, Yuna; Ueda, Yukari; Sakurai, Eiichi

    2017-11-01

    Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450 oxidative enzymes. T helper 2 cell-activated allergic diseases produce excess levels of nitric oxide (NO) that modify the functions of proteins. However, it remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs metabolized by FMOs. This study investigated alterations of hepatic microsomal FMO1 and FMO3 activities in type 1 allergic mice and further examined the interaction of FMO1 and FMO3 with allergy-induced NO. Imipramine (IMP; FMO1 substrate) N- oxidation activity was not altered in allergic mice with high serum NO and immunoglobulin E levels. At 7 days after primary sensitization (PS7) or secondary sensitization (SS7), benzydamine (BDZ; FMO1 and FMO3 substrate) N- oxygenation was significantly decreased to 70% of individual controls. The expression levels of FMO1 and FMO3 proteins were not significantly changed in the sensitized mice. Hepatic inducible NO synthase (iNOS) mRNA level increased 5-fold and 15-fold in PS7 and SS7 mice, respectively, and hepatic tumor necrosis factor- α levels were greatly enhanced. When a selective iNOS inhibitor was injected into allergic mice, serum NO levels and BDZ N- oxygenation activity returned to control levels. NO directly suppressed BDZ N- oxygenation, which was probably related to FMO3-dependent metabolism in comparison with IMP N- oxidation. In hepatic microsomes from PS7 and SS7 mice, the suppression of BDZ N- oxygenation was restored by ascorbate. Therefore, type 1 allergic mice had differentially suppressed FMO3-dependent BDZ N- oxygenation. The suppression of FMO3 metabolism related to reversible S- nitrosyl modifications of iNOS-derived NO. NO is expected to alter FMO3-metabolic capacity-limited drug pharmacokinetics in humans. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Compost made of organic wastes suppresses fusariosis

    Science.gov (United States)

    Kuryntseva, Polina; Galitskaya, Polina; Biktasheva, Liliya; Selivanovkaya, Svetlana

    2017-04-01

    Fungal plant diseases cause dramatic yield losses worldwide. Usually, pesticides are used for soil sanitation, and it results in practically pest-free soils, although pesticides cause a biological vacuum, which present many horticultural disadvantages. Suppressive composts, which possess both fertilizing properties for plants and inhibiting properties for plant pathogens, represent an effective and environmentally friendly alternative to conventional pesticides. In this study, composts obtained from agricultural organic wastes were applied to suppress Fusarium oxysporum of tomato plants in model experiments. Composts were made of mixtures of the widespread organic wastes sampled in Tatarstan (Russia): straw (SW), corn wastes (CW), chicken manure (ChM), cattle manure (CM) and swine manure (SM). 11 two- and three-component mixtures were prepared to obtain the optimal carbon-nitrogen, moisture and pH balances, and composted for 210 days. It was found that the thermophilic phase of composting in all the mixtures lasted from 2 to 35 days, and was characterized by significant fluctuations in temperature, i.e. from 27°C to 59°C. In the initial mixtures, the dissolved organic carbon (DOC) content was between 10 and 62 mg kg-1; it fell significantly on day 13, and then continuously decreased up to day 102, and subsequently remained low. For all the mixtures, maximal respiration activity was observed in the beginning of composting (231.9 mg CO2-C g-1 day-1). After 23 days, this parameter decreased significantly, and fluctuations subsided. The phytotoxicity of the initial compost mixtures varied from 18% (SW+SM) to 100% (CW+ChM+SM, CW+ChM); however, the trends in the dynamics were similar. After 120 days of composting, 5 of 11 samples were not phytotoxic. After 120 days of composting, each mixture was divided into two parts; one was inoculated with a biopreparation consisting of four microbial strains (Trichoderma asperellum, Pseudomonas putida, Pseudomonas fluorescens and

  6. One-tone suppression in the frog auditory nerve

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    Sixty-seven fibers of a sample of 401 in the auditory nerve of grassfrogs (Rana temporaria) showed one-tone suppression, i.e., their spontaneous activity was suppressed by tones. All fibers were afferents from the amphibian papilla with best frequencies between 100 and 400 Hz. Best suppression...

  7. Venture capital: States suffer as suppression expenses climb

    Science.gov (United States)

    Krista Gebert

    2008-01-01

    The high cost of suppressing wildfires is taking a toll on federal and state agencies alike. Large wildland fires are complex, costly events influenced by a vast array of physical, climatic, and social factors. During five of the last eight years, the Forest Services' wildfire suppression expenditures have topped $1 billion, and total federal wildland suppression...

  8. Microbial enrichment to enhance the disease suppressive activity of compost

    NARCIS (Netherlands)

    Postma, J.; Montenari, M.; Boogert, van den P.H.J.F.

    2003-01-01

    Compost amended soil has been found to be suppressive against plant diseases in various cropping systems. The level and reproducibility of disease suppressive properties of compost might be increased by the addition of antagonists. In the present study, the establishment and suppressive activity of

  9. Tuned cavity magnetometer sensitivity.

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  10. Cobalt sensitization and dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P

    2012-01-01

    : This clinical review article presents clinical and scientific data on cobalt sensitization and dermatitis. It is concluded that cobalt despite being a strong sensitizer and a prevalent contact allergen to come up on patch testing should be regarded as a very complex metal to test with. Exposure...

  11. Multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron

    2013-01-01

    BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

  12. Assessing Sensitiveness to Transport

    DEFF Research Database (Denmark)

    Lieb, Christoph; Suter, Stefan; Sánchez, Alfredo

    Summary The EU-project ASSET (ASessing SEnsitiveness to Transport) aims at developing and implementing a concise concept to assess transport sensitive areas (TSA) in a European context, i.e. areas in which transport leads to more serious impacts than in other areas. The aim of work package 2 (WP2...

  13. Finnish Teachers’ Ethical Sensitivity

    Directory of Open Access Journals (Sweden)

    Elina Kuusisto

    2012-01-01

    Full Text Available The study examined the ethical sensitivity of Finnish teachers (=864 using a 28-item Ethical Sensitivity Scale Questionnaire (ESSQ. The psychometric qualities of this instrument were analyzed, as were the differences in self-reported ethical sensitivity between practicing and student teachers and teachers of different subjects. The results showed that the psychometric qualities of the ESSQ were satisfactory and enabled the use of an explorative factor analysis. All Finnish teachers rated their level of ethical sensitivity as high, which indicates that they had internalized the ethical professionalism of teaching. However, practicing teachers’ assessments were higher than student teachers’. Moreover, science as a subject was associated with lower self-ratings of ethical sensitivity.

  14. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  15. Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

    Directory of Open Access Journals (Sweden)

    Szczygieł Dorota

    2015-09-01

    Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

  16. Suppressed Alpha Oscillations Predict Intelligibility of Speech and its Acoustic Details

    Science.gov (United States)

    Weisz, Nathan

    2012-01-01

    Modulations of human alpha oscillations (8–13 Hz) accompany many cognitive processes, but their functional role in auditory perception has proven elusive: Do oscillatory dynamics of alpha reflect acoustic details of the speech signal and are they indicative of comprehension success? Acoustically presented words were degraded in acoustic envelope and spectrum in an orthogonal design, and electroencephalogram responses in the frequency domain were analyzed in 24 participants, who rated word comprehensibility after each trial. First, the alpha power suppression during and after a degraded word depended monotonically on spectral and, to a lesser extent, envelope detail. The magnitude of this alpha suppression exhibited an additional and independent influence on later comprehension ratings. Second, source localization of alpha suppression yielded superior parietal, prefrontal, as well as anterior temporal brain areas. Third, multivariate classification of the time–frequency pattern across participants showed that patterns of late posterior alpha power allowed best for above-chance classification of word intelligibility. Results suggest that both magnitude and topography of late alpha suppression in response to single words can indicate a listener's sensitivity to acoustic features and the ability to comprehend speech under adverse listening conditions. PMID:22100354

  17. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

    International Nuclear Information System (INIS)

    Klein, T.; Pross, S.; Newton, C.; Friedman, H.

    1986-01-01

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by 3 H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects

  18. Value of fat suppression and dynamic contrast-enhanced MRI in the diagnosis of insulinoma

    International Nuclear Information System (INIS)

    Xu Zengbin; Ruan Lingxiang; Peng Zhiyi; Zhang Minming; Xu Shunliang; Zhang Xidao

    2003-01-01

    Objective: To evaluate the value of fat suppression and dynamic contrast-enhanced MRI in the preoperative localization of insulinoma. Methods: Twelve cases with pathologically proven insulinoma were evaluated with MRI. SE T 1 WI, FSE T 2 WI, T 1 WI and T 2 WI with fat suppression, dynamic contrast-enhanced FMPSPGR sequences were used in MR scanning. Results: On SE T 1 WI, the lesions displayed hypointense in 4, isointense in 8 cases. Lesions showed hyperintense in 4, isointense in 8 cases on FSE T 2 WI. In contrast, 7 cases appeared as hypointense on T 1 WI with fat suppression and 6 cases appeared as hyperintense on T 2 WI with fat suppression. With dynamic contrast-enhanced FMPSPGR sequence 11 of 12 insulinomas were detected. In the arterial phase, the lesions presented as hyperintense with different degrees in 11 cases and isointense in 1 case. 6 cases remained hyperintense and 6 cases were isointense in pancreatic parenchymal and portal phase. 4 lesions were identified only in dynamic enhancement images. The diagnostic accuracy of insulinoma by dynamic contrast-enhanced MRI was 91.7% (11/12) as compared with histological study. Conclusion: The results indicate that dynamic contrast-enhanced MRI is an sensitive and accurate method for the preoperative localization of insulinoma

  19. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  20. Psychophysical research progress of interocular suppression in amblyopic visual system

    Directory of Open Access Journals (Sweden)

    Jing-Jing Li

    2016-03-01

    Full Text Available Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement and modulation of suppression, and new dichoptic treatment intervention that directly target suppression.

  1. Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

    Science.gov (United States)

    Nurul, Islam Mohammed; Mizuguchi, Hiroyuki; Shahriar, Masum; Venkatesh, Pichairajan; Maeyama, Kazutaka; Mukherjee, Pulok K; Hattori, Masashi; Choudhuri, Mohamed Sahabuddin Kabir; Takeda, Noriaki; Fukui, Hiroyuki

    2011-11-01

    Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Bone-suppressed radiography using machine learning

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  3. Bone-suppressed radiography using machine learning

    International Nuclear Information System (INIS)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung

    2016-01-01

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  4. Prospective comparison of 3D FIESTA versus fat-suppressed 3D SPGR MRI in evaluating knee cartilage lesions

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.; Yu, C. [Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Wu, H. [Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)], E-mail: lilyboston2002@163.com; Daniel, K. [Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Hu, D.; Xia, L.; Pan, C.; Xu, A.; Hu, J.; Wang, L.; Peng, W. [Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Li, F. [Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

    2009-10-15

    Aim: To prospectively compare the accuracy of three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) sequences with that of fat-suppressed three-dimensional spoiled gradient-recalled (3D SPGR) in the diagnosis of knee articular cartilage lesions, using arthroscopy as the reference standard. Materials and methods: Fifty-eight knees in 54 patients (age range 21-82 years; mean 36 years) were prospectively evaluated by using sagittal 3D FIESTA and sagittal fat-suppressed 3D SPGR sequences. Articular cartilage lesions were graded on MRI and during arthroscopy with a modified Noyes scoring system. Sensitivity, specificity, and accuracy were assessed. Interobserver agreement was determined with {kappa} statistics. Results: The performance of 3D FIESTA sequences (sensitivity, specificity, and accuracy were 80, 94, and 92%, respectively, for reader 1 and 76, 94, and 90%, respectively, for reader 2) was similar to that of fat-suppressed 3D SPGR sequences (sensitivity, specificity, and accuracy were 82, 92, and 90%, respectively, for reader 1 and 82, 90, and 88%, respectively, for reader 2) in the detection of knee articular cartilage lesions. The interobserver agreement varied from fair to good to excellent (kappa values from 0.43-0.83). Conclusion: 3D FIESTA has good diagnostic performance, comparable with fat-suppressed 3D SPGR in evaluating knee cartilage lesions, and it can be incorporated into routine knee MRI protocols due to the short acquisition time.

  5. Prospective comparison of 3D FIESTA versus fat-suppressed 3D SPGR MRI in evaluating knee cartilage lesions

    International Nuclear Information System (INIS)

    Li, X.; Yu, C.; Wu, H.; Daniel, K.; Hu, D.; Xia, L.; Pan, C.; Xu, A.; Hu, J.; Wang, L.; Peng, W.; Li, F.

    2009-01-01

    Aim: To prospectively compare the accuracy of three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) sequences with that of fat-suppressed three-dimensional spoiled gradient-recalled (3D SPGR) in the diagnosis of knee articular cartilage lesions, using arthroscopy as the reference standard. Materials and methods: Fifty-eight knees in 54 patients (age range 21-82 years; mean 36 years) were prospectively evaluated by using sagittal 3D FIESTA and sagittal fat-suppressed 3D SPGR sequences. Articular cartilage lesions were graded on MRI and during arthroscopy with a modified Noyes scoring system. Sensitivity, specificity, and accuracy were assessed. Interobserver agreement was determined with κ statistics. Results: The performance of 3D FIESTA sequences (sensitivity, specificity, and accuracy were 80, 94, and 92%, respectively, for reader 1 and 76, 94, and 90%, respectively, for reader 2) was similar to that of fat-suppressed 3D SPGR sequences (sensitivity, specificity, and accuracy were 82, 92, and 90%, respectively, for reader 1 and 82, 90, and 88%, respectively, for reader 2) in the detection of knee articular cartilage lesions. The interobserver agreement varied from fair to good to excellent (kappa values from 0.43-0.83). Conclusion: 3D FIESTA has good diagnostic performance, comparable with fat-suppressed 3D SPGR in evaluating knee cartilage lesions, and it can be incorporated into routine knee MRI protocols due to the short acquisition time.

  6. Fire suppression as a thermal implosion

    Science.gov (United States)

    Novozhilov, Vasily

    2017-01-01

    The present paper discusses the possibility of the thermal implosion scenario. This process would be a reverse of the well known thermal explosion (autoignition) phenomenon. The mechanism for thermal implosion scenario is proposed which involves quick suppression of the turbulent diffusion flame. Classical concept of the thermal explosion is discussed first. Then a possible scenario for the reverse process (thermal implosion) is discussed and illustrated by a relevant mathematical model. Based on the arguments presented in the paper, thermal implosion may be observed as an unstable equilibrium point on the generalized Semenov diagram for turbulent flame, however this hypothesis requires ultimate experimental confirmation.

  7. Applications of zero-suppressed decision diagrams

    CERN Document Server

    Sasao, Tsutomu

    2014-01-01

    A zero-suppressed decision diagram (ZDD) is a data structure to represent objects that typically contain many zeros. Applications include combinatorial problems, such as graphs, circuits, faults, and data mining. This book consists of four chapters on the applications of ZDDs. The first chapter by Alan Mishchenko introduces the ZDD. It compares ZDDs to BDDs, showing why a more compact representation is usually achieved in a ZDD. The focus is on sets of subsets and on sum-of-products (SOP) expressions. Methods to generate all the prime implicants (PIs), and to generate irredundant SOPs are show

  8. Experimental Status Of $J/\\psi$ Suppression

    CERN Document Server

    Kluberg, L; Alessandro, B; Alexa, C; Arnaldi, R; Astruc, J; Atayan, M; Baglin, C; Baldit, A; Bedjidian, M; Bellaiche, F; Beolè, S; Boldea, V; Bordalo, P; Bussière, A; Capelli,L; Capony, V; Casagrande, L; Castor, J; Chambon, T; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constans, N; Constantinescu, S; Cruz, J; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Filippov, S N; Fleuret, F; Force, P; Gallio, M; Gavrilov, Y K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanyan, H; Hakobyan, R; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kurepin, A B; Le Bornec, Y; Lourenrço, C; Macciotta, P; Mac Cormick, M; Marzari- Chiesa, A; Masera, M; Masoni, A; Mehrabyan, S; Monteno, M; Mourgues, S; Musso, A; Ohlsson-Malek, F; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Puddu, G; Quintans, C; Racca, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Ropotar, I; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Silva, S; Sitta, M; Soave, C; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N

    2001-01-01

    The most recent results obtained by experiment NA50 show that the $J /\\psi$ cross-section per nucleon-nucleon collision in semi-peripheral Pb-Pb reactions is "normally" suppressed in the sense that it follows the trend already observed from p-p and up to the most central S-U reactions. A clear change of behaviour is observed for more central Pb-Pb collisions which could be due to the transition of normal nuclear matter to its predicted Quark-Gluon Plasma state

  9. Improved attractants for enhancing tsetse fly suppression

    International Nuclear Information System (INIS)

    2003-09-01

    At the initiation of this co-ordinated research project (CRP), the available visually attractant devices and odours for entomological monitoring and for suppression of tsetse fly populations were not equally effective against all economically important tsetse fly species. For species like G. austeni, G. brevipalpis, G. swynnertoni and some species of the PALPALIS-group of tsetse flies no sufficiently effective combinations of visual or odour attractants were available for efficient suppression and standardized monitoring as part of an operational integrated intervention campaign against the tsetse and trypanosomosis (T and T) problem. The Co-ordinated Research Project on Improved Attractants for Enhancing the Efficiency of Tsetse Fly Suppression Operations and Barrier Systems used in Tsetse Control/Eradication Campaigns involved (a) the identification, synthesis and provision of candidate kairomones, their analogues and of dispensers; (b) laboratory screening of synthesised candidate kairomones through electrophysiological studies and wind tunnel experiments; (c) field tests of candidate kairomones alone or as part of odour blends, in combination with available and or new trap designs; and (d) analysis of hydrocarbons that influence tsetse sexual behaviour. The CRP accomplished several main objectives, namely: - The screening of new structurally related compounds, including specific stereoisomers, of known tsetse attractants resulted in the identification of several new candidate odour attractants with promising potential. - An efficient two-step synthetic method was developed for the pilot plant scale production of 3-n-propyphenol, synergistic tsetse kairomone component. - Electrophysiological experiments complemented with wind tunnel studies provided an efficient basis for the laboratory screening of candidate attractants prior to the initiation of laborious field tests. - New traps were identified and modifications of existing traps were tested for some species

  10. Pressure suppression system for a nuclear reactor

    International Nuclear Information System (INIS)

    Jost, N.

    1977-01-01

    The invention pertains to a pressure suppression system for PWR reactors where the parts enclosing the primary coolant are contained in two pressure-tight separate chambers. According to the invention, these chambers are partly filled with water and are connected with each other below the water surface. This way, gases cannot escape from the containment, not even if a valve and a line are damaged at the same time, as the vapours released condensate in the water of at least one of the other chambers. (HP) [de

  11. Fractional order absolute vibration suppression (AVS) controllers

    Science.gov (United States)

    Halevi, Yoram

    2017-04-01

    Absolute vibration suppression (AVS) is a control method for flexible structures. The first step is an accurate, infinite dimension, transfer function (TF), from actuation to measurement. This leads to the collocated, rate feedback AVS controller that in some cases completely eliminates the vibration. In case of the 1D wave equation, the TF consists of pure time delays and low order rational terms, and the AVS controller is rational. In all other cases, the TF and consequently the controller are fractional order in both the delays and the "rational parts". The paper considers stability, performance and actual implementation in such cases.

  12. The relation of weight suppression and BMI to bulimic symptoms.

    Science.gov (United States)

    Butryn, Meghan L; Juarascio, Adrienne; Lowe, Michael R

    2011-11-01

    High levels of weight suppression have been associated with greater binge eating and weight gain as well as poorer treatment outcome in bulimia nervosa. This study examined the relationship between weight suppression and bulimia nervosa symptoms and explored how weight suppression might interact with body mass index (BMI) in accounting for level of symptomatology at presentation for treatment. Participants were 64 women with threshold or sub-threshold bulimia nervosa. A clinical interview assessed binge eating and purging. Weight suppression and the interaction between BMI and weight suppression predicted frequency of binge eating such that participants with low BMI and high weight suppression engaged in the most binge eating. High levels of weight suppression also predicted more frequent purging. Additional research is warranted to examine mediators of these relationships. Copyright © 2010 Wiley Periodicals, Inc.

  13. Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil.

    Science.gov (United States)

    Bryant, Victoria L; Elias, Roy M; McCarthy, Susan M; Yeatman, Timothy J; Alexandrow, Mark G

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as backup initiation sites under conditions of replicative stress. The current study provides definitive evidence that cosuppression of the excess/backup MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared with drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are nontumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when cosuppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. These studies demonstrate that suppressing the backup complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers. ©2015 American Association for Cancer Research.

  14. INFLUENCE OF MODIFIED BIOFLAVONOIDS UPON EFFECTOR LYMPHOCYTES IN MURINE MODEL OF CONTACT SENSITIVITY

    Directory of Open Access Journals (Sweden)

    D. Z. Albegova

    2015-01-01

    Full Text Available Contact sensitivity reaction (CSR to 2,4-dinitrofluorobenzene (DNFB in mice is a model of in vivo immune response, being an experimental analogue to contact dermatitis in humans. CSR sensitization phase begins after primary contact with antigen, lasting for 10-15 days in humans, and 5-7 days, in mice. Repeated skin exposure to the sensitizing substance leads to its recognition and triggering immune inflammatory mechanisms involving DNFB-specific effector T lymphocytes. The CSR reaches its maximum 18-48 hours after re-exposure to a hapten. There is only scarce information in the literature about effects of flavonoids on CSR, including both stimulatory and inhibitory effects. Flavonoids possessed, predominantly, suppressive effects against the CSR development. In our laboratory, a model of contact sensitivity was reproduced in CBA mice by means of cutaneous sensitization by 2,4-dinitrofluorobenzene. The aim of the study was to identify the mechanisms of immunomodulatory action of quercetin dihydrate and modified bioflavonoids, using the method of adoptive transfer contact sensitivity by splenocytes and T-lymphocytes. As shown in our studies, a 30-min pre-treatment of splenocytes and T-lymphocytes from sensitized mice with modified bioflavonoids before the cell transfer caused complete prevention of contact sensitivity reaction in syngeneic recipient mice. Meanwhile, this effect was not associated with cell death induction due to apoptosis or cytotoxicity. Quercetin dihydrate caused only partially suppression the activity of adaptively formed T-lymphocytes, the contact sensitivity effectors. It was shown that the modified bioflavonoid more stronger suppress adoptive transfer of contact sensitivity in comparison with quercetin dehydrate, without inducing apoptosis of effector cells. Thus, the modified bioflavonoid is a promising compound for further studies in a model of contact sensitivity, due to its higher ability to suppress transfer of CSR with

  15. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    . Background. Many countries are becoming culturally diverse, but healthcare systems and nursing education often remain mono-cultural and focused on the norms and needs of the majority culture. To meet the needs of all members of multicultural societies, nurses need to develop cultural sensitivity......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students...... and incorporate this into caregiving. Method. A Gadamerian hermeneutic phenomenological approach was adopted. Data were collected in 2004 by using in-depth conversational interviews and analysed using the Turner method. Findings. Developing cultural sensitivity involves a complex interplay between becoming...

  16. Spontaneous baroreflex sensitivity

    DEFF Research Database (Denmark)

    Barthel, Petra; Bauer, Axel; Müller, Alexander

    2012-01-01

    Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming thes...

  17. Reinstatement of Conditioned Suppression in Mice

    Directory of Open Access Journals (Sweden)

    Trinette Dirikx

    2006-03-01

    Full Text Available Return of fear after successful exposure therapy calls for a better understanding of the mechanisms of relapse. Classical conditioning research provides a useful framework for conceptualising the acquisition, extinction and reappearance of fear. The present paper focuses on reinstatement, the return of extinguished conditioned responses due to the experience of one or more unconditioned stimuli (USs after extinction. This phenomenon illustrates that unpredictable USs can lead to a return of fear after successful exposure. The data we present is one of the first demonstrations that conditioned suppression of instrumental behaviour can be used as an index of classical conditioning in laboratory mice. The procedure proves to be a promising instrument for assessing fear in mice, both in the context of research aimed at unravelling the functional characteristics of learning and memory in healthy mice and in the context of research aimed at unravelling the neurobiological substrate of psychiatric disorders, e.g., in studies with transgenic and knockout mice. Using this procedure, we report the first observation of reinstatement of conditioned suppression in this species.

  18. Suppressive and immunoprotective functions of Tregs

    Directory of Open Access Journals (Sweden)

    Pushpa ePandiyan

    2011-11-01

    Full Text Available CD4+CD25+Foxp3+ T lymphocytes, known as regulatory T cells or Tregs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of Tregs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells (APCs; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4+ effector T cells are directly inhibited by Tregs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion (PCD; and 4. Contrary to the current view, we discuss new evidence that Tregs, similar to other T cells lineages, can promote protective immune responses in certain infectious contexts (Pandiyan et al. 2011; Chen et al 2011. Although these points are at variance to varying degrees with the standard model of Treg behavior, we will recount developing findings that support these new concepts.

  19. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  20. Optimal digital filtering for tremor suppression.

    Science.gov (United States)

    Gonzalez, J G; Heredia, E A; Rahman, T; Barner, K E; Arce, G R

    2000-05-01

    Remote manually operated tasks such as those found in teleoperation, virtual reality, or joystick-based computer access, require the generation of an intermediate electrical signal which is transmitted to the controlled subsystem (robot arm, virtual environment, or a cursor in a computer screen). When human movements are distorted, for instance, by tremor, performance can be improved by digitally filtering the intermediate signal before it reaches the controlled device. This paper introduces a novel tremor filtering framework in which digital equalizers are optimally designed through pursuit tracking task experiments. Due to inherent properties of the man-machine system, the design of tremor suppression equalizers presents two serious problems: 1) performance criteria leading to optimizations that minimize mean-squared error are not efficient for tremor elimination and 2) movement signals show ill-conditioned autocorrelation matrices, which often result in useless or unstable solutions. To address these problems, a new performance indicator in the context of tremor is introduced, and the optimal equalizer according to this new criterion is developed. Ill-conditioning of the autocorrelation matrix is overcome using a novel method which we call pulled-optimization. Experiments performed with artificially induced vibrations and a subject with Parkinson's disease show significant improvement in performance. Additional results, along with MATLAB source code of the algorithms, and a customizable demo for PC joysticks, are available on the Internet at http:¿tremor-suppression.com.

  1. Tagging and suppression of pileup jets

    CERN Document Server

    The ATLAS collaboration

    2014-01-01

    The suppression of pileup jets has been a crucial component of many physics analyses using 2012 LHC proton-proton collisions. In ATLAS, tracking information has been used to calculate a variable called the jet-vertex-fraction, which is the fraction of the total mo- mentum of tracks in the jet which is associated to the primary vertex. Imposing a minimum on this variable rejects the majority of pileup jets, but leads to hard-scatter jet efficiencies that depend on the number of reconstructed primary vertices in the event ($N_{Vtx}$). In this note, new track-based variables to suppress pileup jets are developed in such a way that the resulting hard-scatter jet efficiency is stable as a function of $N_{Vtx}$. A multivariate combina- tion of two such variables called the jet-vertex-tagger is constructed. In addition, it is shown that jet-vertex association can be applied to large-R jets, providing a track-based grooming technique that is as powerful as calorimeter-based trimming but based on complementary trackin...

  2. Wireless Inductive Power Device Suppresses Blade Vibrations

    Science.gov (United States)

    Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

    2011-01-01

    Vibration in turbomachinery can cause blade failures and leads to the use of heavier, thicker blades that result in lower aerodynamic efficiency and increased noise. Metal and/or composite fatigue in the blades of jet engines has resulted in blade destruction and loss of lives. Techniques for suppressing low-frequency blade vibration, such as gtuned circuit resistive dissipation of vibratory energy, h or simply "passive damping," can require electronics incorporating coils of unwieldy dimensions and adding unwanted weight to the rotor. Other approaches, using vibration-dampening devices or damping material, could add undesirable weight to the blades or hub, making them less efficient. A wireless inductive power device (WIPD) was designed, fabricated, and developed for use in the NASA Glenn's "Dynamic Spin Rig" (DSR) facility. The DSR is used to simulate the functionality of turbomachinery. The relatively small and lightweight device [10 lb (approx.=4.5 kg)] replaces the existing venerable and bulky slip-ring. The goal is the eventual integration of this technology into actual turbomachinery such as jet engines or electric power generators, wherein the device will facilitate the suppression of potentially destructive vibrations in fan blades. This technology obviates slip rings, which require cooling and can prove unreliable or be problematic over time. The WIPD consists of two parts: a remote element, which is positioned on the rotor and provides up to 100 W of electrical power to thin, lightweight piezoelectric patches strategically placed on/in fan blades; and a stationary base unit that wirelessly communicates with the remote unit. The base unit supplies inductive power, and also acts as an input and output corridor for wireless measurement, and active control command to the remote unit. Efficient engine operation necessitates minimal disturbance to the gas flow across the turbine blades in any effort to moderate blade vibration. This innovation makes it

  3. Analysis of a Mark II containment structure for hydrodynamic loads in suppression pool

    International Nuclear Information System (INIS)

    Bedrosian, B.

    1978-01-01

    During pressure-relief modes of BWR plant operation forcing signals are introduced into the suppression pool at discrete locations: exit nozzles of SRV discharge pipes (quenchers or ramsheads). These forcing signals are transmitted through the water of the suppression pool and, after reaching the pool boundaries, act as loadings on the containment structure wetted perimeter. The response of the containment structure is influenced by the presence of water as it interacts with the structure during application of the load. An adequate analysis must account for fluid-structure interaction (FSI) effects. This paper presents an exact formulation for solving the problem. FSI effects may become significant for a given geometry if the time history of loading and the dynamic properties of the coupled fluid-structure system satisfy a defined (system related) relationship. Results of analyses and parametric/sensitivity studies performed for the steel containment structure of an 1100 Mwe BWR nuclear plant of Mark II configuration are presented. (Author)

  4. Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy

    Directory of Open Access Journals (Sweden)

    Ryota Matsubara

    2017-06-01

    Full Text Available Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.

  5. Production and efficiency of large wildland fire suppression effort: A stochastic frontier analysis.

    Science.gov (United States)

    Katuwal, Hari; Calkin, David E; Hand, Michael S

    2016-01-15

    This study examines the production and efficiency of wildland fire suppression effort. We estimate the effectiveness of suppression resource inputs to produce controlled fire lines that contain large wildland fires using stochastic frontier analysis. Determinants of inefficiency are identified and the effects of these determinants on the daily production of controlled fire line are examined. Results indicate that the use of bulldozers and fire engines increase the production of controlled fire line, while firefighter crews do not tend to contribute to controlled fire line production. Production of controlled fire line is more efficient if it occurs along natural or built breaks, such as rivers and roads, and within areas previously burned by wildfires. However, results also indicate that productivity and efficiency of the controlled fire line are sensitive to weather, landscape and fire characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Contribution of suppression difficulty and lessons learned in forecasting fire suppression operations productivity: A methodological approach

    Science.gov (United States)

    Francisco Rodríguez y Silva; Armando González-Cabán

    2016-01-01

    We propose an economic analysis using utility and productivity, and efficiency theories to provide fire managers a decision support tool to determine the most efficient fire management programs levels. By incorporating managers’ accumulated fire suppression experiences (capitalized experience) in the analysis we help fire managers...

  7. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

    Science.gov (United States)

    Arnold, Amy C.

    2014-01-01

    The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. PMID:25260611

  8. Mincle suppresses Toll-like receptor 4 activation.

    Science.gov (United States)

    Greco, Stephanie H; Mahmood, Syed Kashif; Vahle, Anne-Kristin; Ochi, Atsuo; Batel, Jennifer; Deutsch, Michael; Barilla, Rocky; Seifert, Lena; Pachter, H Leon; Daley, Donnele; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Miller, George

    2016-07-01

    Regulation of Toll-like receptor responses is critical for limiting tissue injury and autoimmunity in both sepsis and sterile inflammation. We found that Mincle, a C-type lectin receptor, regulates proinflammatory Toll-like receptor 4 signaling. Specifically, Mincle ligation diminishes Toll-like receptor 4-mediated inflammation, whereas Mincle deletion or knockdown results in marked hyperresponsiveness to lipopolysaccharide in vitro, as well as overwhelming lipopolysaccharide-mediated inflammation in vivo. Mechanistically, Mincle deletion does not up-regulate Toll-like receptor 4 expression or reduce interleukin 10 production after Toll-like receptor 4 ligation; however, Mincle deletion decreases production of the p38 mitogen-activated protein kinase-dependent inhibitory intermediate suppressor of cytokine signaling 1, A20, and ABIN3 and increases expression of the Toll-like receptor 4 coreceptor CD14. Blockade of CD14 mitigates the increased sensitivity of Mincle(-/-) leukocytes to Toll-like receptor 4 ligation. Collectively, we describe a major role for Mincle in suppressing Toll-like receptor 4 responses and implicate its importance in nonmycobacterial models of inflammation. © Society for Leukocyte Biology.

  9. Suppression of Face Perception during Saccadic Eye Movements

    Directory of Open Access Journals (Sweden)

    Mehrdad Seirafi

    2014-01-01

    Full Text Available Lack of awareness of a stimulus briefly presented during saccadic eye movement is known as saccadic omission. Studying the reduced visibility of visual stimuli around the time of saccade—known as saccadic suppression—is a key step to investigate saccadic omission. To date, almost all studies have been focused on the reduced visibility of simple stimuli such as flashes and bars. The extension of the results from simple stimuli to more complex objects has been neglected. In two experimental tasks, we measured the subjective and objective awareness of a briefly presented face stimuli during saccadic eye movement. In the first task, we measured the subjective awareness of the visual stimuli and showed that in most of the trials there is no conscious awareness of the faces. In the second task, we measured objective sensitivity in a two-alternative forced choice (2AFC face detection task, which demonstrated chance-level performance. Here, we provide the first evidence of complete suppression of complex visual stimuli during the saccadic eye movement.

  10. Polarization Sensitive Coherent Raman Measurements of DCVJ

    Science.gov (United States)

    Anderson, Josiah; Cooper, Nathan; Lawhead, Carlos; Shiver, Tegan; Ujj, Laszlo

    2014-03-01

    Coherent Raman spectroscopy which recently developed into coherent Raman microscopy has been used to produce label free imaging of thin layers of material and find the spatial distributions of certain chemicals within samples, e.g. cancer cells.(1) Not all aspects of coherent scattering have been used for imaging. Among those for example are special polarization sensitive measurements. Therefore we have investigated the properties of polarization sensitive CARS spectra of a highly fluorescent molecule, DCVJ.(2) Spectra has been recorded by using parallel polarized and perpendicular polarized excitations. A special polarization arrangement was developed to suppress the non-resonant background scattering from the sample. These results can be used to improve the imaging properties of a coherent Raman microscope in the future. This is the first time coherent Raman polarization sensitive measurements have been used to characterize the vibrational modes of DCVJ. 1: K. I. Gutkowski, et al., ``Fluorescence of dicyanovinyl julolidine in a room temperature ionic liquid '' Chemical Physics Letters 426 (2006) 329 - 333 2: Fouad El-Diasty, ``Coherent anti-Stokes Raman scattering: Spectroscopy and microscopy'' Vibrational Spectroscopy 55 (2011) 1-37

  11. WHAT IF (Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Iulian N. BUJOREANU

    2011-01-01

    Full Text Available Sensitivity analysis represents such a well known and deeply analyzed subject that anyone to enter the field feels like not being able to add anything new. Still, there are so many facets to be taken into consideration.The paper introduces the reader to the various ways sensitivity analysis is implemented and the reasons for which it has to be implemented in most analyses in the decision making processes. Risk analysis is of outmost importance in dealing with resource allocation and is presented at the beginning of the paper as the initial cause to implement sensitivity analysis. Different views and approaches are added during the discussion about sensitivity analysis so that the reader develops an as thoroughly as possible opinion on the use and UTILITY of the sensitivity analysis. Finally, a round-up conclusion brings us to the question of the possibility of generating the future and analyzing it before it unfolds so that, when it happens it brings less uncertainty.

  12. Sensitivity Analysis Without Assumptions.

    Science.gov (United States)

    Ding, Peng; VanderWeele, Tyler J

    2016-05-01

    Unmeasured confounding may undermine the validity of causal inference with observational studies. Sensitivity analysis provides an attractive way to partially circumvent this issue by assessing the potential influence of unmeasured confounding on causal conclusions. However, previous sensitivity analysis approaches often make strong and untestable assumptions such as having an unmeasured confounder that is binary, or having no interaction between the effects of the exposure and the confounder on the outcome, or having only one unmeasured confounder. Without imposing any assumptions on the unmeasured confounder or confounders, we derive a bounding factor and a sharp inequality such that the sensitivity analysis parameters must satisfy the inequality if an unmeasured confounder is to explain away the observed effect estimate or reduce it to a particular level. Our approach is easy to implement and involves only two sensitivity parameters. Surprisingly, our bounding factor, which makes no simplifying assumptions, is no more conservative than a number of previous sensitivity analysis techniques that do make assumptions. Our new bounding factor implies not only the traditional Cornfield conditions that both the relative risk of the exposure on the confounder and that of the confounder on the outcome must satisfy but also a high threshold that the maximum of these relative risks must satisfy. Furthermore, this new bounding factor can be viewed as a measure of the strength of confounding between the exposure and the outcome induced by a confounder.

  13. Sensitivities of ionic explosives

    Science.gov (United States)

    Politzer, Peter; Lane, Pat; Murray, Jane S.

    2017-03-01

    We have investigated the relevance for ionic explosive sensitivity of three factors that have been demonstrated to be related to the sensitivities of molecular explosives. These are (1) the maximum available heat of detonation, (2) the amount of free space per molecule (or per formula unit) in the crystal lattice and (3) specific features of the electrostatic potential on the molecular or ionic surface. We find that for ionic explosives, just as for molecular ones, there is an overall tendency for impact sensitivity to increase as the maximum detonation heat release is greater. This means that the usual emphasis upon designing explosives with large heats of detonation needs to be tempered somewhat. We also show that a moderate detonation heat release does not preclude a high level of detonation performance for ionic explosives, as was already demonstrated for molecular ones. Relating the free space per formula unit to sensitivity may require a modified procedure for ionic explosives; this will continue to be investigated. Finally, an encouraging start has been made in linking impact sensitivities to the electrostatic potentials on ionic surfaces, although limited so far to ammonium salts.

  14. Managing a sensitive project

    International Nuclear Information System (INIS)

    Etcheber, Pascal

    1998-01-01

    A 'sensitive' project needs to be managed differently from a 'normal' project. This statement might seem simple enough. However, it does not seem to be a simple task to prove it in twenty minutes. This paper is an attempt to share with the audience some of the experiences the company had dealing with sensitive projects. It describes what a sensitive project is, though of all people, the 'nuclear' should know. Then the common mistakes are described, that are made in the hoping that some personal experiences are recognised. Finally the company's strategy is shown, how we foster third party support and the main tools to be used. Ultimately, success is ensured by having a sufficient quantity of allies. A sensitive project does not die because it has too many opponents, but because it has too few allies. Finding and helping allies to act is the thrust of our activity. It enables sensitive projects which deserve to succeed to do so, where traditional management fails miserably

  15. Theobromine inhibits sensory nerve activation and cough.

    Science.gov (United States)

    Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J

    2005-02-01

    Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

  16. The generation and suppression of synchrotron sidebands

    International Nuclear Information System (INIS)

    Warren, R.W.; Goldstein, J.C.

    1987-01-01

    Computer simulations of FEL lasing differ in the degree to which they approximate real experiments. One of the FEL codes used extensively at Los Alamos takes account of the features of each electron micropulse and follows the growth and saturation of the optical micropulse. With no additional adjustments, this code displays the development of sidebands and demonstrates their control when optical filters of various kinds are used. Other codes that do not include a description of the micropulse do not automatically display sidebands but need to have artificial noise of some kind added. This is not unexpected because sidebands are generated by an FEL instability; instabilities, in general, need some kind of initiating disturbance. In this paper we: identify the disturbance that triggers the instability in the pulse code; discuss a practical way to suppress the instability without using filters; compare these results with experiments; and discuss these findings. 22 refs., 9 figs

  17. Probe suppression in conformal phased array

    CERN Document Server

    Singh, Hema; Neethu, P S

    2017-01-01

    This book considers a cylindrical phased array with microstrip patch antenna elements and half-wavelength dipole antenna elements. The effect of platform and mutual coupling effect is included in the analysis. The non-planar geometry is tackled by using Euler's transformation towards the calculation of array manifold. Results are presented for both conducting and dielectric cylinder. The optimal weights obtained are used to generate adapted pattern according to a given signal scenario. It is shown that array along with adaptive algorithm is able to cater to an arbitrary signal environment even when the platform effect and mutual coupling is taken into account. This book provides a step-by-step approach for analyzing the probe suppression in non-planar geometry. Its detailed illustrations and analysis will be a useful text for graduate and research students, scientists and engineers working in the area of phased arrays, low-observables and stealth technology.

  18. Void growth suppression by dislocation impurity atmospheres

    International Nuclear Information System (INIS)

    Weertman, J.; Green, W.V.

    1976-01-01

    A detailed calculation is given of the effect of an impurity atmosphere on void growth under irradiation damage conditions. Norris has proposed that such an atmosphere can suppress void growth. The hydrostatic stress field of a dislocation that is surrounded by an impurity atmosphere was found and used to calculate the change in the effective radius of a dislocation line as a sink for interstitials and vacancies. The calculation of the impurity concentration in a Cottrell cloud takes into account the change in hydrostatic pressure produced by the presence of the cloud itself. It is found that void growth is eliminated whenever dislocations are surrounded by a condensed atmosphere of either oversized substitutional impurity atoms or interstitial impurity atoms. A condensed atmosphere will form whenever the average impurity concentration is larger than a critical concentration

  19. In-beam background suppression shield

    DEFF Research Database (Denmark)

    Santoro, V.; Cai, Xiao Xiao; DiJulio, D. D.

    2015-01-01

    The long (3 ms) proton pulse of the European Spallation Source (ESS) gives rise to unique and potentially high backgrounds for the instrument suite. In such a source an instrument's capabilities will be limited by its Signal to Noise (S/N) ratio. The instruments with a direct view of the moderator......, which do not use a bender to help mitigate the fast neutron background, are the most challenging. For these beam lines we propose the innovative shielding of placing blocks of material directly into the guide system, which allow a minimum attenuation of the cold and thermal fluxes relative...... to the background suppression. This shielding configuration has been worked into a beam line model using Geant4. We study particularly the advantages of single crystal sapphire and silicon blocks....

  20. Suppression of fertility in adult cats

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Wehrend, A.; Georgiev, P.

    2014-01-01

    /needed? (iii) sex of the animal? New effective and available methods for hormonal contraception include melatonin implants for short-term post ponement of oestrus in adult queens and slow-release GnRH-agonist implants containing deslorelin (Suprelorin®) for short- and long-term contraception in male and female......Contents: Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible......, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific...

  1. Suppression of coffee ring: (Particle) size matters

    Science.gov (United States)

    Bansal, Lalit; Seth, Pranjal; Murugappan, Bhubesh; Basu, Saptarshi

    2018-05-01

    Coffee ring patterns in drying sessile droplets are undesirable in various practical applications. Here, we experimentally demonstrate that on hydrophobic substrates, the coffee ring can be suppressed just by increasing the particle diameter. Particles with larger size flocculate within the evaporation timescale, leading to a significant gravimetric settling (for Pe > 1) triggering a uniform deposit. Interestingly, the transition to a uniform deposit is found to be independent of the internal flow field and substrate properties. Flocculation of particles also alters the particle packing at the nanoscale resulting in order to disorder transitions. In this letter, we exhibit a physical exposition on how particle size affects morphodynamics of the droplet drying at macro-nano length scales.

  2. Are Patents used to Suppress Useful Technology?

    DEFF Research Database (Denmark)

    Howells, John

    2006-01-01

    of innovation, other than in the trivial sense of excluding third parties from the right to develop the technology covered by the patent? There are many references to this possibility in the management, economic and legal literatures, but two highly-cited papers stand out for grounding their claims of corporate......This article examines the evidence behind claims that innovation is hindered or blocked (termed technology suppression) by corporations' use of patents. In other words, are there ways in which the exploitation of the exclusive development right of the patent can be shown to retard the process...... and the difference between economic monopoly and an exclusive right. It is argued here that what is at issue in this work is the proper function of the patent institution. It is shown early in this paper that the understanding of the patent institution as a system of development prospects makes better sense...

  3. Active vibration suppression of helicopter horizontal stabilizers

    Science.gov (United States)

    Cinquemani, Simone; Cazzulani, Gabriele; Resta, Ferruccio

    2017-04-01

    Helicopters are among the most complex machines ever made. While ensuring high performance from the aeronautical point of view, they are not very comfortable due to vibration mainly created by the main rotor and by the interaction with the surrounding air. One of the most solicited structural elements of the vehicle are the horizontal stabilizers. These elements are particularly stressed because of their composite structure which, while guaranteeing lightness and strength, is characterized by a low damping. This work makes a preliminary analysis on the dynamics of the structure and proposes different solutions to actively suppress vibrations. Among them, the best in terms of the relationship between performance and weight / complexity of the system is that based on inertial actuators mounted on the inside of the horizontal stabilizers. The work addresses the issue of the design of the device and its use in the stabilizer from both the numerical and the experimental points of view.

  4. Ion suppression from blood collection devices

    DEFF Research Database (Denmark)

    Hasselstrøm, Jørgen Bo; Sejr Gothelf, Aase

    The aim of the study was to examine the variation in ion suppression in ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS-MS) methods when using different blood collection devices. Three different methods measuring 18 antidepressants and antipsychotics in total were...... Terumo, S-monovette from Sarstedt, Vacuette from Greiner Bio-One and three BD Vacutainer serum tubes from BD. These seven different blood collection devices were used to withdraw blood from five healthy drug free donors (n=35) in random order. The samples were centrifuged and serum from each sample...... by UHPLC-MS-MS using three different gradients (Group I, II and III). The analytes in group I was measured on an Agilent 6460 mass spectrometer and group II and III were measured on an Agilent 6410 mass spectrometer both utilizing positive electrospray ionization. The experiments demonstrated significant...

  5. Neutrino wave function and oscillation suppression

    International Nuclear Information System (INIS)

    Dolgov, A.D.; Lychkovskiy, O.V.; Mamonov, A.A.; Okun, L.B.; Schepkin, M.G.

    2005-01-01

    We consider a thought experiment, in which a neutrino is produced by an electron on a nucleus in a crystal. The wave function of the oscillating neutrino is calculated assuming that the electron is described by a wave packet. If the electron is relativistic and the spatial size of its wave packet is much larger than the size of the crystal cell, then the wave packet of the produced neutrino has essentially the same size as the wave packet of the electron. We investigate the suppression of neutrino oscillations at large distances caused by two mechanisms: (1) spatial separation of wave packets corresponding to different neutrino masses; (2) neutrino energy dispersion for given neutrino mass eigenstates. We resolve the contributions of these two mechanisms. (orig.)

  6. Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

    Directory of Open Access Journals (Sweden)

    Niczyporuk Aneta

    2016-12-01

    Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

  7. The effect of caffeine and adenine on radiation induced suppression of DNA synthesis, and cell survival

    International Nuclear Information System (INIS)

    Wilcoxson, L.T.; Griffiths, T.D.

    1984-01-01

    Exposure of cultured mammalian cells to ionizing radiation or UV light results in a transient decrease in the rate of DNA synthesis. This depression in synthetic rate may be attenuated or deferred via a post-irradiation treatment with caffeine or adenine. It has been suggested that this attenuation may increase the fixation of damage and, therefore, increase radiation sensitivity. However, it has been previously reported that, for V79 cells treated with caffeine or adenine, no correlation exists between the extent of depression and cell survival. The present investigation expands upon these findings by examining the effect of caffeine or adenine post-irradiation treatment on two cell lines with normal UV sensitivity, mouse 3T3 and CHO AA8 cells, and one UV sensitive cell line, CHO UV5 cells. Both caffeine and adenine have been found to reduce, or delay, the suppression in DNA synthesis in all three cell lines. Surprisingly, caffeine appeared to induced even the UV5 cells to recover DNA synthetic ability. The amount of reduction in suppression of DNA synthesis, however, varies between the different cell lines and no consistent relationship with cell survival has emerged

  8. Suppressive effects of ketamine on macrophage functions

    International Nuclear Information System (INIS)

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M.

    2005-01-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 μM ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 μM, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 μM, did not affect the chemotactic activity of macrophages. Administration of 1000 μM ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-α, IL-1β, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-α, IL-1β, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-α, IL-1β, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 μM) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity

  9. Rituximab selectively suppresses specific islet antibodies.

    Science.gov (United States)

    Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

    2011-10-01

    The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

  10. Suppression of soil nitrification by plants.

    Science.gov (United States)

    Subbarao, Guntur Venkata; Yoshihashi, Tadashi; Worthington, Margaret; Nakahara, Kazuhiko; Ando, Yasuo; Sahrawat, Kanwar Lal; Rao, Idupulapati Madhusudhana; Lata, Jean-Christophe; Kishii, Masahiro; Braun, Hans-Joachim

    2015-04-01

    Nitrification, the biological oxidation of ammonium to nitrate, weakens the soil's ability to retain N and facilitates N-losses from production agriculture through nitrate-leaching and denitrification. This process has a profound influence on what form of mineral-N is absorbed, used by plants, and retained in the soil, or lost to the environment, which in turn affects N-cycling, N-use efficiency (NUE) and ecosystem health and services. As reactive-N is often the most limiting in natural ecosystems, plants have acquired a range of mechanisms that suppress soil-nitrifier activity to limit N-losses via N-leaching and denitrification. Plants' ability to produce and release nitrification inhibitors from roots and suppress soil-nitrifier activity is termed 'biological nitrification inhibition' (BNI). With recent developments in methodology for in-situ measurement of nitrification inhibition, it is now possible to characterize BNI function in plants. This review assesses the current status of our understanding of the production and release of biological nitrification inhibitors (BNIs) and their potential in improving NUE in agriculture. A suite of genetic, soil and environmental factors regulate BNI activity in plants. BNI-function can be genetically exploited to improve the BNI-capacity of major food- and feed-crops to develop next-generation production systems with reduced nitrification and N2O emission rates to benefit both agriculture and the environment. The feasibility of such an approach is discussed based on the progresses made. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Regorafenib suppresses sinusoidal obstruction syndrome in rats.

    Science.gov (United States)

    Okuno, Masayuki; Hatano, Etsuro; Nakamura, Kojiro; Miyagawa-Hayashino, Aya; Kasai, Yosuke; Nishio, Takahiro; Seo, Satoru; Taura, Kojiro; Uemoto, Shinji

    2015-02-01

    Sinusoidal obstruction syndrome (SOS), a form of drug-induced liver injury related to oxaliplatin treatment, is associated with postoperative morbidity after hepatectomy. This study aimed to examine the impact of regorafenib, the first small-molecule kinase inhibitor to show efficacy against metastatic colorectal cancer, on a rat model of SOS. Rats with monocrotaline (MCT)-induced SOS were divided into two groups according to treatment with either regorafenib (6 mg/kg) or vehicle alone, which were administered at 12 and 36 h, respectively, before MCT administration. Histopathologic examination and serum biochemistry tests were performed 48 h after MCT administration. Sinusoidal endothelial cells were evaluated by immunohistochemistry and electron microscopy. To examine whether regorafenib preserved remnant liver function, a 30% hepatectomy was performed in each group. The rats in the vehicle group displayed typical SOS features, whereas these features were suppressed in the regorafenib group. The total SOS scores were significantly lower in the regorafenib group than in the vehicle group. Immunohistochemistry and electron microscopy showed that regorafenib had a protective effect on sinusoidal endothelial cells. The postoperative survival rate after 7 d was significantly better in the regorafenib group than that in the vehicle group (26.7% versus 6.7%, P Regorafenib reduced the phosphorylation of extracellular signal-regulated kinase, which induced matrix metalloproteinase-9 (MMP-9) activation and decreased the activity of MMP-9, one of the crucial mediators of SOS development. Regorafenib suppressed MCT-induced SOS, concomitant with attenuating extracellular signal-regulated kinase phosphorylation, and MMP-9 activation, suggesting that regorafenib may be a favorable agent for use in combination with oxaliplatin-based chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Are Claims of Global Warming Being Suppressed?

    Science.gov (United States)

    Crowley, Thomas J.

    2006-02-01

    Over the last few years, I have heard many rumors that climate science relevant to the global warming discussion is being suppressed by the Bush Administration. One cannot do much about third-hand information. However, on 29 January, the New York Times published a front page article on NASA efforts to suppress statements about global warming by James Hansen, director of the NASA Goddard Institute for Space Studies. A claim by one government scientist, though, no matter how distinguished, still requires examples from other scientists before a general conclusion can be drawn about the overall scope of the problem. But if the charges are more widespread, then some government scientists might be reluctant to make such claims, because they might feel that their positions were jeopardized. Therefore, an alternate way may be needed to determine the scope of the issue, while still safeguarding government workers from possible retaliation. -On 30 January, Rep. Sherwood Boehlert (R-N.Y.), chairman of the U.S. House of Representatives Committee on Science, wrote a letter to NASA Administrator Michael Griffin addressing many of the concerns Crowley has raised. Boehlert wrote,``It ought to go without saying that government scientists must be free to describe their scientific conclusions and the implications of those conclusions to their fellow scientists, policymakers and the general public.'' He continued,``Good science cannot long persist in an atmosphere of intimidation. Political figures ought to be reviewing their public statements to make sure they are consistent with the best available science; scientists should not be reviewing their statements to make sure they are consistent with the current political orthodoxy.'' I commend Rep. Boehlert for his quick and clear statement of the importance of unfettered communication of science. -FRED SPILHAUS, Editor

  13. SUPPRESSION OF STAR FORMATION IN NGC 1266

    Energy Technology Data Exchange (ETDEWEB)

    Alatalo, Katherine; Lanz, Lauranne; Bitsakis, Theodoros; Appleton, Philip N.; Ogle, Patrick M. [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Lacy, Mark; Lonsdale, Carol J. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Nyland, Kristina; Meier, David S. [Physics Department, New Mexico Tech, Socorro, NM 87801 (United States); Cales, Sabrina L. [Department of Astronomy, Faculty of Physical and Mathematical Sciences, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Chang, Philip [Department of Physics, University of Wisconsin—Milwaukee, Milwaukee, WI 53201 (United States); Davis, Timothy A.; De Zeeuw, P. T. [European Southern Observatory, Karl-Schwarzschild-Str. 2, D-85748 Garching (Germany); Martín, Sergio, E-mail: kalatalo@ipac.caltech.edu [Institut de Radioastronomie Millimétrique, 300 Rue de la Piscine, Domaine Universitaire, F-38406 Saint Martin d' Hères (France)

    2015-01-01

    NGC 1266 is a nearby lenticular galaxy that harbors a massive outflow of molecular gas powered by the mechanical energy of an active galactic nucleus (AGN). It has been speculated that such outflows hinder star formation (SF) in their host galaxies, providing a form of feedback to the process of galaxy formation. Previous studies, however, indicated that only jets from extremely rare, high-power quasars or radio galaxies could impart significant feedback on their hosts. Here we present detailed observations of the gas and dust continuum of NGC 1266 at millimeter wavelengths. Our observations show that molecular gas is being driven out of the nuclear region at M-dot {sub out}≈110 M{sub ⊙} yr{sup –1}, of which the vast majority cannot escape the nucleus. Only 2 M {sub ☉} yr{sup –1} is actually capable of escaping the galaxy. Most of the molecular gas that remains is very inefficient at forming stars. The far-infrared emission is dominated by an ultra-compact (≲ 50 pc) source that could either be powered by an AGN or by an ultra-compact starburst. The ratio of the SF surface density (Σ{sub SFR}) to the gas surface density (Σ{sub H{sub 2}}) indicates that SF is suppressed by a factor of ≈50 compared to normal star-forming galaxies if all gas is forming stars, and ≈150 for the outskirt (98%) dense molecular gas if the central region is powered by an ultra-compact starburst. The AGN-driven bulk outflow could account for this extreme suppression by hindering the fragmentation and gravitational collapse necessary to form stars through a process of turbulent injection. This result suggests that even relatively common, low-power AGNs are able to alter the evolution of their host galaxies as their black holes grow onto the M-σ relation.

  14. Sunspot Light Walls Suppressed by Nearby Brightenings

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuhong; Zhang, Jun; Hou, Yijun; Li, Xiaohong [CAS Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Erdélyi, Robertus [Solar Physics and Space Plasma Research Centre, School of Mathematics and Statistics, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom); Yan, Limei, E-mail: shuhongyang@nao.cas.cn [Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029 (China)

    2017-07-01

    Light walls, as ensembles of oscillating bright structures rooted in sunspot light bridges, have not been well studied, although they are important for understanding sunspot properties. Using the Interface Region Imaging Spectrograph and Solar Dynamics Observatory observations, here we study the evolution of two oscillating light walls each within its own active region (AR). The emission of each light wall decays greatly after the appearance of adjacent brightenings. For the first light wall, rooted within AR 12565, the average height, amplitude, and oscillation period significantly decrease from 3.5 Mm, 1.7 Mm, and 8.5 minutes to 1.6 Mm, 0.4 Mm, and 3.0 minutes, respectively. For the second light wall, rooted within AR 12597, the mean height, amplitude, and oscillation period of the light wall decrease from 2.1 Mm, 0.5 Mm, and 3.0 minutes to 1.5 Mm, 0.2 Mm, and 2.1 minutes, respectively. Particularly, a part of the second light wall even becomes invisible after the influence of a nearby brightening. These results reveal that the light walls are suppressed by nearby brightenings. Considering the complex magnetic topology in light bridges, we conjecture that the fading of light walls may be caused by a drop in the magnetic pressure, where the flux is canceled by magnetic reconnection at the site of the nearby brightening. Another hypothesis is that the wall fading is due to the suppression of driver source ( p -mode oscillation), resulting from the nearby avalanche of downward particles along reconnected brightening loops.

  15. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding...... the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary...

  16. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates temporal suppression of click-evoked otoacoustic emissions (CEOAEs), occurring when a suppressor-click is presented close in time to a test-click (e.g. 0-8ms). Various temporal suppression methods for examining temporal changes in cochlear compression were evaluated and me...... under test. Temporal suppression was shown to be comparable for CEOAEs and SSOAEs, indicating similar underlying cochlear nonlinear mechanisms. This study contributes to a better understanding of the temporal properties of cochlear dynamics....

  17. Social Hierarchy and Depression: The Role of Emotion Suppression

    OpenAIRE

    Langner, Carrie A.; Epel, Elissa; Matthews, Karen; Moskowitz, Judith T.; Adler, Nancy

    2012-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depre...

  18. Psychophysical research progress of interocular suppression in amblyopic visual system

    OpenAIRE

    Jing-Jing Li; Yi Huang

    2016-01-01

    Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement an...

  19. Binocular vision in amblyopia : structure, suppression and plasticity

    OpenAIRE

    Hess, Robert F; Thompson, Benjamin; Baker, Daniel Hart

    2014-01-01

    The amblyopic visual system was once considered to be structurally monocular. However, it now evident that the capacity for binocular vision is present in many observers with amblyopia. This has led to new techniques for quantifying suppression that have provided insights into the relationship between suppression and the monocular and binocular visual deficits experienced by amblyopes. Furthermore, new treatments are emerging that directly target suppressive interactions within the visual cor...

  20. Precipitates/Salts Model Sensitivity Calculation

    International Nuclear Information System (INIS)

    Mariner, P.

    2001-01-01

    The objective and scope of this calculation is to assist Performance Assessment Operations and the Engineered Barrier System (EBS) Department in modeling the geochemical effects of evaporation on potential seepage waters within a potential repository drift. This work is developed and documented using procedure AP-3.12Q, ''Calculations'', in support of ''Technical Work Plan For Engineered Barrier System Department Modeling and Testing FY 02 Work Activities'' (BSC 2001a). The specific objective of this calculation is to examine the sensitivity and uncertainties of the Precipitates/Salts model. The Precipitates/Salts model is documented in an Analysis/Model Report (AMR), ''In-Drift Precipitates/Salts Analysis'' (BSC 2001b). The calculation in the current document examines the effects of starting water composition, mineral suppressions, and the fugacity of carbon dioxide (CO 2 ) on the chemical evolution of water in the drift

  1. Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Blokhuis, Gijsbert J.; Diender, Marije G.; Oyen, Wim J.G. [Radboud University Medical Center, Department of Nuclear Medicine, Nijmegen (Netherlands); Bleeker-Rovers, Chantal P. [Radboud University Medical Center, Division of Infectious Diseases, Department of Internal Medicine, Nijmegen (Netherlands); Draaisma, Jos M.T. [Radboud University Medical Center, Department of Paediatrics, Nijmegen (Netherlands); Geus-Oei, Lioe-Fee de [Radboud University Medical Center, Department of Nuclear Medicine, Nijmegen (Netherlands); University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, Biomedical Photonic Imaging Group, Enschede (Netherlands)

    2014-10-15

    Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression. All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis. FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively. FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value. (orig.)

  2. Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

    International Nuclear Information System (INIS)

    Blokhuis, Gijsbert J.; Diender, Marije G.; Oyen, Wim J.G.; Bleeker-Rovers, Chantal P.; Draaisma, Jos M.T.; Geus-Oei, Lioe-Fee de

    2014-01-01

    Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression. All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis. FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively. FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value. (orig.)

  3. Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

    Science.gov (United States)

    La Cesa, S; Di Stefano, G; Leone, C; Pepe, A; Galosi, E; Alu, F; Fasolino, A; Cruccu, G; Valeriani, M; Truini, A

    2018-01-01

    In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system. © 2017 European Pain Federation - EFIC®.

  4. Screening sensitivity theory

    International Nuclear Information System (INIS)

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  5. Highly Sensitive Optical Receivers

    CERN Document Server

    Schneider, Kerstin

    2006-01-01

    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  6. Long-Term Sensitization Training in "Aplysia" Decreases the Excitability of a Decision-Making Neuron through a Sodium-Dependent Mechanism

    Science.gov (United States)

    Hernandez, John S.; Wainwright, Marcy L.; Mozzachiodi, Riccardo

    2017-01-01

    In "Aplysia," long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na[superscript +] and K[superscript +] channels to B51 decreased…

  7. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs...... suppression is present in all CEOAEs for inter-click intervals (ICIs) less than 8 ms. The long-latency CEOAEs showed augmentation (i.e., negative suppression) for ICIs of 6-7 ms which was not reported for the short-latency CEOAE at these ICIs. A phenomenological approach is adopted here to explain both...

  8. Electronic Warfare: Comprehensive Strategy Needed for Suppressing Enemy Air Defenses

    National Research Council Canada - National Science Library

    2001-01-01

    .... To achieve this suppression, the services use specialized aircraft designed to neutralize, destroy, or temporarily degrade enemy air defense systems through either physical attack or electronic warfare...

  9. Disease Suppressive Soils: New Insights from the Soil Microbiome.

    Science.gov (United States)

    Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

    2017-11-01

    Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

  10. Double suppression of FCNCs in a supersymmetric model

    International Nuclear Information System (INIS)

    Kajiyama, Yuji

    2004-01-01

    A concrete model which can suppress FCNCs and CP violating phenomena is suggested. It is S 3 symmetric extension of MSSM in extra dimensions where only SU(2) and SU(3) gauge multiplet are assumed to propagate in the bulk. They are suppressed due to S 3 flavor symmetry at M SUSY , and the infrared attractive force of gauge interaction in extra dimensions are used to suppress them at the compactification scale. We find that O(1) disorders of the soft parameters are allowed at the cut-off scale to suppress FCNCs and CP violating phenomena. (author)

  11. Double suppression of FCNCs in a supersymmetric model

    Energy Technology Data Exchange (ETDEWEB)

    Kajiyama, Yuji [Kanazawa Univ., Dept. of Physics, Kanazawa, Ishikawa (Japan)

    2004-12-01

    A concrete model which can suppress FCNCs and CP violating phenomena is suggested. It is S{sub 3} symmetric extension of MSSM in extra dimensions where only SU(2) and SU(3) gauge multiplet are assumed to propagate in the bulk. They are suppressed due to S{sub 3} flavor symmetry at M{sub SUSY}, and the infrared attractive force of gauge interaction in extra dimensions are used to suppress them at the compactification scale. We find that O(1) disorders of the soft parameters are allowed at the cut-off scale to suppress FCNCs and CP violating phenomena. (author)

  12. The regional extent of suppression: strabismics versus nonstrabismics.

    Science.gov (United States)

    Babu, Raiju Jacob; Clavagnier, Simon R; Bobier, William; Thompson, Benjamin; Hess, Robert F

    2013-10-09

    Evidence is accumulating that suppression may be the cause of amblyopia rather than a secondary consequence of mismatched retinal images. For example, treatment interventions that target suppression may lead to better binocular and monocular outcomes. Furthermore, it has recently been demonstrated that the measurement of suppression may have prognostic value for patching therapy. For these reasons, the measurement of suppression in the clinic needs to be improved beyond the methods that are currently available, which provide a binary outcome. We describe a novel quantitative method for measuring the regional extent of suppression that is suitable for clinical use. The method involves a dichoptic perceptual matching procedure at multiple visual field locations. We compare a group of normal controls (mean age: 28 ± 5 years); a group with strabismic amblyopia (four with microesotropia, five with esotropia, and one with exotropia; mean age: 35 ± 10 years); and a group with nonstrabismic anisometropic amblyopia (mean age: 33 ± 12 years). The extent and magnitude of suppression was similar for observers with strabismic and nonstrabismic amblyopia. Suppression was strongest within the central field and extended throughout the 20° field that we measured. Suppression extends throughout the central visual field in both strabismic and anisometropic forms of amblyopia. The strongest suppression occurs within the region of the visual field corresponding to the fovea of the fixing eye.

  13. Genetics Home Reference: warfarin sensitivity

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Warfarin sensitivity Warfarin sensitivity Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Warfarin sensitivity is a condition in which individuals have ...

  14. Study of rare and suppressed processes in B meson decays with ATLAS

    CERN Document Server

    Nikolaenko, V I; The ATLAS collaboration

    2014-01-01

    The large amount of Heavy Flavor data collected by the ATLAS experiment is potentially sensitive to New Physics, which could be evident in processes that are naturally suppressed in the Standard Model. The most recent results on the search for the rare decay Bs (B0) -> mu+mu- are presented. Recent results are also presented on the angular distribution parameters AFB and FL describing the decay Bd -> K*mu+mu- -> K+pi-mu+mu-. The accuracy obtained from data collected in 2011 is comparable to the best previous measurement in the region q^2(mu+mu-)>16 GeV^2.

  15. Study of rare and suppressed processes in B meson decays with ATLAS

    CERN Document Server

    Nikolaenko, V; The ATLAS collaboration

    2014-01-01

    The large amount of Heavy Flavor data collected by the ATLAS experiment is potentially sensitive to New Physics, which could be evident in processes that are naturally suppressed in the Standard Model. The most recent result on the search for the rare decay Bs (B0) -> mu+mu- is presented. Recent results are also presented on the angular distribution parameters AFB and FL describing the decay Bd -> K*mu+mu- -> K+pi-mu+mu-. The accuracy obtained from data collected in 2011 is comparable to the best previous measurement in the region q^2(mu+mu-)>16 GeV^2.

  16. Study of rare and suppressed processes in B meson decays with the ATLAS experiment

    CERN Document Server

    Iengo, P; The ATLAS collaboration

    2014-01-01

    The large amount of Heavy Flavor data collected by the ATLAS experiment is potentially sensitive to New Physics, which could be evident in processes that are naturally suppressed in the Standard Model. The most recent results on the search for the rare decay Bs (B0) -> mu+mu- are presented, as well as results of the angular analysis of the semileptonic rare decay Bd → K*0 mu+mu- -> K+pi-mu+mu-, extracting the distribution parameter AFB and FL (the accuracy obtained from data collected in 2011 is comparable to the best previous measurement in the region q^2(mu+mu-) -> 16 GeV^2)

  17. Coherent triplet excitation suppresses the heading error of the avian compass

    Energy Technology Data Exchange (ETDEWEB)

    Katsoprinakis, G E; Dellis, A T; Kominis, I K, E-mail: ikominis@iesl.forth.g [Department of Physics, University of Crete, Heraklion 71103 (Greece); Institute of Electronic Structure and Laser, Foundation for Research and Technology, Heraklion 71110 (Greece)

    2010-08-15

    Radical-ion pair reactions are currently understood to underlie the biochemical magnetic compass of migratory birds. It was recently shown that radical-ion pair reactions form a rich playground for the application of quantum-information-science concepts and effects. We will show here that the intricate interplay between the quantum Zeno effect and the coherent excitation of radical-ion pairs leads to an exquisite angular sensitivity of the reaction yields. This results in a significant and previously unanticipated suppression of the avian compass heading error, opening the way to quantum engineering precision biological sensors.

  18. PAYMENT CAPACITY SENSITIVITY FACTORS

    Directory of Open Access Journals (Sweden)

    Daniel BRÎNDESCU – OLARIU

    2014-11-01

    The results of the study facilitate the determination and classification of the main sensitivity factors for the payment capacity at sample level, the establishment of general benchmarks for the payment capacity (as no such benchmarks currently exist in the Romanian literature and the identification of the mechanisms through which the variation of different factors impacts the payment capacity.

  19. High-Sensitivity Spectrophotometry.

    Science.gov (United States)

    Harris, T. D.

    1982-01-01

    Selected high-sensitivity spectrophotometric methods are examined, and comparisons are made of their relative strengths and weaknesses and the circumstances for which each can best be applied. Methods include long path cells, noise reduction, laser intracavity absorption, thermocouple calorimetry, photoacoustic methods, and thermo-optical methods.…

  20. Sensitization of Parker fittings

    International Nuclear Information System (INIS)

    Wilber, W.W.

    1985-09-01

    At your request, ferrules from 316 SS Parker-Hannifen compression fittings at the FFTF have been examined and evaluated to determine the metallurgical condition as related to carbide precipitation in grain boundaries (known as sensitization) and the implications this may have with regard to corrosion resistance. To accomplish this, two ferrules from new stock, two ferrules from old stock and two ferrules that had seen service were examined metallurgically. The samples were prepared for optical metallography. They were viewed in both the etched and unetched condition and analyzed on the scanning electron microscope (SEM) for elemental content. It was confirmed that the ferrules from new stock had a 5 mil thick nitrided layer on the ferrule ID at the lead end and that the 316 SS ferrule material was in the sensitized condition, indicating low resistance to aqueous corrosion. The material from old stock had no nitride layer but was in the sensitized condition indicating low resistance to aqueous corrosion. The ferrules that had seen service had not been nitrided and were not sensitized indicating high resistance to aqueous corrosion

  1. Radiation-sensitive diacrylates

    International Nuclear Information System (INIS)

    Demajistre, R.

    1976-01-01

    Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysts to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials. 6 claims, no drawings

  2. Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Junge, Anne Gram

    Et voksende antal mennesker i Danmark oplever at være overfølsomme over for dufte og kemikalier. Imidlertid er den tilskrevne diagnose Multiple Chemical Sensitivity (MCS) ikke medicinsk anerkendt i Danmark pga. mangel på organiske og patofysiologisk basis for symptomerne. Dette speciale bygger på...

  3. Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus.

    Science.gov (United States)

    Tsaltas, E; Schugens, M M; Gray, J A

    1989-01-01

    The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning.

  4. Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis

    DEFF Research Database (Denmark)

    Melief, Jeroen; Koper, Jan W; Endert, Erik

    2016-01-01

    As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA...

  5. Suppressing images of desire: Neural correlates of chocolate-related thoughts in high and low trait chocolate cravers.

    Science.gov (United States)

    Miedl, Stephan F; Blechert, Jens; Meule, Adrian; Richard, Anna; Wilhelm, Frank H

    2018-03-05

    Chocolate is the most often craved food in Western societies and many individuals try to resist its temptation due to weight concerns. Suppressing chocolate-related thoughts might, however, lead to paradoxical enhancements of these thoughts and this effect might be more pronounced in individuals with frequent chocolate cravings. In the current study, neural and cognitive correlates of chocolate thought suppression were investigated as a function of trait chocolate craving. Specifically, 20 high and 20 low trait chocolate cravers followed suppression vs. free thinking instructions after being exposed to chocolate and neutral images. Enhanced cue reactivity was evident in high trait chocolate cravers in that they reported more chocolate-related thoughts selectively after chocolate images compared to their low trait craving counterparts. This cue reactivity was mirrored neurally by higher activation in the ventral and dorsal striatum, demonstrating enhanced reward system activity. Unexpectedly, high trait chocolate cravers successfully reduced their elevated chocolate thoughts in the suppression condition. This lends support for the use of thought suppression as a means of regulating unwanted thoughts, cravings and imagery. Whether this thought manipulation is able to curb the elevated cue reactivity and the underlying reward sensitivity in chocolate cravers in applied settings remains to be shown. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R.; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E.; Tyner, Jeffrey W.; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo

    2012-01-01

    Fanconi anemia, complementation group C (FANCC)–deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist–stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)–deficient macrophages containing an NF-κB/AP-1–responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK–dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation. PMID:22234699

  7. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E; Tyner, Jeffrey W; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo; Bagby, Grover C

    2012-03-01

    Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist-stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)-deficient macrophages containing an NF-κB/AP-1-responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK-dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation.

  8. Suppression of Protonated Organic Solvents in NMR Spectroscopy Using a Perfect Echo Low-Pass Filtration Pulse Sequence.

    Science.gov (United States)

    Howe, Peter W A

    2018-04-03

    Proton NMR spectra are usually acquired using deuterated solvents, but in many cases it is necessary to obtain spectra on samples in protonated solvents. In these cases, the intense resonances of the protonated solvents need to be suppressed to maximize sensitivity and spectral quality. A wide range of highly effective solvent suppression methods have been developed, but additional measures are needed to suppress the 13 C satellites of the solvent. Because the satellites represent 1.1% of the original solvent signal, they remain problematic if unsuppressed. The recently proposed DISPEL pulse sequences suppress 13 C satellites extremely effectively, and this Technical Note demonstrates that combining DISPEL and presaturation results in exceptionally effective solvent suppression. An important element in the effectiveness is volume selection, which is inherent within the DISPEL sequence. Spectra acquired in protonated dimethlysulfoxide and tetrahydrofuran show that optimum results are obtained by modifying the phase cycle, cycling the pulse-field gradients, and using broadband 13 C inversion pulses to reduce the effects of radiofrequency offset and inhomogeneity.

  9. Suppress to feel and remember less: Neural correlates of explicit and implicit emotional suppression on perception and memory.

    Science.gov (United States)

    Katsumi, Yuta; Dolcos, Sanda

    2018-02-09

    Available evidence suggests that emotion regulation can modulate both immediate (emotional experience) and long-term (episodic memory) effects of emotion, and that both explicit and implicit forms may be effective. However, neural mechanisms by which explicit and implicit emotional suppression affect these phenomena remain unclear, particularly regarding their effects on memory. In this study, participants rated the emotional content of negative and neutral images, following explicit (verbal instructions) or implicit (priming) induction of emotional suppression goals, during functional magnetic resonance imaging. Participants' memory for the images was tested one week later. Behaviorally, explicit suppression reduced emotional ratings of negative images, whereas both explicit and implicit suppression reduced subsequent memory. At the neural level, the engagement of explicit suppression was uniquely associated with decreased activity in the amygdala (AMY), during emotional ratings, and in the AMY and inferior frontal gyrus (IFG), during successful encoding. Although both explicit and implicit suppression diminished functional connectivity between these regions and the hippocampus (HC) linked to successful encoding, explicit suppression was uniquely associated with interference with AMY-HC interactions, which no longer predicted subsequent memory for the explicitly-suppressed items. Overall, these findings advance our understanding of the common and dissociable mechanisms of explicit and implicit emotional suppression on perception and memory, and suggest their impact on both bottom-up and top-down mechanisms involved in emotion-cognition interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. The effect of mindfulness meditation on cough reflex sensitivity.

    Science.gov (United States)

    Young, E C; Brammer, C; Owen, E; Brown, N; Lowe, J; Johnson, C; Calam, R; Jones, S; Woodcock, A; Smith, J A

    2009-11-01

    Chronic cough is common, and medical treatment can be ineffective. Mindfulness is a psychological intervention that aims to teach moment-to-moment non-judgemental awareness of thoughts, feelings and sensations. 30 healthy subjects and 30 patients with chronic cough were studied in two sequential trials. For both studies, cough reflex sensitivity to citric acid (C5) was measured on two occasions, with urge to cough rated following each inhalation; between challenges subjects were randomised to (1) no intervention, (2) mindfulness or (3) no intervention but modified cough challenge (subjects suppress coughing). For the healthy volunteers, measures were 1 h apart and mindfulness was practised for 15 min. For the patients with chronic cough measures were 1 week apart and mindfulness was practised daily for 30 min. In healthy volunteers, median change (interquartile range (IQR)) in cough reflex sensitivity (logC5) for no intervention, mindfulness and suppression was +1.0 (0.0 to +1.3), +2.0 (+1.0 to +3.0) and +3.0 (+2.8 to +3.0) doubling concentrations (p = 0.003); there were significant reductions for both mindfulness (p = 0.043) and suppression (p = 0.002) over no intervention. In patients with cough, median change (IQR) in logC5 for no intervention, mindfulness training and voluntary suppression was 0.0 (-1.0 to +1.0), +1.0 (-0.3 to +1.0) and +1.0 (+1.0 to +2.0) doubling concentrations (p = 0.046); there was a significant reduction for suppression (p = 0.02) but not mindfulness (p = 0.35). Urge to cough did not change after mindfulness compared with control in either healthy subjects (p = 0.33) or those with chronic cough (p = 0.47). Compared with control, mindfulness decreased cough reflex sensitivity in healthy volunteers, but did not alter cough threshold in patients with chronic cough. Both groups were able to suppress cough responses to citric acid inhalation.

  11. High rate of virological re-suppression among patients failing ...

    African Journals Online (AJOL)

    Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the ...

  12. Thought Suppression and Meaning in Life: A Longitudinal Investigation

    Science.gov (United States)

    Krause, Neal

    2007-01-01

    The purpose of this study is to see if older adults who experience problems with thought suppression tend to encounter greater difficulty deriving a sense of meaning in life. Data from a longitudinal nationwide survey of older people (N = 988) indicate that greater difficulty with thought suppression is associated with a decline in meaning over…

  13. Dynamic interactions of the cortical networks during thought suppression.

    Science.gov (United States)

    Aso, Toshihiko; Nishimura, Kazuo; Kiyonaka, Takashi; Aoki, Takaaki; Inagawa, Michiyo; Matsuhashi, Masao; Tobinaga, Yoshikazu; Fukuyama, Hidenao

    2016-08-01

    Thought suppression has spurred extensive research in clinical and preclinical fields, particularly with regard to the paradoxical aspects of this behavior. However, the involvement of the brain's inhibitory system in the dynamics underlying the continuous effort to suppress thoughts has yet to be clarified. This study aims to provide a unified perspective for the volitional suppression of internal events incorporating the current understanding of the brain's inhibitory system. Twenty healthy volunteers underwent functional magnetic resonance imaging while they performed thought suppression blocks alternating with visual imagery blocks. The whole dataset was decomposed by group-independent component analysis into 30 components. After discarding noise components, the 20 valid components were subjected to further analysis of their temporal properties including task-relatedness and between-component residual correlation. Combining a long task period and a data-driven approach, we observed a right-side-dominant, lateral frontoparietal network to be strongly suppression related. This network exhibited increased fluctuation during suppression, which is compatible with the well-known difficulty of suppression maintenance. Between-network correlation provided further insight into the coordinated engagement of the executive control and dorsal attention networks, as well as the reciprocal activation of imagery-related components, thus revealing neural substrates associated with the rivalry between intrusive thoughts and the suppression process.

  14. Suppressive mechanisms in visual motion processing: From perception to intelligence.

    Science.gov (United States)

    Tadin, Duje

    2015-10-01

    Perception operates on an immense amount of incoming information that greatly exceeds the brain's processing capacity. Because of this fundamental limitation, the ability to suppress irrelevant information is a key determinant of perceptual efficiency. Here, I will review a series of studies investigating suppressive mechanisms in visual motion processing, namely perceptual suppression of large, background-like motions. These spatial suppression mechanisms are adaptive, operating only when sensory inputs are sufficiently robust to guarantee visibility. Converging correlational and causal evidence links these behavioral results with inhibitory center-surround mechanisms, namely those in cortical area MT. Spatial suppression is abnormally weak in several special populations, including the elderly and individuals with schizophrenia-a deficit that is evidenced by better-than-normal direction discriminations of large moving stimuli. Theoretical work shows that this abnormal weakening of spatial suppression should result in motion segregation deficits, but direct behavioral support of this hypothesis is lacking. Finally, I will argue that the ability to suppress information is a fundamental neural process that applies not only to perception but also to cognition in general. Supporting this argument, I will discuss recent research that shows individual differences in spatial suppression of motion signals strongly predict individual variations in IQ scores. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Burst-Suppression Ratio on Electrocorticography Depends on Interelectrode Distance

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Calin, Alexandru; Kumaraswamy, Vishakhadatta M.

    2016-01-01

    Introduction: With deepening of anesthesia-induced comatose states, the EEG becomes fragmented by increasing periods of suppression. When measured from conventional EEG recordings, the binary burst-suppression signal (BS) appears similar across the scalp. As such, the BS ratio (BSR), quantifying...

  16. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    DEFF Research Database (Denmark)

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  17. Social hierarchy and depression: the role of emotion suppression.

    Science.gov (United States)

    Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

    2012-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

  18. Suppression of mouse-killing in rats following irradiation

    International Nuclear Information System (INIS)

    O'Boyle, M.

    1976-01-01

    Suppression of mouse-killing was produced following pairings of mouse-presentations (CS) with 96 roentgens of ionizing radiation (US) at 0 (less than 2 min.) and 30 min. US-CS interstimulus intervals. No suppression was found at CS-US intervals of 30 min., 1 hr., and 2 hr., or at US-CS intervals of 1 hr. and 2 hr

  19. How best to assess suppression in patients with high anisometropia.

    Science.gov (United States)

    Li, Jinrong; Hess, Robert F; Chan, Lily Y L; Deng, Daming; Chen, Xiang; Yu, Minbin; Thompson, Benjamin S

    2013-02-01

    We have recently described a rapid technique for measuring suppression using a dichoptic signal/noise task. Here, we report a modification of this technique that allows for accurate measurements to be made in amblyopic patients with high levels of anisometropia. This was necessary because aniseikonic image size differences between the two eyes can provide a cue for signal/noise segregation and, therefore, influence suppression measurement in these patients. Suppression was measured using our original technique and with a modified technique whereby the size of the signal and noise elements was randomized across the stimulus to eliminate size differences as a cue for task performance. Eleven patients with anisometropic amblyopia, five with more than 5 diopters (D) spherical equivalent difference (SED), six with less than 5 D SED between the eyes, and 10 control observers completed suppression measurements using both techniques. Suppression measurements in controls and patients with less than 5 D SED were constant across the two techniques; however, patients with more than 5 D SED showed significantly stronger suppression on the modified technique with randomized element size. Measurements made with the modified technique correlated with the loss of visual acuity in the amblyopic eye and were in good agreement with previous reports using detailed psychophysical measurements. The signal/noise technique for measuring suppression can be applied to patients with high levels of anisometropia and aniseikonia if element size is randomized. In addition, deeper suppression is associated with a greater loss of visual acuity in patients with anisometropic amblyopia.

  20. Improved fat suppression of the breast using discretized frequency shimming

    NARCIS (Netherlands)

    van der Velden, Tijl A.; Luijten, Peter R.; Klomp, DWJ

    2018-01-01

    Purpose: Robust fat suppression is essential in bilateral breast MRI at 7 Tesla. The lack of good fat suppression can result in errors when calculating the enhancement curve from dynamic contrast-enhanced acquisitions. In this work we propose discretized frequency shimming to improve the quality of

  1. Continuous Flash Suppression: Stimulus Fractionation rather than Integration.

    Science.gov (United States)

    Moors, Pieter; Hesselmann, Guido; Wagemans, Johan; van Ee, Raymond

    2017-10-01

    Recent studies using continuous flash suppression suggest that invisible stimuli are processed as integrated, semantic entities. We challenge the viability of this account, given recent findings on the neural basis of interocular suppression and replication failures of high-profile CFS studies. We conclude that CFS reveals stimulus fractionation in visual cortex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Eye Contact Facilitates Awareness of Faces during Interocular Suppression

    Science.gov (United States)

    Stein, Timo; Senju, Atsushi; Peelen, Marius V.; Sterzer, Philipp

    2011-01-01

    Eye contact captures attention and receives prioritized visual processing. Here we asked whether eye contact might be processed outside conscious awareness. Faces with direct and averted gaze were rendered invisible using interocular suppression. In two experiments we found that faces with direct gaze overcame such suppression more rapidly than…

  3. Nature of dynamical suppressions in the generalized Veneziano model

    International Nuclear Information System (INIS)

    Odorico, R.

    1976-05-01

    It is shown by explicit numerical calculations that of a class of coupling suppressions existing in the generalized Veneziano model, which have been recently used to interpret the psi data and other related phenomena, only a part can be attributed to the exponential growth with energy of the number of levels in the model. The remaining suppressions have a more direct dual origin

  4. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40, Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayoshi [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

    2013-02-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.

  5. Bandwidth-limited control and ringdown suppression in high-Q resonators.

    Science.gov (United States)

    Borneman, Troy W; Cory, David G

    2012-12-01

    We describe how the transient behavior of a tuned and matched resonator circuit and a ringdown suppression pulse may be integrated into an optimal control theory (OCT) pulse-design algorithm to derive control sequences with limited ringdown that perform a desired quantum operation in the presence of resonator distortions of the ideal waveform. Inclusion of ringdown suppression in numerical pulse optimizations significantly reduces spectrometer deadtime when using high quality factor (high-Q) resonators, leading to increased signal-to-noise ratio (SNR) and sensitivity of inductive measurements. To demonstrate the method, we experimentally measure the free-induction decay of an inhomogeneously broadened solid-state free radical spin system at high Q. The measurement is enabled by using a numerically optimized bandwidth-limited OCT pulse, including ringdown suppression, robust to variations in static and microwave field strengths. We also discuss the applications of pulse design in high-Q resonators to universal control of anisotropic-hyperfine coupled electron-nuclear spin systems via electron-only modulation even when the bandwidth of the resonator is significantly smaller than the hyperfine coupling strength. These results demonstrate how limitations imposed by linear response theory may be vastly exceeded when using a sufficiently accurate system model to optimize pulses of high complexity. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayoshi; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

    2013-01-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion

  7. Open and closed heavy-flavour suppression in heavy-ion collisions with CMS

    CERN Document Server

    Jo, Mihee

    2014-01-01

    The Compact Muon Solenoid (CMS) is fully equipped to measure quarkonia in the di-muon decay channel in the high multiplicity environment of nucleus-nucleus collisions. Quarkonia are especially relevant for studying the quark-gluon plasma since they are produced at early times and propagate through the medium, mapping its evolution. CMS has measured the nuclear modification factors of non-prompt $J/\\psi$ (from b-hadron decays), prompt $J/\\psi$, inclusive $\\psi$(2S), and the first three $Y$ states in PbPb collisions at $\\sqrt{s_{NN}}$ = 2.76 TeV. A suppression of non-prompt $J/\\psi$, which is sensitive to the in-medium b-quark energy loss, has been measured at relatively high $p_{T}$ $(6.5 < p_{T} < 30 GeV/c)$ in PbPb collisions, compared to the yield in pp collisions scaled by the number of inelastic nucleon-nucleon collisions. For prompt $J/\\psi$ in the same kinematic range, a strong, centrality-dependent suppression is observed. Such strong suppression at high $p_{T}$ has previously not been observed a...

  8. Volcanic suppression of Nile summer flooding triggers revolt and constrains interstate conflict in ancient Egypt.

    Science.gov (United States)

    Manning, Joseph G; Ludlow, Francis; Stine, Alexander R; Boos, William R; Sigl, Michael; Marlon, Jennifer R

    2017-10-17

    Volcanic eruptions provide tests of human and natural system sensitivity to abrupt shocks because their repeated occurrence allows the identification of systematic relationships in the presence of random variability. Here we show a suppression of Nile summer flooding via the radiative and dynamical impacts of explosive volcanism on the African monsoon, using climate model output, ice-core-based volcanic forcing data, Nilometer measurements, and ancient Egyptian writings. We then examine the response of Ptolemaic Egypt (305-30 BCE), one of the best-documented ancient superpowers, to volcanically induced Nile suppression. Eruptions are associated with revolt onset against elite rule, and the cessation of Ptolemaic state warfare with their great rival, the Seleukid Empire. Eruptions are also followed by socioeconomic stress with increased hereditary land sales, and the issuance of priestly decrees to reinforce elite authority. Ptolemaic vulnerability to volcanic eruptions offers a caution for all monsoon-dependent agricultural regions, presently including 70% of world population.The degree to which human societies have responded to past climatic changes remains unclear. Here, using a novel combination of approaches, the authors show how volcanically-induced suppression of Nile summer flooding led to societal unrest in Ptolemaic Egypt (305-30 BCE).

  9. Selective suppression of antibody production with the aid of radiolabelled birch pollen allergen

    International Nuclear Information System (INIS)

    Filipp, G.; Biro, G.; Hartung, W.D.; Lehmann, G.

    1981-01-01

    In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of of the radiolabelled pollen allergen (75-1000 μCi 125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, in accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of a subsequent intravenously administered radiolabelled birch pollen allergen (750-1000μCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected. (author)

  10. Effect of low dose x-irradiation on alloantigen sensitized and unsensitized lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Dohi, Kiyohiko; Yahata, Hiroshi; Fukuda, Yasuhiko; Asahara, Toshimasa; Ono, Eiji; Ezaki, Haruo

    1984-12-01

    The effect of local graft irradiation on immune response in allograft in which acute rejection occurs was studied using an in vitro model. Unidirectional mixed lymphocyte culture (MLC) was used as the in vitro model of acute rejection. 150 and 300 rad x-irradiation suppressed mixed lymphocyte reaction (MLR) but did not cell-mediated-lympholysis (CML) of unsensitized lymphocytes. X-irradiated alloantigen sensitized cells (ASC) generated in 6-day MLC suppressed MLR and CML of unsensitized lymphocytes. Suppressive effects of x-irradiated ASC were of the same degree by x-irradiation doses of 150-500 rad. Suppressive effect of x-irradiation was maintained for only a short period after x-irradiation. Potential function of suppressor precursor cells among unsensitized lymphocytes was abolished by x-irradiation of 300 rad. (author).

  11. A dual purpose Compton suppression spectrometer

    CERN Document Server

    Parus, J; Raab, W; Donohue, D

    2003-01-01

    A gamma-ray spectrometer with a passive and an active shield is described. It consists of a HPGe coaxial detector of 42% efficiency and 4 NaI(Tl) detectors. The energy output pulses of the Ge detector are delivered into the 3 spectrometry chains giving the normal, anti- and coincidence spectra. From the spectra of a number of sup 1 sup 3 sup 7 Cs and sup 6 sup 0 Co sources a Compton suppression factor, SF and a Compton reduction factor, RF, as the parameters characterizing the system performance, were calculated as a function of energy and source activity and compared with those given in literature. The natural background is reduced about 8 times in the anticoincidence mode of operation, compared to the normal spectrum which results in decreasing the detection limits for non-coincident gamma-rays up to a factor of 3. In the presence of other gamma-ray activities, in the range from 5 to 11 kBq, non- and coincident, the detection limits can be decreased for some nuclides by a factor of 3 to 5.7.

  12. Is neutrinoless double beta decay suppressed

    International Nuclear Information System (INIS)

    Tomoda, T.

    1989-01-01

    Much effort has been devoted to the study of nuclear double beta decay, since the observation of a neutrinoless double beta (OνΒΒ) decay would be clear evidence that the electron neutrino is a Majorana particle. The OνΒΒ decay is caused by a finite Majorana neutrino mass and/or an admixture of right-handed leptonic currents. In order to relate these quantities to OνΒΒ decay rates, we need nuclear matrix elements, which are model dependent. One of the possibilities of testing nuclear models employed in such analysis is to calculate the experimentally known rates of ΒΒ decay with emission of two neutrinos (2νΒΒ decay) which occurs independently of the nature of the neutrino. There was a long-standing difficulty in such attempts that the calculated 2νΒΒ decay rates turned out to be always too large by one to two orders of magnitude. Trying to overcome such difficulty, Klapdor and Grotz as well as Vogel and Zirnbauer showed in their calculation using schematic effective interactions such that 2νΒΒ decay rates can get reduced considerably due to the nuclear ground state correlations. This paper reports that the suppression is ascribed to that of the virtual Gamow-Teller transitions from the excited 1 + states of the intermediate odd-odd -even nucleus

  13. Myeloma cells suppress osteoblasts through sclerostin secretion

    Energy Technology Data Exchange (ETDEWEB)

    Colucci, S; Brunetti, G; Oranger, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Mori, G [Department of Biomedical Science, University of Foggia, Foggia (Italy); Sardone, F [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Specchia, G; Rinaldi, E; Curci, P; Liso, V [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Passeri, G [Department of Internal Medicine and Biomedical Sciences, Center for Metabolic Bone Diseases, University of Parma, Parma (Italy); Zallone, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Rizzi, R [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Grano, M [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy)

    2011-06-01

    Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.

  14. Glutamine supplementation suppresses herpes simplex virus reactivation.

    Science.gov (United States)

    Wang, Kening; Hoshino, Yo; Dowdell, Kennichi; Bosch-Marce, Marta; Myers, Timothy G; Sarmiento, Mayra; Pesnicak, Lesley; Krause, Philip R; Cohen, Jeffrey I

    2017-06-30

    Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-γ-inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1-infected IFN-γ-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

  15. Installation for the suppression of sodium fires

    International Nuclear Information System (INIS)

    Newman, R.N.; Payne, J.F.B.; Lee, C.J.; Rowe, D.M.J.

    1979-01-01

    The basic operating principles are discussed of a passive baffle-catch tray fire suppression system for sodium fires. A new design is described incorporating increased compartmentalization of the collecting and drainage parts of the device. The burning and smoke generation rates from trays with varying aperture sizes were measured. From the experiments it was found that the burning rate and smoke generation rates could be related satisfactorily to the aperture areas. For the smallest aperture size ( 2 ) it was found that the smoke release was considerably less than that from a fire of the same area, because the smoke deposited on the underside of the baffle. A re-ignition problem was found, where pillars of sodium oxide (wicks) grow upward from the surface of the drained sodium and begin to burn when level with the baffle aperature. From a knowledge of the rate of growth of the wicks, trays may be made sufficiently deep to avoid the problem. Self acting valves were developed which allow the passage of sodium through the aperture and close when drainage is complete. These devices were shown to effect complete extinction of the drained sodium. Using the designs proposed it is possible to construct a system that will reduce the smoke emission from the drained sodium by a factor approaching 10 3 , without the use of valves, or with the self acting valves developed, reduce the emission from the drained sodium to approximately zero. (author)

  16. Rotator cuff injury: fat suppression MR image

    International Nuclear Information System (INIS)

    Won, Jong Yoon; Suh, Jin Suck; Park, Chang Yun; Lee, Yeon Hee; Kim, Yong Soo

    1994-01-01

    We performed the study prospectively to evaluate the advantage of fat suppression MR in the diagnosis of rotator cuff injury. Ten symptomatic patients were studied with both conventional T2WI and FST2WI using chemical shift technique. Each image was analyzed for the assessment of injuries, conspicuity of the lesion, the presence of effusion in subacromical bursae and joint space, and presence of humeral head injury. Arthroscopy was done in 4 patients following MRI. We could made presumptive diagnoses on FSMR as identical as on conventional MR in six cases(1 normal, 2 tendinitis, 2 partial thickness tear, 1 full thickness tear), two of them were confirmed by arthroscopic procedures. Two cases of partial thickness tear proved by arthroscopy were detected on FST2WI, whereas they were considered tendinitis on conventional T2WI. There were another 2 cases who showed tendinitis on FSMR, but normal on conventional T2WI. They, however, were not confirmed by either arthroscopy or surgical procedure. We found the FSMR were superior to conventional T2WI in the conspicuity of lesions and detection of joint effusion and abnormalities on the humeral head. We think FSMR of the shoulder could have significant diagnostic advantages over the conventional spin-echo MR imaging

  17. Probiotics-mediated suppression of cancer.

    Science.gov (United States)

    So, Stephanie S Y; Wan, Murphy L Y; El-Nezami, Hani

    2017-01-01

    Probiotics can be used as an adjuvant for cancer prevention or/and treatment through their abilities to modulate intestinal microbiota and host immune response. Although most of the recent reviews have focused on the potential role of probiotics against colon cancer, only few of them include the probiotic effect on extraintestinal cancers. The present review covers the most important findings from the literature published during the past 20 months (from January 2015 to August 2016) regarding the probiotics-mediated suppression of both gastrointestinal and extraintestinal cancers and the underlying mechanisms. A comprehensive literature search in Pubmed, Science direct and Google scholar databases was conducted to locate all relevant articles that investigated the effect of probiotics on prevention/treatment of both gastrointestinal and extraintestinal cancers. Different mechanisms for the beneficial effects of probiotics against cancer were also discussed, mainly via modulation of gut microbiota which thereby influences host metabolism and immunity. Despite laboratory-based studies having demonstrated encouraging outcomes that probiotics possess antitumor effects, the benefits should not be exaggerated before we get more results from human clinical trials. These are very important before the medical community can accept the use of probiotics as an alternative therapy for cancer control.

  18. Rotator cuff injury: fat suppression MR image

    Energy Technology Data Exchange (ETDEWEB)

    Won, Jong Yoon; Suh, Jin Suck; Park, Chang Yun; Lee, Yeon Hee [Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Soo [Inje University College of Medicine, Busan (Korea, Republic of)

    1994-04-15

    We performed the study prospectively to evaluate the advantage of fat suppression MR in the diagnosis of rotator cuff injury. Ten symptomatic patients were studied with both conventional T2WI and FST2WI using chemical shift technique. Each image was analyzed for the assessment of injuries, conspicuity of the lesion, the presence of effusion in subacromical bursae and joint space, and presence of humeral head injury. Arthroscopy was done in 4 patients following MRI. We could made presumptive diagnoses on FSMR as identical as on conventional MR in six cases(1 normal, 2 tendinitis, 2 partial thickness tear, 1 full thickness tear), two of them were confirmed by arthroscopic procedures. Two cases of partial thickness tear proved by arthroscopy were detected on FST2WI, whereas they were considered tendinitis on conventional T2WI. There were another 2 cases who showed tendinitis on FSMR, but normal on conventional T2WI. They, however, were not confirmed by either arthroscopy or surgical procedure. We found the FSMR were superior to conventional T2WI in the conspicuity of lesions and detection of joint effusion and abnormalities on the humeral head. We think FSMR of the shoulder could have significant diagnostic advantages over the conventional spin-echo MR imaging.

  19. Suppression of PTEN transcription by UVA

    Science.gov (United States)

    Zhao, Baozhong; Ming, Mei; He, Yu-Ying

    2012-01-01

    Although UVA has different physical and biological targets than UVB, the contribution of UVA to skin cancer susceptibility and its molecular basis remain largely unknown. Here we show that chronic UVA radiation suppresses PTEN expression at the mRNA level. Subchronic and acute UVA radiation also down-regulated PTEN in normal human epidermal keratinocytes, skin culture and mouse skin. At the molecular level, chronic UVA radiation decreased the transcriptional activity of the PTEN promoter in a methylation-independent manner, while it had no effect on the protein stability or mRNA stability of PTEN. In contrast, we found that UVA-induced activation of the Ras/ERK/AKT and NF-κB pathways plays an important role in UV-induced PTEN down-regulation. Inhibiting ERK or AKT increases PTEN expression. Our findings may provide unique insights into PTEN down-regulation as a critical component of UVA’s molecular impact during keratinocyte transformation. PMID:23129115

  20. Pressure suppression device for nuclear reactor building

    International Nuclear Information System (INIS)

    Ikegame, Noboru.

    1992-01-01

    In a nuclear reactor building, there are disposed cooling coils connected to an air supply duct at the outside of the building, an air supply blower, an air supply duct having the top end opened, an exhaustion duct having the top end opened and a bypassing pipeline interposed between the exhaustion duct and the air supply duct on the side of the inlet of the cooling coils. In the reactor building, when a radioactive material leakage accident should occur, an isolation valve is closed to isolate the building from the outside. Further, bypassing isolation valve is opened to form a closed cooling circuit by the cooling coils, the air supply blower and the air supply duct, the exhaustion duct and the bypassing pipeline in the reactor building. With such a constitution, since air as the atmosphere in the building is circulated through the closed cooling circuit and cooled by the cooling coils, the temperature is not elevated. Accordingly, since the pressure elevation of the atmosphere in the building is suppressed, the atmosphere containing radioactive materials do not flow out of the building. (I.N.)

  1. PAYMENT CAPACITY SENSITIVITY FACTORS

    OpenAIRE

    Daniel BRÎNDESCU – OLARIU

    2014-01-01

    The current study focuses on the sensitivity of the corporate payment capacity. Through the nature of the subject, the research is based on simulating variations of the forecasted cash-flows of the companies included in the sample. The study employs 391 forecasted yearly cash-flows statements collected from 50 companies from Timis County (Romania), as well as the detailed hypotheses of the forecasts. The results of the study facilitate the determination and classification of the main se...

  2. Mutagenic sensitivity to triticales

    International Nuclear Information System (INIS)

    Reddy, V.R.K.

    1993-01-01

    The effect of gamma rays, ethyl methane sulphonate and their combined treatments on germination, survival, seedling height and sterility were studied in one winter Triticale var. 6TA 87 and one sprig Triticale var. cinnamon. Based on LD 50 , degree of reduction in seedling height and increase in seed and pollen sterility, it was concluded that Triticale var. cinnamon is highly sensitive and mutable compared to Triticale 6TA 876. (author). 5 refs., 2 tabs

  3. Exploring genetic suppression interactions on a global scale.

    Science.gov (United States)

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C; Yamaguchi, Takafumi N; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire E; Cao, Jessica; Cote, Atina; Gebbia, Marinella; Horecka, Gene; Horecka, Ira; Kuzmin, Elena; Legro, Nicole; Liang, Wendy; van Lieshout, Natascha; McNee, Margaret; San Luis, Bryan-Joseph; Shaeri, Fatemeh; Shuteriqi, Ermira; Sun, Song; Yang, Lu; Youn, Ji-Young; Yuen, Michael; Costanzo, Michael; Gingras, Anne-Claude; Aloy, Patrick; Oostenbrink, Chris; Murray, Andrew; Graham, Todd R; Myers, Chad L; Andrews, Brenda J; Roth, Frederick P; Boone, Charles

    2016-11-04

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression. Copyright © 2016, American Association for the Advancement of Science.

  4. Differential and Synergistic Functionality of Acylsugars in Suppressing Oviposition by Insect Herbivores.

    Directory of Open Access Journals (Sweden)

    Brian M Leckie

    Full Text Available Acylsugars are secondary metabolites exuded from type IV glandular trichomes that provide broad-spectrum insect suppression for Solanum pennellii Correll, a wild relative of cultivated tomato. Acylsugars produced by different S. pennellii accessions vary by sugar moieties (glucose or sucrose and fatty acid side chains (lengths and branching patterns. Our objective was to determine which acylsugar compositions more effectively suppressed oviposition of the whitefly Bemisia tabaci (Gennadius (Middle East--Asia Minor 1 Group, tobacco thrips, Frankliniella fusca (Hinds, and western flower thrips, Frankliniella occidentalis (Pergande. We extracted and characterized acylsugars from four S. pennellii accessions with different compositions, as well as from an acylsugar-producing tomato breeding line. We also fractionated the acylsugars of one S. pennellii accession to examine the effects of its components. Effects of acylsugars on oviposition were evaluated by administering a range of doses to oviposition sites of adult whiteflies and thrips in non-choice and choice bioassays, respectively. The acylsugars from S. pennellii accessions and the tomato breeding line demonstrated differential functionality in their ability to alter the distribution of whitefly oviposition and suppress oviposition on acylsugar treated substrates. Tobacco thrips were sensitive to all compositions while western flower thrips and whiteflies were more sensitive to acylsugars from a subset of S. pennellii accessions. It follows that acylsugars could thus mediate plant-enemy interactions in such a way as to affect evolution of host specialization, resistance specificity, and potentially host differentiation or local adaptation. The acylsugars from S. pennellii LA1376 were separated by polarity into two fractions that differed sharply for their sugar moieties and fatty acid side chains. These fractions had different efficacies, with neither having activity approaching that of the

  5. Interference and Sensitivity Analysis.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J; Halloran, M Elizabeth

    2014-11-01

    Causal inference with interference is a rapidly growing area. The literature has begun to relax the "no-interference" assumption that the treatment received by one individual does not affect the outcomes of other individuals. In this paper we briefly review the literature on causal inference in the presence of interference when treatments have been randomized. We then consider settings in which causal effects in the presence of interference are not identified, either because randomization alone does not suffice for identification, or because treatment is not randomized and there may be unmeasured confounders of the treatment-outcome relationship. We develop sensitivity analysis techniques for these settings. We describe several sensitivity analysis techniques for the infectiousness effect which, in a vaccine trial, captures the effect of the vaccine of one person on protecting a second person from infection even if the first is infected. We also develop two sensitivity analysis techniques for causal effects in the presence of unmeasured confounding which generalize analogous techniques when interference is absent. These two techniques for unmeasured confounding are compared and contrasted.

  6. Tactual sensitivity in hypochondriasis.

    Science.gov (United States)

    Haenen, M A; Schmidi, A J; Schoenmakers, M; van den Hout, M A

    1997-01-01

    In his article on amplification, somatization and somatoform disorders Barsky [Psychosomatics 1992; 33:28-34] pointed out the importance of studying the perception and processing of somatic and visceral symptoms. Subsequently, it was demonstrated that hypochondriacal patients are not more accurately aware of cardiac activity than a group of non-hypochondriacal patients. Authors concluded that hypochondriacal somatic complaints do not result from an unusually fine discriminative ability to detect normal physiological sensations that non-hypochondriacal patients are unable to perceive. The aim of the present study was to investigate tactual sensitivity to non-painful stimuli in hypochondriacal patients and healthy subjects. Twenty-seven outpatients with DSM-III-R hypochondriasis and 27 healthy control subjects were compared. In all subjects the two-point discrimination threshold was measured, as well as subjective sensitivity to harmless bodily sensations as measured by the Somatosensory Amplification Scale. It was found that hypochondriacal patients reported more distress and discomfort with benign bodily sensations. The two-point discrimination threshold of hypochondriacal patients was not significantly lower in patients as compared to controls. Hypochondriacal subjects considered themselves more sensitive to benign bodily sensations without being better able to discriminate between two tactual bodily signals. These findings of the present study correspond quite closely to those reported earlier.

  7. [Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

    Science.gov (United States)

    Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

    2016-03-22

    To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

  8. Disgust and Suppression of the Visual Cortex: Lateralization Effects?

    Directory of Open Access Journals (Sweden)

    Moon Wilton

    2012-05-01

    Full Text Available Research has shown that unlike other threat emotions, disgust does not evoke a typical sympathetic fight or flight response. Rather, disgust induces a parasympathetic response. A recent EEG study has demonstrated that this inhibitory reaction is also present in neuronal systems. Disgust stimuli elicited diminished Visual Event Related Potential (VERP amplitude in comparison to neutral and fear stimuli at P1 in the posterior Oz electrode (Kruesmark and Li, 2011 J Neurosci 31 (9, 3429–3434. In order to investigate whether VERPs were sensitive to different domains of disgust, we presented participants with random sequence of neutral, sociomoral, mutilation, and contamination images derived from the IAPS database. EEG results indicated no significant effect at Oz contrary to prior research. The results did, however, demonstrate lateralization effects. Whilst no differences were found between the disgust conditions themselves, the left P1 potential for all the disgust conditions was significantly attenuated compared to neutral. Conversely, this effect did not occur in the right posterior electrodes. In a second study, we presented the different disgust images in blocks in order to investigate the role of anticipation. Again, the left sided P1 was attenuated compared to neutral; however, on the right, mutilation elicited significantly greater P1 amplitude than did all other conditions. The results suggest suppressed visual processing for disgust elicitors in the left posterior regions and heightened activity for mutilation stimuli in the right, when mutilation was expected. These results may reflect a lateralized approach-avoidance mechanism, which begins as early as 125 ms after stimulus onset.

  9. Ag induced suppression of irradiation response in YBCO/Ag composite thin films

    International Nuclear Information System (INIS)

    Behera, D.; Mohanty, T.; Mohanta, D.; Patnaik, K.; Mishra, N.C.; Senapati, L.; Kanjilal, D.; Mehta, G.K.; Pinto, R.

    1999-01-01

    Practical application of cuprate superconductors in radiation environment demands that these systems remain insensitive to the irradiation induced defects. The cuprate superconductors however are many orders of magnitude more sensitive than the conventional low T c superconductors. To suppress the irradiation sensitivity of cuprates we consider a crystal engineering approach where metal ions as Ag is made to occupy inter and intra-granular sites of YBa 2 Cu 3 O 7 thin films. We show that superconducting and normal state properties of YBCO/Ag composite thin films prepared by laser ablation remain unchanged under 140 MeV Si ion irradiation up to fluence of 8 x 10 14 ions/cm 2 . The inter- and intra-granular occupancy of Ag is shown to induce microstructural modifications and rigidity to the CuO chains respectively which in turn lead to the radiation insensitivity of the composite films. (author)

  10. Sensitivity analysis technique for application to deterministic models

    International Nuclear Information System (INIS)

    Ishigami, T.; Cazzoli, E.; Khatib-Rahbar, M.; Unwin, S.D.

    1987-01-01

    The characterization of sever accident source terms for light water reactors should include consideration of uncertainties. An important element of any uncertainty analysis is an evaluation of the sensitivity of the output probability distributions reflecting source term uncertainties to assumptions regarding the input probability distributions. Historically, response surface methods (RSMs) were developed to replace physical models using, for example, regression techniques, with simplified models for example, regression techniques, with simplified models for extensive calculations. The purpose of this paper is to present a new method for sensitivity analysis that does not utilize RSM, but instead relies directly on the results obtained from the original computer code calculations. The merits of this approach are demonstrated by application of the proposed method to the suppression pool aerosol removal code (SPARC), and the results are compared with those obtained by sensitivity analysis with (a) the code itself, (b) a regression model, and (c) Iman's method

  11. Kinematic sensitivity of robot manipulators

    Science.gov (United States)

    Vuskovic, Marko I.

    1989-01-01

    Kinematic sensitivity vectors and matrices for open-loop, n degrees-of-freedom manipulators are derived. First-order sensitivity vectors are defined as partial derivatives of the manipulator's position and orientation with respect to its geometrical parameters. The four-parameter kinematic model is considered, as well as the five-parameter model in case of nominally parallel joint axes. Sensitivity vectors are expressed in terms of coordinate axes of manipulator frames. Second-order sensitivity vectors, the partial derivatives of first-order sensitivity vectors, are also considered. It is shown that second-order sensitivity vectors can be expressed as vector products of the first-order sensitivity vectors.

  12. Sensitizing pigment in the fly

    International Nuclear Information System (INIS)

    Vogt, K.; Kirschfeld, K.

    1983-01-01

    The sensitizing pigment hypothesis for the high UV sensitivity in fly photoreceptors (R1-6) is further substantiated by measurements of the polarisation sensitivity in the UV. The quantum yield of the energy transfer from sensitizing pigment to rhodopsin was estimated by electrophysiological measurements of the UV sensitivity and the rhabdomeric absorptance (at 490 nm) in individual receptor cells. The transfer efficiency is >=0.75 in receptors with an absorptance in the rhabdomeres of 0.55-0.95. This result suggests that the sensitizing pigment is bound in some way to the rhodopsin. A ratio of two molecules of sensitizing pigment per one rhodopsin is proposed. (orig.)

  13. Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

    Directory of Open Access Journals (Sweden)

    Kelly Ben L

    2010-02-01

    Full Text Available Abstract Background Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen Leishmania has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of Leishmania-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease. Methods We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of Leishmania using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of Leishmania uptake on LPS-induced cytokine expression with uptake of inert latex beads. Results Whilst Leishmania uptake alone did not induce significant levels of any cytokine analysed in this study, Leishmania uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, L. amazonensis was generally more suppressive than L. major. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during Leishmania uptake, in a parasite-specific manner. Conclusions During uptake by macrophages, Leishmania evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, Leishmania suppresses certain proinflammatory cytokine responses in a parasite

  14. Artificial neural network for suppression of banding artifacts in balanced steady-state free precession MRI.

    Science.gov (United States)

    Kim, Ki Hwan; Park, Sung-Hong

    2017-04-01

    The balanced steady-state free precession (bSSFP) MR sequence is frequently used in clinics, but is sensitive to off-resonance effects, which can cause banding artifacts. Often multiple bSSFP datasets are acquired at different phase cycling (PC) angles and then combined in a special way for banding artifact suppression. Many strategies of combining the datasets have been suggested for banding artifact suppression, but there are still limitations in their performance, especially when the number of phase-cycled bSSFP datasets is small. The purpose of this study is to develop a learning-based model to combine the multiple phase-cycled bSSFP datasets for better banding artifact suppression. Multilayer perceptron (MLP) is a feedforward artificial neural network consisting of three layers of input, hidden, and output layers. MLP models were trained by input bSSFP datasets acquired from human brain and knee at 3T, which were separately performed for two and four PC angles. Banding-free bSSFP images were generated by maximum-intensity projection (MIP) of 8 or 12 phase-cycled datasets and were used as targets for training the output layer. The trained MLP models were applied to another brain and knee datasets acquired with different scan parameters and also to multiple phase-cycled bSSFP functional MRI datasets acquired on rat brain at 9.4T, in comparison with the conventional MIP method. Simulations were also performed to validate the MLP approach. Both the simulations and human experiments demonstrated that MLP suppressed banding artifacts significantly, superior to MIP in both banding artifact suppression and SNR efficiency. MLP demonstrated superior performance over MIP for the 9.4T fMRI data as well, which was not used for training the models, while visually preserving the fMRI maps very well. Artificial neural network is a promising technique for combining multiple phase-cycled bSSFP datasets for banding artifact suppression. Copyright © 2016 Elsevier Inc. All

  15. Phase sensitive multichannel OCT

    International Nuclear Information System (INIS)

    Trasischker, W.

    2015-01-01

    The main aim of this thesis was to develop and improve phase sensitive, multichannel methods for optical coherence tomography (OCT) using light in the 840 nm and 1040 nm regime. Conventional OCT provides purely structural information by illuminating the sample by one beam and recording the backscattered signal with one detection channel. Combination of this approach with a raster scan enables the acquisition of 2D and 3D structural information with a resolution in the micrometer regime. However, sometimes additional image contrast or information is desired. Amongst other approaches, this can be provided by a phase sensitive analysis of the interference pattern. Combining phase sensitivity with the illumination of the sample by more than one beam and/or by recording the data using more than one data acquisition channel allows for even more enhanced imaging. While phase sensitive OCT gives access to additional contrast and information, multichannel OCT can provide higher imaging speed, scan eld size and exible dierential measurements. Amongst the dierential, phase sensitive approaches, Doppler OCT (DOCT) and polarization sensitive OCT (PS-OCT) are two of the most promising OCT modalities. While the former targets information on the movement of backscattering particles, the latter measures alterations of the polarization state of the light induced by the sample. Both techniques provide additional image contrast and are, due to the non-invasive and fast character of OCT, well suited for in vivo imaging of the human eye. In the course of this thesis, two dierent multichannel, phase sensitive OCT systems will be presented. First, a D-OCT system with three dierent sampling beams is described. With a central wavelength of 840 nm these three beams are emitted by three individual laser sources. This eectively eliminates any cross talk and provides the full depth range for each channel. Furthermore, by illuminating the sample from three dierent directions, the absolute

  16. Decisions reduce sensitivity to subsequent information.

    Science.gov (United States)

    Bronfman, Zohar Z; Brezis, Noam; Moran, Rani; Tsetsos, Konstantinos; Donner, Tobias; Usher, Marius

    2015-07-07

    Behavioural studies over half a century indicate that making categorical choices alters beliefs about the state of the world. People seem biased to confirm previous choices, and to suppress contradicting information. These choice-dependent biases imply a fundamental bound of human rationality. However, it remains unclear whether these effects extend to lower level decisions, and only little is known about the computational mechanisms underlying them. Building on the framework of sequential-sampling models of decision-making, we developed novel psychophysical protocols that enable us to dissect quantitatively how choices affect the way decision-makers accumulate additional noisy evidence. We find robust choice-induced biases in the accumulation of abstract numerical (experiment 1) and low-level perceptual (experiment 2) evidence. These biases deteriorate estimations of the mean value of the numerical sequence (experiment 1) and reduce the likelihood to revise decisions (experiment 2). Computational modelling reveals that choices trigger a reduction of sensitivity to subsequent evidence via multiplicative gain modulation, rather than shifting the decision variable towards the chosen alternative in an additive fashion. Our results thus show that categorical choices alter the evidence accumulation mechanism itself, rather than just its outcome, rendering the decision-maker less sensitive to new information. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  17. Enduring neurobehavioral effects of early life trauma mediated through learning and corticosterone suppression

    Directory of Open Access Journals (Sweden)

    Stephanie Moriceau

    2009-09-01

    Full Text Available Early life trauma alters later life emotions, including fear. To better understand mediating mechanisms, we subjected pups to either predictable or unpredictable trauma, in the form of paired or unpaired odor-0.5mA shock conditioning which, during a sensitive period, produces an odor preference and no learning respectively. Fear conditioning and its neural correlates were then assessed after the sensitive period at postnatal day (PN13 or in adulthood, ages when amygdala-dependent fear occurs. Our results revealed that paired odor-shock conditioning starting during the sensitive period (PN8-12 blocked fear conditioning in older infants (PN13 and pups continued to express olfactory bulb-dependent odor preference learning. This PN13 fear learning inhibition was also associated with suppression of shock-induced corticosterone, although the age appropriate amygdala-dependent fear learning was reinstated with systemic corticosterone (3mg/kg during conditioning. On the other hand, sensitive period odor-shock conditioning did not prevent adult fear conditioning, although freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were attenuated compared to adult conditioning without infant conditioning. Normal levels of freezing, amygdala and hippocampal 2-DG uptake were induced with systemic corticosterone (5mg/kg during adult conditioning. These results suggest that the contingency of early life trauma mediates at least some effects of early life stress through learning and suppression of corticosterone levels. However, developmental differences between infants and adults are expressed with PN13 infants’ learning consistent with the original learned preference, while adult conditioning overrides the original learned preference with attenuated amygdala-dependent fear learning.

  18. Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs.

    Directory of Open Access Journals (Sweden)

    Steven Schalekamp

    Full Text Available Chest radiographs (CXR are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA.The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies. The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs and 132 normal cases (or lungs. For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100. The area under the receiver operating characteristics curve (AUC served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive.The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01. Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%.The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity.

  19. Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

    Science.gov (United States)

    Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

    2016-01-01

    This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  20. Functional clonal deletion versus active suppression in transplantation tolerance induced by total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Morecki, S.; Leshem, B.; Weigensberg, M.; Bar, S.; Slavin, S.

    1985-01-01

    Transplantation tolerance and stable chimerism were established in adult mice conditioned with a short course of total-lymphoid irradiation (TLI) followed by infusion of 30 X 10(6) allogeneic bone marrow cells. Spleen cells of tolerant mice could not exert a proliferative or cytotoxic response against host-type cells in vitro and were unable to induce graft-versus-host reaction in secondary host-type recipients. The degree of suppression assessed by coculturing tolerant splenocytes in vitro in the one-way mixed lymphocyte reaction was quite variable--and, in some cases, was not at all demonstrable, although tolerance was clearly maintained. Suppression, when apparent, could not be ascribed to T lymphocytes. Suppressor cells were found to bind soybean agglutinin and could be separated from the nonsuppressive cells by means of this lectin. Dissociation of the suppressive population (SBA+ cells) from that which is normally alloreactive (SBA- cells) resulted in a suppressor cell-depleted fraction that was still unable to respond to host-type cells but regained reactivity to unrelated cells. Limiting dilution analysis of chimeric splenocytes revealed markedly reduced frequencies of cytotoxic T lymphocyte precursors (CTL-P) directed against host-type cells, as compared with normal splenocytes reacting against the same target cells. This difference was accentuated when these cells were sensitized to host-type target cells prior to plating in limiting dilution cultures. In 1:1 mixing experiments of normal and chimeric splenocytes, there was no evidence of any in vitro suppressive activity to account for hyporeactivity of chimeric cells against host-type cells. Thus, maintenance of TLI-induced tolerance seemed not to be mediated primarily through an active suppressor cell mechanism

  1. Responses to Varroa by honey bees with different levels of Varroa Sensitive Hygiene

    Science.gov (United States)

    The mite-resistance trait called suppression of mite reproduction (SMR) is a form of hygienic behavior that we have named varroa sensitive hygiene (VSH). With VSH, adult worker bees (Apis mellifera) disrupt the population growth of parasitic mites (Varroa destructor) by removing mite-infested bee p...

  2. Resonantly enhanced nonlinear optics in semiconductor quantum wells: An application to sensitive infrared detection

    International Nuclear Information System (INIS)

    Yelin, S.F.; Hemmer, P.R.

    2002-01-01

    A novel class of coherent nonlinear optical phenomena, involving induced transparency in semiconductor quantum wells, is considered in the context of a particular application to sensitive long-wavelength infrared detection. It is shown that the strongest decoherence mechanisms can be suppressed or mitigated, resulting in substantial enhancement of nonlinear optical effects in semiconductor quantum wells

  3. Perceptual Sensitivity and Response to Strong Stimuli Are Related

    Directory of Open Access Journals (Sweden)

    Anna C. Bolders

    2017-09-01

    Full Text Available To shed new light on the long-standing debate about the (independence of sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the relation between these tendencies within the neurobehavioral framework of the Predictive and Reactive Control Systems (PARCS theory (Tops et al., 2010, 2014. Whereas previous studies only considered overreactivity in terms of the individual tendency to experience unpleasant affect (punishment reactivity resulting from strong sensory stimulation, we also took the individual tendency to experience pleasant affect (reward reactivity resulting from strong sensory stimulation into account. According to PARCS theory, these temperamental tendencies overlap in terms of high reactivity toward stimulation, but oppose each other in terms of the response orientation (approach or avoid. PARCS theory predicts that both types of reactivity to strong stimuli relate to sensitivity to weak stimuli, but that these relationships are suppressed due to the opposing relationship between reward and punishment reactivity. We measured punishment and reward reactivity to strong stimuli and sensitivity to weak stimuli using scales from the Adult Temperament Questionnaire (Evans and Rothbart, 2007. Sensitivity was also measured more objectively using the masked auditory threshold. We found that sensitivity to weak stimuli (both self-reported and objectively assessed was positively associated with self-reported punishment and reward reactivity to strong stimuli, but only when these reactivity measures were controlled for each other, implicating a mutual suppression effect. These results are in line with PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are dependent, but this dependency is likely to be obscured if punishment and reward reactivity are not both taken into account.

  4. Using Correlated Photons to Suppress Background Noise

    Science.gov (United States)

    Jackson, Deborah; Hockney, George; Dowling, Jonathan

    2003-01-01

    A proposed method of suppressing the effect of background noise in an optical communication system would exploit the transmission and reception of correlated photons at the receiver. The method would not afford any advantage in a system in which performance is limited by shot noise. However, if the performance of the system is limited by background noise (e.g., sunlight in the case of a free-space optical communication system or incoherently scattered in-band photons in the case of a fiber-optic communication system), then the proposed method could offer an advantage: the proposed method would make it possible to achieve a signal-to-noise ratio (S/N) significantly greater than that of an otherwise equivalent background- noise-limited optical communication system based on the classical transmission and reception of uncorrelated photons. The figure schematically depicts a classical optical-communication system and a system according to the proposed method. In the classical system, a modulated laser beam is transmitted along an optical path to a receiver, the optics of which include a narrow-band-pass filter that suppresses some of the background noise. A photodetector in the receiver detects the laser-beam and background photons, most or all of which are uncorrelated. In the proposed system, correlated photons would be generated at the transmitter by making a modulated laser beam pass through a nonlinear parametric down-conversion crystal. The sum of frequencies of the correlated photons in each pair would equal the frequency of the incident photon from which they were generated. As in the classical system, the correlated photons would travel along an optical path to a receiver, where they would be band-pass filtered and detected. Unlike in the classical system, the photodetector in the receiver in this system would be one that intrinsically favors the detection of pairs of correlated photons over the detection of uncorrelated photons. Even though there would be no

  5. Suitable level of suppression in Pinus sylvestris

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, Mats

    1999-10-01

    It is `well known` among Swedish foresters that pine trees need light and cannot grow suppressed. It is also `well known` that old trees that have grown slowly are unable to react with good growth. However, these facts can be questioned in the light of new research as it has been found that thinning reaction is not correlated with age. It is also well known that the commercial value of a pine is closely related to the growth at young age. If the first 20 annual rings close to pith are wide (>3 mm) the log cannot be accepted as first class. This is related to number and size of branches on the young tree and to the features of the juvenile wood. This is to say that a pine must not grow fast when it is small and if this has happened it cannot be cured by artificial debranching or by growing the tree slowly at higher age. Accordingly, young pines should be grown under bigger trees that in their young age were grown under big trees, and so on. Today, when clear cutting is the dominating forest management system, the only way to obtain high quality pine trees is to start the rotation age with stands of very high density. This is of course a very expensive way as dense planting, followed by intensive thinning requires a lot of input. However, if pine is a pioneer species and cannot be grown in multistoried stands, then the economic solution is not present. This was the reason why the annual increment of three pines was measured. They were selected because their different growth pattern showed that old `well known facts` should be revised Working papers 139. 3 refs, 7 figs, 1 tab

  6. Pocket Proteins Suppress Head and Neck Cancer

    Science.gov (United States)

    Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

    2012-01-01

    Head and neck squamous cell carcinomas (HNSCC) is a common cancer in humans long known to be caused by tobacco and alcohol use, but now an increasing percentage of HNSCC is recognized to be caused by the same human papillomaviruses (HPVs) that cause cervical and other anogenital cancers. HPV-positive HNSCCs differ remarkably from HPV-negative HNSCCs in their clinical response and molecular properties. From studies in mice, we know that E7 is the dominant HPV oncoprotein in head and neck cancer. E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene. However loss of pRb function does not fully account for E7’s potency in causing head and neck cancer. In this study, we characterized the cancer susceptibility of mice deficient in the expression of pRb and either of two related “pocket” proteins, p107 and p130, that are also inactivated by E7. pRb/p107 deficient mice developed head and neck cancer as frequently as do HPV16 E7 transgenic mice. The head and neck epithelia of the pRb/p107 deficient mice also displayed the same acute phenotypes and biomarker readouts as observed in the epithelia of E7 transgenic mice. Mice deficient for pRb and p130 in their head and neck epithelia showed intermediate acute and tumor phenotypes. We conclude that pRb and p107 act together to efficiently suppress head and neck cancer, and are therefore highly relevant targets of HPV16 E7 in its contribution to HPV-positive HNSCC. PMID:22237625

  7. Abdominal adipose tissue quantification on water-suppressed and non-water-suppressed MRI at 3T using semi-automated FCM clustering algorithm

    Science.gov (United States)

    Valaparla, Sunil K.; Peng, Qi; Gao, Feng; Clarke, Geoffrey D.

    2014-03-01

    Accurate measurements of human body fat distribution are desirable because excessive body fat is associated with impaired insulin sensitivity, type 2 diabetes mellitus (T2DM) and cardiovascular disease. In this study, we hypothesized that the performance of water suppressed (WS) MRI is superior to non-water suppressed (NWS) MRI for volumetric assessment of abdominal subcutaneous (SAT), intramuscular (IMAT), visceral (VAT), and total (TAT) adipose tissues. We acquired T1-weighted images on a 3T MRI system (TIM Trio, Siemens), which was analyzed using semi-automated segmentation software that employs a fuzzy c-means (FCM) clustering algorithm. Sixteen contiguous axial slices, centered at the L4-L5 level of the abdomen, were acquired in eight T2DM subjects with water suppression (WS) and without (NWS). Histograms from WS images show improved separation of non-fatty tissue pixels from fatty tissue pixels, compared to NWS images. Paired t-tests of WS versus NWS showed a statistically significant lower volume of lipid in the WS images for VAT (145.3 cc less, p=0.006) and IMAT (305 cc less, p1), but not SAT (14.1 cc more, NS). WS measurements of TAT also resulted in lower fat volumes (436.1 cc less, p=0.002). There is strong correlation between WS and NWS quantification methods for SAT measurements (r=0.999), but poorer correlation for VAT studies (r=0.845). These results suggest that NWS pulse sequences may overestimate adipose tissue volumes and that WS pulse sequences are more desirable due to the higher contrast generated between fatty and non-fatty tissues.

  8. The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia

    OpenAIRE

    Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P.; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

    2016-01-01

    Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated...

  9. Relationship between thermal stratification and flow patterns in steam-quenching suppression pool

    International Nuclear Information System (INIS)

    Song, Daehun; Erkan, Nejdet; Jo, Byeongnam; Okamoto, Koji

    2015-01-01

    Highlights: • Thermal stratification mechanism by direct contact condensation is investigated. • Thermal stratification condition changes according to the flow pattern. • Thermal stratification depends on the force balance between buoyancy and momentum. • Flow pattern change was observed even in the same regime. • Flow pattern is affected by the sensitive force balance. - Abstract: This study aims to examine the relationship between thermal stratification and flow patterns in a steam-quenching suppression pool using particle image velocimetry. Thermal stratification was experimentally evaluated in a depressurized water pool under different steam mass flux conditions. The time evolution of the temperature profile of the suppression pool was presented with the variation of condensation regimes, and steam condensation processes were visualized using a high-speed camera. The thermal stratification condition was classified into full mixing, gradual thermal stratification, and developed thermal stratification. It was found that the condition was determined by the flow patterns depending on the force balance between buoyancy and momentum. The force balance affected both the condensation regime and the flow pattern, and hence, the flow pattern was changed with the condensation regime. However, the force balance had a sensitive influence on the flow in the pool; therefore, distinct flow patterns were observed even in the same condensation regime.

  10. Suppression of the secondary flow in a suction channel of a large centrifugal pump

    International Nuclear Information System (INIS)

    Torii, D; Nagahara, T; Okihara, T

    2013-01-01

    The suction channel configuration of a large centrifugal pump with a 90-degree bend was studied in detail to suppress the secondary flow at the impeller inlet for improving suction performance. Design of experiments (DOE) and computational fluid dynamics (CFD) were used to evaluate the sensitivity of several primary design parameters of the suction channel. A DOE is a powerful tool to clarify the sensitivity of objective functions to design parameters with a minimum of trials. An L9 orthogonal array was adopted in this study and nine suction channels were designed, through which the flow was predicted by steady state calculation. The results indicate that a smaller bend radius with a longer straight nozzle, distributed between the bend and the impeller, suppresses the secondary flow at the impeller inlet. An optimum ratio of the cross sectional areas at the bend inlet and outlet was also confirmed in relationship to the contraction rate of the downstream straight nozzle. These findings were obtained by CFD and verified by experiments. The results will aid the design of large centrifugal pumps with better suction performance and higher reliability

  11. Suppression of in vitro cell-mediated lympholysis generation by alloactivated lymphocytes. Examination of radioresistant suppressive activity

    International Nuclear Information System (INIS)

    Orosz, C.G.; Ferguson, R.M.

    1986-01-01

    We investigated the radioresistant (1000 rads) suppression of CML generation mediated by alloactivated murine splenocytes. Suppressive cells were generated in MLCs by stimulation of (A X 6R)F1 splenocytes with irradiated C57BL/10 splenocytes. Suppressive cells could lyse targets bearing H-2b alloantigens, but would not lyse parental B10.T(6R) or B10.A targets. Suppressive activity was detected by including the alloactivated (A X 6R)F1 cells in B10.T(6R) anti-B10.A(1R) MLCs. Relative to the suppressive (A X 6R)F1 cells, the B10.A(1R) lymphocytes display both parental and suppressor-inducing alloantigens. In the absence of a suppressive population, B10.A(1R) stimulators cause B10.T(6R) splenocytes to generate cytolytic activity specific for both H-2Db (suppressor-inducing) and H-2Kk (suppressor-borne) target determinants. The irradiated, alloactivated (A X 6R)F1 cells decrease the H-2Db-specific CML generated in this system, thus mediating apparent antigen-specific suppression. However, cytolytic activity concomitantly generated in the same culture against the unrelated H-2Kk target determinants is similarly reduced by the (A X 6R)F1 cells. Thus, radioresistant suppression by alloactivated splenocytes is not necessarily antigen-specific. The irradiated (A X 6R)F1 cells would not suppress the generation of H-2Kk-specific CTL in B10.T(6R) anti-B10.A MLCs. Hence, the irradiated (A X 6R)F1 cells can impede CML generation against third-party alloantigens if, and only if, those alloantigens are coexpressed with suppressor-inducing alloantigens on the stimulator cells in suppressed MLCs. Similar results were also obtained using a different histoincompatible lymphocyte combination

  12. MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.

    Science.gov (United States)

    Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A; Pfeffer, Lawrence M

    2017-12-22

    Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro , and inhibited GBM tumorigenesis in vivo . Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro , and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway.

  13. Context Sensitive Health Informatics

    DEFF Research Database (Denmark)

    Kuziemsky, Craig; Nøhr, Christian; Aarts, Jos

    2013-01-01

    Context is a key consideration when designing and evaluating health information technology (HIT) and cannot be overstated. Unintended consequences are common post HIT implementation and even well designed technology may not achieve desired outcomes because of contextual issues. While context should...... be considered in the design and evaluation of health information systems (HISs) there is a shortcoming of empirical research on contextual aspects of HIT. This conference integrates the sociotechnical and Human-Centered-Design (HCD) approaches and showcases current research on context sensitive health...... informatics. The papers and presentations outlines theories and models for studying contextual issues and insights on how we can better design HIT to accommodate different healthcare contexts....

  14. Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Di Wei

    2010-03-01

    Full Text Available Dye sensitized solar cell (DSSC is the only solar cell that can offer both the flexibility and transparency. Its efficiency is comparable to amorphous silicon solar cells but with a much lower cost. This review not only covers the fundamentals of DSSC but also the related cutting-edge research and its development for industrial applications. Most recent research topics on DSSC, for example, applications of nanostructured TiO2, ZnO electrodes, ionic liquid electrolytes, carbon nanotubes, graphene and solid state DSSC have all been included and discussed.

  15. Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz

    Multiple chemical sensitivity (MCS) is a chronic disorder characterized by reports of symptoms from various organ systems attributed by the individuals to exposure to common odors and airborne chemicals in doses far below those known to induce toxic effects. There exists a general lack of knowledge......, significantly reduced levels of IL-13 in the MCS group and no group differences in the allergen specific IgE measures. The differences were independent of factors such as sex, age, Body Mass Index, asthma, smoking, depression, anxiety and allergen-specific IgE. In conclusion, the study identified a distinct...

  16. Cross-cultural differences in emotion suppression in everyday interactions.

    Science.gov (United States)

    Huwaë, Sylvia; Schaafsma, Juliette

    2016-05-11

    Previous research suggests that in collectivistic cultures, people tend to suppress their emotions more than in individualistic cultures. Little research, however, has explored cross-cultural differences in emotion regulation in everyday interactions. Using a daily social interaction method, we examined whether people from collectivistic backgrounds (Chinese exchange students and immigrants from the Moluccas, Indonesia) living in the Netherlands differed from those from individualistic backgrounds (Dutch natives) in emotion suppression during everyday interactions. We also examined whether this depended on their relationship with the interaction partner(s). We found that Chinese participants suppressed positive and negative emotions more than Dutch and Moluccan participants and that this was related to differences in interdependent and independent self-construal across the samples. We also found that Chinese participants suppressed positive emotions less in interactions with close others, whereas Dutch participants suppressed negative emotions more with non-close others. No such differences were found for Moluccans. Our findings support the idea that people from collectivistic cultures suppress emotions more than those from individualistic cultures, but they also suggest that this depends on who the interaction partner is. Furthermore, they suggest that emotion suppression may change when people with collectivistic backgrounds have been raised in individualistic cultures. © 2016 International Union of Psychological Science.

  17. Radiosensitivities of sensitized lymphocytes

    International Nuclear Information System (INIS)

    Taniguchi, Kazuto

    1979-01-01

    Immunization of mice with cell antigens such as allogeneic tumor cells or xenogeneic erythrocytes raises a variety of immune reactions mediated by T lymphocytes: i.e. delayed type hypersensitivity (DTH), cytotoxicity, and antibody production. The radiosensitivities of these reactions were examined in mice exposed to 600 R x-irradiation a few hours before or after immunization. 1) DTH to xenogeneic erythrocytes, as demonstrated by footpad reaction, was not suppressed by irradiation 3 h before or after immunization. DTH to allogeneic tumor cells, as demonstrated by a migration inhibition test, hardly developed in mice that had been irradiated before or after immunization. It may have belonged to distinct types of delayed reactions which were mediated by distinct subpopulations of T lymphocytes. 2) Cytotoxicity against allogeneic cells and xenogeneic erythrocytes showed almost the same radiosensitivity. It was scarcely detected in mice that had been irradiated before immunization. However, a low but definite degree of cytotoxicity was detected in mice that had been irradiated only a few hours after immunization. Solubilized allogeneic cells instead of native cells were used as immunizing antigens. It was also possible for precursor cells with cytotoxicity to acquire a radioresistant nature by immunization of solubilized antigens, but native cells were required as stimulation for radioresistant precursor cells to differentiated into nature cytotoxic effector cells. 3) Antibody production against xenogeneic erythrocytes or allogeneic cells was almost completely depleted in mice that had been irradiated before or after immunization. It is possible that antibody production essentially requires cell division and clonal expansion of B lymphocytes. (Bell, E.)

  18. Comparative Metatranscriptomics of Wheat Rhizosphere Microbiomes in Disease Suppressive and Non-suppressive Soils for Rhizoctonia solani AG8

    Directory of Open Access Journals (Sweden)

    Helen L. Hayden

    2018-05-01

    Full Text Available The soilborne fungus Rhizoctonia solani anastomosis group (AG 8 is a major pathogen of grain crops resulting in substantial production losses. In the absence of resistant cultivars of wheat or barley, a sustainable and enduring method for disease control may lie in the enhancement of biological disease suppression. Evidence of effective biological control of R. solani AG8 through disease suppression has been well documented at our study site in Avon, South Australia. A comparative metatranscriptomic approach was applied to assess the taxonomic and functional characteristics of the rhizosphere microbiome of wheat plants grown in adjacent fields which are suppressive and non-suppressive to the plant pathogen R. solani AG8. Analysis of 12 rhizosphere metatranscriptomes (six per field was undertaken using two bioinformatic approaches involving unassembled and assembled reads. Differential expression analysis showed the dominant taxa in the rhizosphere based on mRNA annotation were Arthrobacter spp. and Pseudomonas spp. for non-suppressive samples and Stenotrophomonas spp. and Buttiauxella spp. for the suppressive samples. The assembled metatranscriptome analysis identified more differentially expressed genes than the unassembled analysis in the comparison of suppressive and non-suppressive samples. Suppressive samples showed greater expression of a polyketide cyclase, a terpenoid biosynthesis backbone gene (dxs and many cold shock proteins (csp. Non-suppressive samples were characterised by greater expression of antibiotic genes such as non-heme chloroperoxidase (cpo which is involved in pyrrolnitrin synthesis, and phenazine biosynthesis family protein F (phzF and its transcriptional activator protein (phzR. A large number of genes involved in detoxifying reactive oxygen species (ROS and superoxide radicals (sod, cat, ahp, bcp, gpx1, trx were also expressed in the non-suppressive rhizosphere samples most likely in response to the infection of wheat

  19. Procedures for Sensitive Immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Givol, D. [Department of Chemical Immunology, Weizmann Institute of Science, Rehovot (Israel)

    1970-02-15

    Sensitive immunoassay methods should be applied to small molecules of biological importance, which are non-immunogenic by themselves, such as small peptide hormones (e.g. bradykinin), plant hormones (e.g. indoleacetic acid), nucleotides and other small molecules. Methods of binding these small molecules, as haptens, to immunogenic carriers by various cross-linking agents are described (dicyclohexylcarbodiimide, tolylene-diisocyanate and glutaraldehyde), and the considerations involved in relation to the methods of binding and the specificity of the antibodies formed are discussed. Some uses of antibody bound to bromoacetyl cellulose as an immuno adsorbent convenient for assay of immunoglobulins are described. Finally, the sensitive immunoassay method of chemically modified phage is described. This includes methods of binding small molecules (such as the dinitrophenyl group, penicillin, indoleacetic acid) or proteins (such as insulin, immunoglobulins) to phages. Methods of direct chemical conjugation, or an indirect binding via anti-phage Fab, are described. The phage inactivation method by direct plating and its modifications (such as decision technique and complex inactivation) are compared with the more simple end-point titration method. The inhibition of phage inactivation has some advantages as it does not require radioactive material, or expensive radioactive counters, and avoids the need for separation between bound and unbound antigen. Hence, if developed, it could be used as an alternative to radioimmunoassay. (author)

  20. [Sensitization to Lyral].

    Science.gov (United States)

    Heras, F; Díaz-Recuero, J L; Cabello, M J; Conde-Salazar, L

    2006-01-01

    Lyral is a fragrance that is present in many cosmetic products. It has turned into an emergent allergen during the last years. In studies carried out in other European countries, the prevalence of sensitization to Lyral has been found to be 1.9-2.7 %, but it is unknown the prevalence in Spain, as well as the need to include it or not in the standard series of the Spanish Group of Contact Dermatitis (GEIDC). We have patch-tested to Lyral all patients with suspicion of contact dermatitis of any origin who attended our Service between April and May-2005. From a total of 170 patients included in our study, 2 of them had a sensitization to Lyral (1.2 %). One of these two patients had an axillae contact dermatitis caused by a deodorant containing Lyral. The other patient was a masseur-woman with a contact dermatitis on both hands, with periods of dissemination to upper extremities and trunk, and who used several cosmetics products for private reasons and during her job. Although the sample of this study is quite small, we think that the results allow to suspect that Lyral is one of the main allergens, or even the most important, in causing allergic contact dermatitis to fragrances in our environment. Therefore, we believe that we must raise the inclusion of Lyral in the standard series of GEIDC, either as independent allergen, or including it in a new mixture of fragrances.