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Sample records for suppressing capsaicin-induced sensitization

  1. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger

    2011-01-01

    in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare).......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...

  2. Capsaicin-induced central sensitization evokes segmental increases in trigger point sensitivity in humans.

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    Srbely, John Z; Dickey, James P; Bent, Leah R; Lee, David; Lowerison, Mark

    2010-07-01

    This study investigated whether inducing central sensitization evokes segmental increases in trigger point pressure sensitivity. We evoked central sensitization at the C(5) segment and validated its presence via mechanical cutaneous sensitivity (brush allodynia) testing. Trigger point pressure sensitivity was quantified using the pain pressure threshold (PPT) value. A 50 cm(2) area of the C(5) dermatome at the right lateral elbow was pretreated with 45 degrees heat for 10 minutes. Test subjects (n = 20) then received topical capsaicin cream (0.075%; Medicis, Toronto, Canada) to the C(5) dermatome, whereas control subjects (n = 20) received a topical placebo cream (Biotherm Massage, Montreal, Canada). PPT readings were recorded from the infraspinatus (C(5,6)) and gluteus medius (L(4,5)S(1)) trigger points at zero (pre-intervention), 10, 20, and 30 minutes after intervention; all PPT readings were normalized to pre-intervention (baseline) values. The difference between the PPT readings at the 2 trigger point sites represents the direct influence of segmental mechanisms on the trigger point sensitivity at the infraspinatus site (PPT(seg)). Test subjects demonstrated statistically significant increases in Total Allodynia scores and significant decreases in PPT(seg) at 10, 20, and 30 minutes after application, when compared with control subjects. These results demonstrate that increases in central sensitization evoke increases in trigger point pressure sensitivity in segmentally related muscles. Myofascial pain is the most common form of musculoskeletal pain. Myofascial trigger points play an important role in the clinical manifestation of myofascial pain syndrome. Elucidating the role of central sensitization in the pathophysiology of trigger points is fundamental to developing optimal strategies in the management of myofascial pain syndrome.

  3. Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.

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    Lam, D K; Sessle, B J; Hu, J W

    2008-10-15

    Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central

  4. Down-regulation of tumor-associated NADH oxidase, tNOX (ENOX2), enhances capsaicin-induced inhibition of gastric cancer cell growth.

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    Wang, His-Ming; Chuang, Show-Mei; Su, Yu-Ching; Li, Yi-Hui; Chueh, Pin Ju

    2011-11-01

    Gastric cancer is a common human malignancy and a major contributor to cancer-related deaths worldwide. Unfortunately, the prognosis of most gastric cancer patients is poor because they are generally diagnosed at a late stage after the cancer has already metastasized. Most current research, therefore, emphasizes selective targeting of cancer cells by apoptosis-inducing agents. One such therapeutic agent is capsaicin, a component of chili peppers that has been shown to possess anti-growth activity against various cancer cell lines. Here, we examined the effect of capsaicin on SNU-1 and TMC-1 gastric cancer cells and found differing outcomes between the two cell lines. Our results show that capsaicin induced significant cytotoxicity with increases in oxidative stress, PARP cleavage, and apoptosis in sensitive SNU-1 cells. In contrast, TMC-1 cells were much less sensitive to capsaicin, exhibiting low cytotoxicity and very little apoptosis in response to capsaicin treatment. Capsaicin-induced apoptosis in SNU-1 cells was associated with down-regulation of tumor-associated NADH oxidase (tNOX) mRNA and protein. On the contrary, tNOX expression was scarcely affected by capsaicin in TMC-1 cells. We further showed that tNOX-knockdown sensitized TMC-1 cells to capsaicin-induced apoptosis and G1 phase accumulation, and led to decreased cell growth, demonstrating that tNOX is essential for cancer cell growth. Collectively, these results indicate that capsaicin induces divergent effects of the growth of gastric cancer cells that parallel its effects on tNOX expression, and demonstrate that forced tNOX down-regulation restored capsaicin-induced growth inhibition in TMC-1 cells.

  5. 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.

  6. Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

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    Carsten Zschenderlein

    2011-01-01

    Full Text Available The transient receptor potential vanilloid type 1 (TRPV1 channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA. Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1, AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

  7. Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia.

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    Morris, V; Cruwys, S; Kidd, B

    1998-07-10

    In this study, capsaicin-induced secondary hyperalgesia was assessed as a marker of abnormal nociceptive processing in patients with fibromyalgia (FM). The area of mechanical secondary hyperalgesia induced by a standard solution of capsaicin placed on the volar forearm was measured in ten patients with FM and the results compared to those obtained in ten patients with rheumatoid arthritis (RA) and ten normal subjects. The area of secondary hyperalgesia was found to be substantially increased in both the FM and RA groups compared with controls. In the FM group the area of hyperalgesia correlated with the overall pain score and with the joint tenderness score. The results suggest that in FM there is enhanced sensitivity of nociceptive neurones at a spinal level, thereby supporting the concept of a generalised disturbance of pain modulation in this disorder.

  8. Mechanisms underlying the augmentation of phenylbiguanide and capsaicin induced cardiorespiratory reflexes by Mesobuthus tamulus venom.

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    Dutta, Abhaya; Akella, Aparna; Deshpande, Shripad B

    2012-10-01

    Phenylbiguanide (PBG) and capsaicin evoke cardiorespiratory reflexes utilizing two separate pathways. It is known that Indian Red Scorpion (Mesobuthus tumulus; MBT) venom augments PBG (5-HT(3)) responses but, the effect of MBT venom on capsaicin (TRPV1)-induced response is not known. Therefore, the present study was undertaken to ascertain whether MBT venom also augments the capsaicin-induced reflex responses involving mechanisms similar to PBG. Experiments were performed on anaesthetized adult rats. Blood pressure, respiratory excursions and ECG were recorded. At the end of each experiment pulmonary water content was determined. PBG (10 μg/kg) produced hypotension, bradycardia and apnoea-bradypnoea. Capsaicin (10 μg/kg) also produced hypotension, bradycardia and apnoea-bradypnoea. MBT venom (100 μg/kg) augmented PBG as well as capsaicin-induced responses and produced pulmonary oedema (increased pulmonary water content). Prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) blocked the venom-induced augmentation of PBG and capsaicin reflexes. Kinin synthase inhibitor (aprotinin; 6000 KIU) and guanylate cyclase (GC) inhibitor (methylene blue; 5 mg/kg) blocked the venom-induced augmentation of PBG response but not the capsaicin response. However, pulmonary oedema was blocked by these antagonists. Phosphodiesterase V inhibitor (sildenafil; 100 μg/kg) augmented the PBG response but not the capsaicin response, though pulmonary oedema was seen in both the groups. The present results indicate that MBT venom also augments the capsaicin-induced responses. The augmentation of capsaicin response involves PGs and pulmonary oedema-independent mechanisms whereas, the augmentation of PBG response involves kinin mediated GC-cGMP pathway and pulmonary oedema-dependent mechanisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. 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…

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

    DEFF Research Database (Denmark)

    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...

  11. Local administration of Δ9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys: a peripheral cannabinoid action

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    Ko, Mei-Chuan; Woods, James H.

    2010-01-01

    Rationale Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents. Objectives The study was conducted to evaluate the hypothesis that local administration of Δ9-tetrahydrocannabinol (Δ9-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Methods Capsaicin (100 µg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46°C water. Δ9-THC (10–320 µg) was coadministered with capsaicin in the tail to assess local antinociceptive effects. In addition, a local antagonism study was performed to confirm the selectivity of Δ9-THC action. Results Δ9-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10–100 µg) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 µg SR141716A injected subcutaneously in the back did not antagonize local Δ9-THC. Conclusions These results indicate that the site of action of locally applied Δ9-THC is in the tail. It provides functional evidence that activation of peripheral cannabinoid CB1 receptors can attenuate capsaicin-induced thermal nociception in non-human primates and suggests a new approach for cannabinoids in pain management. PMID:10353438

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

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    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 concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...

  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. Anti-nociceptive and desensitizing effects of olvanil on capsaicin-induced thermal hyperalgesia in the rat.

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    Alsalem, Mohammad; Millns, Paul; Altarifi, Ahmad; El-Salem, Khalid; Chapman, Victoria; Kendall, David A

    2016-07-21

    Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil's anti-hyperalgesic effects were also investigated. A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced thermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies of DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses. Statistical analysis used Student's t test or one way ANOVA followed by Dunnett's post-hoc test as appropriate. Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium concentrations [Ca(2+)]i in cultured DRG neurons. Olvanil was able to desensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intraplantar injection of capsaicin (0.1, 0.3 and 1 μg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1 μg) produced no hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1 μg) altered neither capsaicin-induced thermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1 receptors. Olvanil is effective in reducing

  15. Capsaicin-induced Ca2+signaling is enhanced via upregulated TRPV1 channels in pulmonary artery smooth muscle cells from patients with idiopathic PAH.

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    Song, Shanshan; Ayon, Ramon J; Yamamura, Aya; Yamamura, Hisao; Dash, Swetaleena; Babicheva, Aleksandra; Tang, Haiyang; Sun, Xutong; Cordery, Arlette G; Khalpey, Zain; Black, Stephen M; Desai, Ankit A; Rischard, Franz; McDermott, Kimberly M; Garcia, Joe G N; Makino, Ayako; Yuan, Jason X-J

    2017-03-01

    Capsaicin is an active component of chili pepper and a pain relief drug. Capsaicin can activate transient receptor potential vanilloid 1 (TRPV1) channels to increase cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ). A rise in [Ca 2+ ] cyt in pulmonary artery smooth muscle cells (PASMCs) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. In this study, we observed that a capsaicin-induced increase in [Ca 2+ ] cyt was significantly enhanced in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with normal PASMCs from healthy donors. In addition, the protein expression level of TRPV1 in IPAH PASMCs was greater than in normal PASMCs. Increasing the temperature from 23 to 43°C, or decreasing the extracellular pH value from 7.4 to 5.9 enhanced capsaicin-induced increases in [Ca 2+ ] cyt ; the acidity (pH 5.9)- and heat (43°C)-mediated enhancement of capsaicin-induced [Ca 2+ ] cyt increases were greater in IPAH PASMCs than in normal PASMCs. Decreasing the extracellular osmotic pressure from 310 to 200 mOsmol/l also increased [Ca 2+ ] cyt , and the hypo-osmolarity-induced rise in [Ca 2+ ] cyt was greater in IPAH PASMCs than in healthy PASMCs. Inhibition of TRPV1 (with 5'-IRTX or capsazepine) or knockdown of TRPV1 (with short hairpin RNA) attenuated capsaicin-, acidity-, and osmotic stretch-mediated [Ca 2+ ] cyt increases in IPAH PASMCs. Capsaicin induced phosphorylation of CREB by raising [Ca 2+ ] cyt , and capsaicin-induced CREB phosphorylation were significantly enhanced in IPAH PASMCs compared with normal PASMCs. Pharmacological inhibition and knockdown of TRPV1 attenuated IPAH PASMC proliferation. Taken together, the capsaicin-mediated [Ca 2+ ] cyt increase due to upregulated TRPV1 may be a critical pathogenic mechanism that contributes to augmented Ca 2+ influx and excessive PASMC proliferation in patients with IPAH. Copyright © 2017 the American Physiological Society.

  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. 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.

  18. 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.

  19. Neural proliferation and restoration of neurochemical phenotypes and compromised functions following capsaicin-induced neuronal damage in the nodose ganglion of the adult rat.

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    Zachary Rex Gallaher

    2011-02-01

    Full Text Available We previously reported that neuronal numbers within adult nodose ganglia (NG were restored to normal levels 60 days following the capsaicin-induced destruction of nearly half of the neuronal population. However, the nature of this neuronal replacement is not known. Therefore, we aimed to characterize neural proliferation, neurochemical phenotypes, and functional recovery within adult rat NG neurons following capsaicin-induced damage. Sprague-Dawley rats received intraperitoneal injections of capsaicin or vehicle solution, followed by BrdU injections to reveal cellular proliferation. NG were collected at multiple times post-treatment (up to 300 days and processed for immunofluorescence, real-time RT-PCR, and dispersed cell cultures. Capsaicin-induced cellular proliferation, indicated by BrdU/Ki-67-labeled cells, suggests that lost neurons were replaced through cell division. NG cells expressed the stem cell marker, nestin, indicating that these ganglia have the capacity to generate new neurons. BrdU incorporation within beta-III tubulin-positive neuronal profiles following capsaicin suggests that proliferating cells matured to become neurons. NG neurons displayed decreased NMDAR expression up to 180 days post-capsaicin. However, both NMDAR expression within the NG and synaptophysin expression within the central target of NG neurons, the NTS, were restored to pre-injury levels by 300 days. NG cultures from capsaicin-treated rats contained bipolar neurons, normally found only during development. To test the functional recovery of NG neurons, we injected the satiety molecule, CCK. The effect of CCK on food intake was restored by 300 days post-capsaicin. This restoration may be due to the regeneration of damaged NG neurons or generation of functional neurons that replaced lost connections.

  20. 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.

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

    Science.gov (United States)

    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).

  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-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.

  5. 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.

  6. Analgesic effect of subcutaneous administration of oxygen-ozone. A blind study in the rat on the modulation of the capsaicin-induced edema.

    Science.gov (United States)

    Ceccherelli, F; Gagliardi, G; Faggian, L; Loprete, F; Giron, G

    1998-01-01

    The Authors have explored a new complementary approach, employed in the last 40 years for, among other uses, medical purposes: oxygen-ozone therapy. Anecdotal works have highlighted interesting results obtained in disk herniation with infiltration of paravertebral muscles with oxygen-ozone. To verify the existence of a nociceptive effect and investigate a possible mechanism of action, an experimental model of edema induction by subcutaneous capsaicin injection in the rat paw was employed. Oxygen-ozone, in different concentrations (10 microg/ml, 20 microg/ml and 30 microg/ml) has been injected both ipsi- and contralaterally to the paw 30 minutes before the administration of 50 microg capsaicin in 50 microl of physiological solution. Results show that the contralateral injection of the O2-O3 mixture modulates the edema response in the paw. Statistical significance, for the 20 microg/ml mixture, lasts as far as 45 minutes after administration of the capsaicin. No efficacy has been found for the 10 and 30 microg/ml concentrations. An injection of the same quantity of gas in the ipsilateral paw to the capsaicin-induced edema determines a worse edema than that observed in the control group, as if the ozone mixture added its irritative effect to that of capsaicin. It is interesting to note that the administration of oxygen alone cause a greater edema than the oxygen-ozone mixture.

  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. 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.

  9. Facilitation by endogenous prostaglandins of capsaicin-induced gastric protection in rodents through EP2 and IP receptors.

    Science.gov (United States)

    Takeuchi, Koji; Kato, Shinichi; Takeeda, Masanori; Ogawa, Yoshihiro; Nakashima, Masato; Matsumoto, Masahiro

    2003-03-01

    We investigated the role that prostaglandins (PGs) and EP receptors play in facilitating the gastroprotective action of capsaicin against HCl/ethanol in rats and mice. Male Sprague-Dawley rats and C57BL/6 mice were used after 18 h of fasting. The animals were given HCl/ethanol (60% in 150 mM HCl) p.o. and killed 1 h later. Capsaicin or various EP agonists were given p.o. 30 min or i.v. 10 min before HCl/ethanol. In some cases, indomethacin or various EP agonists were given s.c. 30 min or i.v 10 min before capsaicin, respectively. Gastric lesions induced by HCl/ethanol were significantly inhibited by PGE(2) as well as capsaicin. The effect of PGE(2) was antagonized by ONO-AE-829 (EP1 antagonist), whereas the capsaicin action was mitigated by indomethacin as well as sensory deafferentation but not by ONO-AE-829. The generation of mucosal PGE(2) was not affected by either capsaicin or sensory deafferentation, but was significantly inhibited by indomethacin. Although neither butaprost (EP2), ONO-NT-012 (EP3), nor 11-deoxy PGE1 (EP4) alone had any effect on HCl/ethanol-induced gastric lesions, only butaprost restored the protective action of capsaicin in the presence of indomethacin. Capsaicin provided a protective action against HCl/ethanol-induced gastric lesions in wild-type (+/+) mice in an indomethacin-sensitive manner, and this action was similarly observed in EP1 (-/-) and EP3 (-/-) mice but not in the animals lacking IP receptors. These results suggest that capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous PGs through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin.

  10. Effect of chronic stress on capsaicin-induced dental nociception in a model of pulpitis in rats.

    Science.gov (United States)

    Raoof, Maryam; Ashrafganjoui, Ehsan; Kooshki, Razieh; Abbasnejad, Mehdi; Haghani, Jahangir; Amanpour, Sara; Zarei, Mohammad-Reza

    2018-01-01

    Chronic stress can alter nociceptive sensitivity. However, the effect of stress exposure on dental nociception has been less addressed. Therefore, the present study investigated the effects of chronic exposures to some social and psychological stresses on pulpal nociceptive responses. The stress groups were constructed as follows: forced swimming (n=6), restraint (n=6), and mild (n=10) and severe (n=15) crowding stresses. Rats were subjected to stress for 1h per day for a week. At the end of the stress session, pulp irritation was induced by intradental application of capsaicin (100μg). There were another capsaicin or capsaicin plus stress training groups that received articaine 5min before the administration of capsaicin. Nociceptive responses were recorded for 40min. The time (ins) of continuous shaking of the lower jaw and excessive grooming and rubbing of the mouth near the procedure site was measured as nociceptive behaviors. Data was analyzed using one-way analysis of variance (ANOVA) followed by post hoc Tukey's test. Significant nociceptive responses were evoked by the administration of capsaicin. Exposures to forced swimming (pstresses (pstress groups. Articaine buccal infiltration attenuated nociceptive time in capsaicin and capsaicin plus stress training groups (pstress exposures and nociceptive behavior following intradental capsaicin administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Gradient-enhanced TOCSY experiments with improved sensitivity and solvent suppression.

    Science.gov (United States)

    Fulton, D B; Hrabal, R; Ni, F

    1996-09-01

    Gradient-enhanced versions of the homonuclear TOCSY experiment are described, with solvent suppression and sensitivity superior to that of a conventional TOCSY experiment. The pulse sequences are constructed by appending a WATERGATE module to a z-filtered TOCSY experiment. Pulsed-field gradients and appropriately phased selective rf pulses are used to maintain precise control of the water magnetization vector. Problems associated with radiation damping and spin-locking of the water magnetization are thus alleviated. The water magnetization is returned to equilibrium prior to each acquisition, which improves water suppression and minimizes signal losses due to saturation transfer.

  12. 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.

  13. NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons

    Science.gov (United States)

    Nadeau, H.; Lester, H. A.

    2002-01-01

    The neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.

  14. A streptomycin-resistant Escherichia coli mutant with ribosomes temperature-sensitive in the suppression of a nonsense codon.

    Science.gov (United States)

    Zeevi, M; Daniel, V; Engelberg-Kulka, H

    1979-02-26

    Cell free extracts from a streptomycin-resistant E. coli mutant which is also temperature-sensitive for Q beta phage were studied for suppression of a nonsense mutation at various temperatures. The streptomycin-resistant ribosomes of the mutant were found to be temperature-sensitive in suppression of an amber mutation in f2 phage coat protein while retaining the ability to synthesize proteins at an elevated temperature (42 degrees C). The restriction of amber suppression at 42 degrees C is assumed to be related to an alteration in ribosomal protein S12 of the streptomycin-resistant mutant which also causes a change in its electrophoretic mobility.

  15. Activation of the aryl hydrocarbon receptor suppresses sensitization in a mouse peanut allergy model.

    Science.gov (United States)

    Schulz, V J; Smit, J J; Willemsen, K J; Fiechter, D; Hassing, I; Bleumink, R; Boon, L; van den Berg, M; van Duursen, M B M; Pieters, R H H

    2011-10-01

    Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T(reg)) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T(reg) cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T(reg) cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR(b)(-2)) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 μg/kg body weight) on days 3 and 11 orally. The functional role of CD4(+)CD25(+)Foxp3(+) T(reg) cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4(+)CD25(+)Foxp3(+) T(reg) cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4(+)CD25(+)Foxp3(+) T(reg) cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4(+) cell population toward CD4(+)CD25(+)Foxp3(+) T(reg) cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases.

  16. Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA

    Science.gov (United States)

    Gonzales, Patrick R.; Pesesky, Mitchell W.; Bouley, Renee; Ballard, Anna; Biddy, Brent A.; Suckow, Mark A.; Wolter, William R.; Schroeder, Valerie A.; Burnham, Carey-Ann D.; Mobashery, Shahriar; Chang, Mayland; Dantas, Gautam

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem/piperacillin/tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA N315 and 72 clinical MRSA isolates in vitro, and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem/penicillin/β-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to β-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein 2a (PBP2a) action via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing similar in vivo activity to linezolid, ME/PI/TZ demonstrates that combinations of older β-lactam antibiotics could be effective against MRSA infections in humans. PMID:26368589

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells.

    Science.gov (United States)

    Zhou, Jing; Hu, Shuai-Er; Tan, Shi-Hao; Cao, Ruoxi; Chen, Yiyang; Xia, Dajing; Zhu, Xinqiang; Yang, Xing-Fen; Ong, Choon-Nam; Shen, Han-Ming

    2012-03-01

    Suppression of autophagy has been increasingly recognized as a novel cancer therapeutic approach. Andrographolide (Andro), a diterpenoid lactone isolated from an herbal plant Andrographis paniculata, is known to possess anti-inflammatory and anticancer activity. In this study, we sought to examine the effect of Andro on autophagy, and to evaluate whether such effect is relevant to the sensitization effect of Andro on apoptosis induced by DNA damage agents in cancer cells. First, we found that Andro is able to significantly enhance autophagic markers in various cancer cell lines, including GFP-LC3 puncta and LC3-II level. Interestingly, Andro treatment also led to marked increase of p62 protein level and addition of chloroquine (CQ) failed to further enhance either LC3-II or p62 level, indicating that Andro is likely to suppress autophagic flux at the maturation and degradation stage. Next, we provided evidence that Andro inhibits autophagosome maturation not by affecting the lysosomal function, but by impairing autophagosome-lysosome fusion. Lastly, we demonstrated that treatment with cisplatin, a DNA damage agent, induces autophagy in cancer cells. Importantly, Andro is capable of sensitizing cisplatin-induced cell killing determined with both short-term apoptosis assays and long-term clonogenic test, via suppression of autophagy, a process independent of p53. In summary, these observations collectively suggest that Andro could be a promising anti-cancer agent in combination therapy via its potent inhibitory effect on autophagy by disrupting autophagosome-lysosome fusion.

  2. 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

  3. 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.

  4. Synergistic recombination suppression by an inorganic layer and organic dye molecules in highly photostable quantum dot sensitized solar cells.

    Science.gov (United States)

    Shen, Heping; Li, Jianbao; Zhao, Lin; Zhang, Shanshan; Wang, Wenli; Oron, Dan; Lin, Hong

    2014-04-07

    An inorganic layer and dye molecules have synergistically suppressed the recombination in a quantum dot sensitized solar cell (QDSSC), by the design of a structure featured TiO2-CdS-ZnS-N3 (N3: RuL2(NCS)2 (L = 2,2'-bipyridyl-4,4'-dicarboxylic acid)) hybrid photoanode. When fabricated into solar cells, a cobalt complex-based electrolyte rather than an iodine-based one was employed to obtain an impressive photostability for the devices. Raman and Photoluminescence (PL) measurements revealed that not only the CdS QDs were passivated by both the inorganic layer of ZnS and dye molecule of N3, but also N3 served as an efficient hole scavenger for the CdS QDs due to a type-II energetic alignment between the two sensitizers. This role of N3 as an intermediary in hole extraction from CdS QDs to the electrolyte was further proven by the significant photovoltaic performance improvement of the CdS sensitized solar cell after ZnS deposition and N3 co-sensitization. The overall efficiency of the solar cell incorporated with TiO2-CdS-ZnS-N3 film exceeded the sum of the single CdS QDs and N3 dye sensitized solar cells. This enhancement is ascribed mainly to the synergistic recombination suppression by the inorganic layer ZnS and N3 co-sensitization, leading to inhibited recombination and increased electron lifetime, as illustrated by the electrochemical impedance spectroscopy (EIS) analysis.

  5. 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.

  6. 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

  7. 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.

  8. Multicopy Fzf1 (Sul1) Suppresses the Sulfite Sensitivity but Not the Glucose Derepression or Aberrant Cell Morphology of a Grr1 Mutant of Saccharomyces Cerevisiae

    OpenAIRE

    Avram, D.; Bakalinsky, A. T.

    1996-01-01

    An ssu2 mutation in Sacccharomyces cerevisiae, previously shown to cause sulfite sensitivity, was found to be allelic to GRR1, a gene previously implicated in glucose repression. The suppressor rgt1, which suppresses the growth defects of grr1 strains on glucose, did not fully suppress the sensitivity on glucose or nonglucose carbon sources, indicating that it is not strictly linked to a defect in glucose metabolism. Because the Cln1 protein was previously shown to be elevated in grr1 mutants...

  9. 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.

  10. 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.

  11. Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction

    International Nuclear Information System (INIS)

    Schulze-Bergkamen, Henning; Fleischer, Binje; Schuchmann, Marcus; Weber, Achim; Weinmann, Arndt; Krammer, Peter H; Galle, Peter R

    2006-01-01

    Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. RNA interference was performed by transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl-1 expression was measured by quantitative real-time PCR and Western blot. Induction of apoptosis and caspase activity after treatment with chemotherapeutic drugs and different targeted therapies were measured by flow cytometry and fluorometric analysis, respectively. Here we demonstrate that Mcl-1 expressing HCC cell lines show low sensitivity towards treatment with a panel of chemotherapeutic drugs. However, treatment with the anthracycline derivative epirubicin resulted in comparatively high apoptosis rates in HCC cells. Inhibition of the kinase PI3K significantly increased apoptosis induction by chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic agents. Sensitization was accompanied by profound activation of caspase-3 and -9. In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis sensitivity towards combined treatment modalities: Mcl-1

  12. Allele-specific suppression of the temperature sensitivity of fitA/fitB ...

    Indian Academy of Sciences (India)

    The temperature sensitive transcription defective mutant of Escherichia coli originally called fitA76 has been shown to harbour two missense mutations namely pheS5 and fit95. In order to obtain a suppressor of fitA76, possibly mapping in rpoD locus, a Ts+ derivative (JV4) was isolated from a fitA76 mutant. It was found that ...

  13. 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

  14. 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

  15. Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold

    Science.gov (United States)

    McCoy, Eric S.; Taylor-Blake, Bonnie; Street, Sarah E.; Pribisko, Alaine L.; Zheng, Jihong; Zylka, Mark J.

    2013-01-01

    SUMMARY Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosensory neurons. Despite years of research, it is unknown if these neurons are required to sense pain or other sensory stimuli. Here, we found that genetic ablation of CGRPα-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or β-alanine itch—stimuli associated with nonpeptidergic sensory neurons. Unexpectedly, ablation enhanced behavioral responses to cold stimuli and cold mimetics without altering peripheral nerve responses to cooling. Mechanistically, ablation reduced tonic and evoked activity in postsynaptic spinal neurons associated with TRPV1/heat, while profoundly increasing tonic and evoked activity in spinal neurons associated with TRPM8/cold. Our data reveal that CGRPα sensory neurons encode heat and itch and tonically cross-inhibit cold-responsive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception. PMID:23523592

  16. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

    Science.gov (United States)

    Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

    2015-10-21

    Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice

    Science.gov (United States)

    Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W.; Zhang, Gongliang

    2015-01-01

    Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

  18. Suppression of Th2 immune responses by the sulfated polysaccharide from Porphyra haitanensis in tropomyosin-sensitized mice.

    Science.gov (United States)

    Shi, Chaolan; Pan, Tzuming; Cao, Minjie; Liu, Qingmei; Zhang, Lingjing; Liu, Guangming

    2015-02-01

    The sulfated polysaccharide from Porphyra was hypothesized to exhibit immunoregulatory, anti-tumor and anti-inflammatory activity, but its anti-allergic activity is not fully understood. Therefore, the aim of this study was to isolate sulfated polysaccharide from Porphyra haitanensis (PHPS) and investigate its anti-allergic potential using a tropomyosin (TM)-induced mouse allergy model. Intraperitoneal injection of PHPS suppressed the allergic reaction by modulating serum IgE, IgG1 and IgG2a levels in mice. In particular, when PHPS was injected prior to the first immunization with TM, the IgE level decreased by 34.2% compared with the control (PBS) group. Oral therapeutic administration of PHPS to TM-sensitized mice decreased histamine release and repaired the pathology in the jejunum of the small intestine. In vitro, the mRNA expressions of the TM-induced Th2 cytokines (interleukin-4 (IL-4), IL-5 and IL-13) in splenic lymphocytes were reduced by PHPS; however, the expression of Th1 and regulatory cytokines (interferon gamma (IFN-γ) and IL-10) were up-regulated in PHPS-treated splenic lymphocytes. In the splenic lymphocyte supernatant, the IL-4, IL-13 and IFN-γ levels were also regulated by PHPS. Moreover, PHPS induced IFN-γ secretion via the Jun N-terminal kinase (JNK) and Janus kinase 2 (JAK2) signaling pathways. Therefore, these results suggest that PHPS suppresses the TM-induced allergic reaction, possibly by modulating the imbalance of the Th1/Th2 immune response. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Gene expression of the concentration-sensitive sodium channel is suppressed in lipopolysaccharide-induced acute lung injury in mice.

    Science.gov (United States)

    Hagiwara, Teruki; Yoshida, Shigeru; Hidaka, Yuji

    2017-04-01

    The concentration-sensitive sodium channel (Na C ) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that Na C contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether Na C is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between Na C gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice. LPS-induced ALI mice were prepared by the intratracheal administration of LPS. Bronchoalveolar lavage (BAL) neutrophils and lung water content (LWCs) were used as a marker of ALI and pulmonary edema, respectively. Na C protein production in the lung was detected by immunoblotting and immunofluorescence. The gene expressions of Na C and the epithelial sodium channel (ENaC) of LPS-induced ALI mice were examined by quantitative RT-PCR over a time course of 14 days. The BAL neutrophil count increased until day 2 after LPS administration and had nearly recovered by day 6. LWCs in LPS-induced mice gradually increased until day 8 and had recovered by day 14. The expression of the Na C protein in the lungs of LPS-induced mice dramatically decreased from day 2 to day 6, but recovered by day 8. The mRNA expression of Na C decreased in the lung, as well as those for α-, β-, and γ-ENaC during ALI. Thus, Na C expression is suppressed during the development stage of pulmonary edema and then recovers in the convalescent phase. Our results suggest that suppression of the gene expression of Na C is involved in the development of pulmonary edema in ALI.

  20. Myeloid-specific Acat1 ablation attenuates inflammatory responses in macrophages, improves insulin sensitivity, and suppresses diet-induced obesity.

    Science.gov (United States)

    Huang, Li-Hao; Melton, Elaina M; Li, Haibo; Sohn, Paul; Jung, DaeYoung; Tsai, Ching-Yi; Ma, Tian; Sano, Hiroyuki; Ha, HyeKyung; Friedline, Randall H; Kim, Jason K; Usherwood, Edward; Chang, Catherine Cy; Chang, Ta-Yuan

    2018-03-13

    Macrophages are phagocytes that play important roles in health and diseases. Acyl-CoA:cholesterol acyltransferase 1 [ACAT1] converts cellular cholesterol to cholesteryl esters, and is expressed in many cell types. Unlike global Acat1 knockout [KO], myeloid-specific Acat1 KO [Acat1 -M/-M ] does not cause overt abnormalities in mice. Here we performed analyses in age and sex matched Acat1 -M/-M and wild-type mice on chow or Western diet, and discovered that Acat1 -M/-M mice exhibit resistance to Western diet-induced obesity. On both chow and Western diets, Acat1 -M/-M mice display decreased adipocyte size and increased insulin sensitivity. When.fed with Western diet, Acat1 -M/-M mice contain fewer infiltrating macrophages in white adipose tissue (WAT), with significantly diminished inflammatory phenotype. Without Acat1, the [Ly6C hi ] monocytes express reduced levels of integrin beta 1, which plays a key role in the interaction between monocytes and the inflamed endothelium. Adoptive transfer experiment showed that the appearance of leukocytes from Acat1 -M/-M mice to the inflamed WAT of WT mice is significantly diminished. Under Western diet, Acat1 -M/-M causes suppression of multiple pro-inflammatory genes in WAT. Cell culture experiments show that in Raw 264.7 macrophages, inhibiting ACAT1 with a small molecule ACAT1-specific inhibitor reduces inflammatory responses to lipopolysaccharide. We conclude that under Western diet, blocking ACAT1 in macrophages attenuates inflammation in WAT. Other results show that Acat1 -M/-M does not compromise anti-viral immune response. Our work reveals that blocking ACAT1 -M/-M suppresses diet-induced obesity in part by slowing down monocyte infiltration to WAT, as well as by reducing the inflammatory responses of adipose tissue macrophages.

  1. Increased sensitivity of CD4+ T-effector cells to CD4+CD25+ Treg suppression compensates for reduced Treg number in asymptomatic HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Georgina Thorborn

    Full Text Available BACKGROUND: In HIV infection, uncontrolled immune activation and disease progression is attributed to declining CD4+CD25+FoxP3+ regulatory T-cell (Treg numbers. However, qualitative aspects of Treg function in HIV infection, specifically the balance between Treg cell suppressive potency versus suppressibility of effector cells, remain poorly understood. This report addresses this issue. METHODOLOGY/PRINCIPAL FINDINGS: A classic suppression assay to measure CD4+CD45RO+CD25hi Treg cells to suppress the proliferation of CD4+CD45RO+CD25- effectors cells (E following CD3/CD28 polyclonal stimulation was employed to compare the suppressive ability of healthy volunteers (N = 27 and chronic, asymptomatic, treatment naïve, HIV-infected subjects (N = 14. HIV-infected subjects displayed significantly elevated Treg-mediated suppression compared to healthy volunteers (p = 0.0047. Cross-over studies comparing Treg cell potency from HIV-infected versus control subjects to suppress the proliferation of a given population of allogeneic effector cells demonstrated increased sensitivity of CD4+CD25- effector cells from HIV-infected subjects to be suppressed, associated with reduced production of the Treg counter-regulatory cytokine, IL-17, rather than an increase in the suppressive potential of their CD4+CD25+ Treg cells. However, compared to controls, HIV+ subjects had significantly fewer absolute numbers of circulating CD4+CD25+FoxP3+ Treg cells. In vitro studies highlighted that one mechanism for this loss could be the preferential infection of Treg cells by HIV. CONCLUSIONS/SIGNIFICANCE: Together, novel data is provided to support the contention that elevated Treg-mediated suppression may be a natural host response to HIV infection.

  2. 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.

  3. Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity.

    Science.gov (United States)

    Sun, Shuhong; Wang, Ran; Song, Jianwen; Guan, Ming; Li, Na; Zhang, Xiaotian; Zhao, Zhenwen; Zhang, Junjie

    2017-11-01

    Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine. Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Upregulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that glycoprotein 130 (gp130)-mediated Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) activation was required for abundant ATX expression in adipocytes. Through gp130, the interleukin 6 (IL-6) family cytokines, such as IL-6, leukemia inhibitory factor, cardiotrophin-1, and ciliary neurotrophic factor, upregulated ATX expression in adipocytes. ATX contributes to the induction of insulin resistance and lipolysis in IL-6-stimulated adipocytes. Oral administration of gp130 inhibitor SC144 suppressed ATX expression in adipose tissue, decreased plasma ATX, LPA, and FFA levels, and significantly improved insulin sensitivity and glucose tolerance in high-fat diet-fed obese mice. In summary, our results indicate that the activation of gp130-JAK-STAT3 pathway by IL-6 family cytokines has an important role in regulating ATX expression in adipocytes and that gp130 is a promising target in the management of obesity-associated glucose metabolic diseases. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    Directory of Open Access Journals (Sweden)

    Harris Peter S

    2012-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of

  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. Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression

    International Nuclear Information System (INIS)

    Paschall, Amy V; Bielawska, Alicja; Liu, Kebin; Zimmerman, Mary A; Torres, Christina M; Yang, Dafeng; Chen, May R; Li, Xia; Bieberich, Erhard; Bai, Aiping; Bielawski, Jacek

    2014-01-01

    Ceramide is a bioeffector that mediates various cellular processes, including apoptosis. However, the mechanism underlying ceramide function in apoptosis is apparently cell type-dependent and is not well-understood. We aimed at identifying molecular targets of ceramide in metastatic human colon and breast cancer cells, and determining the efficacy of ceramide analog in suppression of colon and breast cancer metastasis. The activity of and mechanism underlying ceramide as a cytotoxic agent, and as a sensitizer for Fas-mediated apoptosis was analyzed in human cell lines established from primary or metastatic colon and breast cancers. The efficacy of ceramide analog LCL85 in suppression of metastasis was examined in preclinical mouse tumor models. Exposure of human colon carcinoma cells to ceramide analog LCL85 results in apoptosis in a dose-dependent manner. Interestingly, a sublethal dose of LCL85 increased C16 ceramide content and overcame tumor cell resistance to Fas-mediated apoptosis. Subsequently, treatment of tumor cells with exogenous C16 ceramide resulted in increased tumor cell sensitivity to Fas-mediated apoptosis. LCL85 resembles Smac mimetic BV6 in sensitization of colon carcinoma cells to Fas-mediated apoptosis by inducing proteasomal degradation of cIAP1 and xIAP proteins. LCL85 also decreased xIAP1 and cIAP1 protein levels and sensitized metastatic human breast cancer cells to Fas-mediated apoptosis. Silencing xIAP and cIAP1 with specific siRNAs significantly increased the metastatic human colon carcinoma cell sensitivity to Fas-mediated apoptosis, suggesting that IAP proteins mediate apoptosis resistance in metastatic human colon carcinoma cells and ceramide induces IAP protein degradation to sensitize the tumor cells to apoptosis induction. Consistent with its apoptosis sensitization activity, subtoxic doses of LCL85 suppressed colon carcinoma cell metastatic potential in an experimental lung metastasis mouse model, as well as breast cancer growth

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    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/sub 4/), 29 patients with triiodothyronine (T/sub 3/). In 33/43 patients (77%) under T/sub 4/- and in 18/29 patients (62%) under T/sub 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.

  11. Blockade of Serotonin 5-HT2AReceptors Suppresses Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice.

    Science.gov (United States)

    Pang, Gang; Wu, Xian; Tao, Xinrong; Mao, Ruoying; Liu, Xueke; Zhang, Yong-Mei; Li, Guangwu; Stackman, Robert W; Dong, Liuyi; Zhang, Gongliang

    2016-01-01

    The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate - even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal. In this study, we examined the effect of blockade of 5-HT 2A receptors (5-HT 2A Rs) on morphine-induced behavioral sensitization and withdrawal in male mice. 5-HT 2A R antagonist MDL 11,939 (0.5 mg/kg, i.p.) suppressed acute morphine (5.0 mg/kg, s.c.)-induced increase in locomotor activity. Mice received morphine (10 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of morphine (10 mg/kg) was administered to induce the expression of behavioral sensitization. MDL 11,939 (0.5 mg/kg, i.p.) pretreatment suppressed the expression of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. MDL 11,939 (0.5 mg/kg, i.p.) prevented naloxone-precipitated withdrawal in morphine-dependent mice on day 7. Moreover, chronic morphine treatment increased 5-HT 2A R protein level and decreased the phosphorylation of extracellular signal-regulated kinases in the prefrontal cortex. Together, these results by the first time demonstrate that 5-HT 2A Rs modulate opioid dependence and blockade of 5-HT 2A R may represent a novel strategy for the treatment of morphine use disorders. (i)Blockade of 5-HT 2A receptors suppresses the expression of morphine-induced behavioral sensitization.(ii)Blockade of 5-HT 2A receptors suppresses naloxone-precipitated withdrawal in morphine-treated mice.(iii)Chronic morphine exposure induces an increase in 5-HT 2A receptor protein level and a decrease in ERK protein phosphorylation in prefrontal cortex.

  12. Panobinostat enhances cytarabine and daunorubicin sensitivities in AML cells through suppressing the expression of BRCA1, CHK1, and Rad51.

    Directory of Open Access Journals (Sweden)

    Chengzhi Xie

    Full Text Available Acute myeloid leukemia (AML remains a challenging disease to treat and urgently requires new therapies to improve its treatment outcome. In this study, we investigated the molecular mechanisms underlying the cooperative antileukemic activities of panobinostat and cytarabine or daunorubicin (DNR in AML cell lines and diagnostic blast samples in vitro and in vivo. Panobinostat suppressed expression of BRCA1, CHK1, and RAD51 in AML cells in a dose-dependent manner. Further, panobinostat significantly increased cytarabine- or DNR-induced DNA double-strand breaks and apoptosis, and abrogated S and/or G2/M cell cycle checkpoints. Analogous results were obtained by shRNA knockdown of BRCA1, CHK1, or RAD51. Cotreatment of NOD-SCID-IL2Rγ(null mice bearing AML xenografts with panobinostat and cytarabine significantly increased survival compared to either cytarabine or panobinostat treatment alone. Additional studies revealed that panobinostat suppressed the expression of BRCA1, CHK1, and RAD51 through downregulation of E2F1 transcription factor. Our results establish a novel mechanism underlying the cooperative antileukemic activities of these drug combinations in which panobinostat suppresses expression of BRCA1, CHK1, and RAD51 to enhance cytarabine and daunorubicin sensitivities in AML cells.

  13. Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut.

    Science.gov (United States)

    Dioszeghy, Vincent; Mondoulet, Lucie; Puteaux, Emilie; Dhelft, Véronique; Ligouis, Mélanie; Plaquet, Camille; Dupont, Christophe; Benhamou, Pierre-Henri

    2017-09-01

    Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show that although EPIT, OIT and SLIT were all able to effectively desensitize peanut-sensitized mice, they induced different subsets of Tregs. Foxp3+ Tregs were induced by the three treatment routes but with greater numbers induced by EPIT. EPIT and OIT also increased the level of LAP+ Tregs, whereas SLIT induced IL-10+ cells. The suppressive activity of EPIT-induced Tregs did not depend on IL-10 but required CTLA-4, whereas OIT acted through both mechanisms and SLIT was strictly dependent on IL-10. Moreover, the three routes influenced the homing properties of induced Tregs differently, with a larger repertoire of chemokine receptors expressed by EPIT-induced Tregs compared with OIT- and SLIT- induced cells, resulting in different protective consequences against allergen exposure. Furthermore, whereas OIT- or SLIT-induced Tregs lost their suppressive activities after treatment was discontinued, the suppressive activities of EPIT-induced Tregs were still effective 8 weeks after the end of treatment, suggesting the induction of a more long-lasting tolerance. In summary, EPIT, OIT and SLIT mediated desensitization through the induction of different subsets of Tregs, leading to important differences in the subsequent protection against allergen exposure and the possible induction of tolerance.

  14. A robust method for suppressing motion-induced coil sensitivity variations during prospective correction of head motion in fMRI.

    Science.gov (United States)

    Faraji-Dana, Zahra; Tam, Fred; Chen, J Jean; Graham, Simon J

    2016-10-01

    Prospective motion correction is a promising candidate solution to suppress the effects of head motion during fMRI, ideally allowing the imaging plane to remain fixed with respect to the moving head. Residual signal artifacts may remain, however, because head motion in relation to a fixed multi-channel receiver coil (with non-uniform sensitivity maps) can potentially introduce unwanted signal variations comparable to the weak fMRI BOLD signal (~1%-4% at 1.5-3.0T). The present work aimed to investigate the magnitude of these residual artifacts, and characterize the regime over which prospective motion correction benefits from adjusting sensitivity maps to reflect relative positional change between the head and the coil. Numerical simulations were used to inform human fMRI experiments. The simulations indicated that for axial imaging within a commonly used 12-channel head coil, 5° of head rotation in-plane produced artifact signal changes of ~3%. Subsequently, six young adults were imaged with and without overt head motions of approximately this extent, with and without prospective motion correction using the Prospective Acquisition CorrEction (PACE) method, and with and without sensitivity map adjustments. Sensitivity map adjustments combined with PACE strongly protected against the artifacts of interest, as indicated by comparing three metrics of data quality (number of activated voxels, Dice coefficient of activation overlap, temporal standard deviation of baseline fMRI timeseries data) across the different experimental conditions. It is concluded that head motion in relation to a fixed multi-channel coil can adversely affect fMRI with prospective motion correction, and that sensitivity map adjustment can mitigate this effect at 3.0T. Copyright © 2016 Elsevier Inc. All rights reserved.

  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. Late airway obstruction and neutrophil infiltration in sensitized mice after antigen provocation were suppressed by selective and non-selective phosphodiesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Osamu Kaminuma

    1997-01-01

    Full Text Available Suppression of antigen-induced late airway obstruction associated with neutrophilic inflammation by selective and non-selective phosphodiesterase (PDE inhibitors was investigated in mice. Respiratory resistance (Rrs increased in sensitized BDF1 mice 4-6 h after antigen provocation, whereas no obvious immediate reaction was observed. This reaction was associated with marked airway neutrophilia without significant infiltration of eosinophils. A selective PDE IV inhibitor, T-440 (10-30 mg/kg, and a non-selective PDE inhibitor, theophylline (10 mg/kg, significantly inhibited airway obstruction and neutrophilia when administered orally. An anti-allergic drug, ketotifen (1 mg/kg, caused slight inhibition of airway obstruction, whereas it did not affect airway neutrophilia. These results suggest that neutrophilic inflammation plays a role in the airway obstructive reaction and that PDE has a regulatory role in obstructive airway disease associated with airway inflammation.

  17. 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...... formatting in all three dimensions was possible to provide a comprehensive and exhaustive evaluation of the vessel wall. For the symptomatic carotid artery plaque, hyperintensive signal intensity was detected with a signal-to-noise ratio (SNR) that was significantly higher compared to the vessel wall...... proximal to the bifurcation (43.36±8.01 versus 16.91±3.49, respectively P plaque compared to the proximal carotid vessel wall was 26.45±4.60 and CNR plaque...

  18. 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

    Purpose/Introduction Atherosclerotic carotid artery disease is estimated to represent the etiology for one quarter of all strokes. Carotid cardiovascular magnetic resonance (CMR) and magnetic resonance angiography are promising tools in the evaluation of carotid atherosclerosis. Intraplaque...... 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...

  19. 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.

  20. NAC attenuates LPS-induced toxicity in aspirin-sensitized mouse macrophages via suppression of oxidative stress and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available Bacterial endotoxin lipopolysaccharide (LPS induces the production of inflammatory cytokines and reactive oxygen species (ROS under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC, an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.

  1. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep{sup ob/ob} mice

    Energy Technology Data Exchange (ETDEWEB)

    Sekiya, Motohiro [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Yahagi, Naoya, E-mail: nyahagi-tky@umin.ac.jp [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Laboratory of Molecular Physiology on Energy Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); 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 [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Yagyu, Hiroaki [Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi 329-0498 (Japan); Gotoda, Takanari [Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Nagai, Ryozo [Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Shimano, Hitoshi; Yamada, Nobuhiro [Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaragi 305-8575 (Japan); and others

    2009-09-25

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

  2. 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.

  3. miR-21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AKT pathway and improves paclitaxel sensitivity in cervical cancer cells.

    Science.gov (United States)

    Du, Guohui; Cao, Dongmei; Meng, Lingzheng

    2017-05-01

    The present study aimed to investigate the role and the molecular mechanisms underlying the effects of microRNA-21 (miR-21) on the proliferation, apoptosis and colony formation of cervical cancer cells, and to examine the role of miR-21 in mediating the sensitivity of cervical cancer cells to paclitaxel (PTX). Reverse transcription‑quantitative polymerase chain reaction was employed to determine the level of miR‑21 in various cervical cancer and normal cervical cells. The results revealed that the expression levels of miR-21 in cervical cancer cells were markedly higher when compared with normal cervical cells. Subsequently, a miR‑21 inhibitor or negative control (NC) was transfected into cervical cancer cells. Cell viability, colony formation and apoptosis were then analyzed using an MTT assay, crystal violet and Annexin V-fluorescein isothiocyanate/propidium iodide staining, respectively. The protein expression level of B-cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X (Bax), programmed cell death 4 (PDCD4), survivin, c‑myc, phosphatase and tensin homolog (PTEN) and phosphorylated (p)‑AKT were determined by western blot analysis. The sensitivity of cervical cancer cells to PTX (25, 50 and 100 µg/ml) was characterized using an MTT assay. The results demonstrated that the miR-21 inhibitor promoted apoptosis of cervical cancer cells and suppressed their proliferation and colony formation when compared with the NC. In addition, the expression levels of Bcl‑2, survivin, c‑myc and p‑AKT were significantly downregulated in cells transfected with the miR‑21 inhibitor, whilst the expression levels of Bax, PDCD4 and PTEN were significantly upregulated. Furthermore, the miR‑21 inhibitor significantly enhanced the inhibition efficacy of PTX at a range of concentrations in cervical cancer cells. It was concluded that inhibition of miR‑21 suppressed cell proliferation and colony formation through regulating the PTEN/AKT pathway, and improved PTX

  4. LH and testosterone production are more sensitive to the suppressive effects of food deprivation in prenatally undernourished male rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2015-06-01

    Although prenatal undernutrition affects the development of metabolic, physiological, and reproductive functions, it remains unclear whether it also affects physiological responses to undernutrition in adulthood. Therefore, in this study we examined whether prenatal undernutrition alters the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to fasting in adult male rats. The offspring of ad libitum fed dams (control) and ∼50% food-restricted (during the late gestational period) dams (IUGR) were sub-divided into ad libitum fed (fed) and 48 h food deprivation (FD) groups at 10 weeks of age. In each group, the serum levels of luteinizing hormone (LH), testosterone, and leptin and the hypothalamic mRNA expression levels of gonadotropin-releasing hormone (GnRH) regulatory factors were measured. The serum LH and testosterone levels of the IUGR-fed rats were significantly or tend to be higher than those of the control-fed rats, respectively. The serum LH levels of the IUGR-FD rats were lower than those of the IUGR-fed rats. Similarly, the serum testosterone levels of the IUGR-FD rats tended to be lower than those of the IUGR-fed rats. On the other hand, the serum LH and testosterone levels of the control-fed and control-FD rats did not differ. The serum leptin levels of the IUGR fed rats were higher than those of the control-fed rats. The serum leptin levels of the control-FD and IUGR-FD rats were lower than those of the control-fed and IUGR-fed rats, respectively. The hypothalamic neuropeptide Y (NPY) mRNA levels of the IUGR-FD rats were higher than those of the IUGR-fed rats. Similarly, hypothalamic NPY mRNA levels of control-FD rats were higher than those of the control-fed rats. The hypothalamic kisspeptin, kisspeptin receptor, RFamide-related peptide, GPR147, and OBRb mRNA levels of control fed rats did not differ between control-fed and IUGR-fed rats. Their mRNA levels of the fed and FD rats did not differ in the control or IUGR groups. These results

  5. 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

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    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.

  6. 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.

    Science.gov (United States)

    Mizuguchi, Hiroyuki; Das, Asish K; Maeyama, Kazutaka; Dev, Shrabanti; Shahriar, Masum; Kitamura, Yoshiaki; Takeda, Noriaki; Fukui, Hiroyuki

    2016-04-01

    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. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  7. 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.

  8. Characterization of capsaicin induced responses in mice vas deferens

    DEFF Research Database (Denmark)

    Sheykhzade, Majid; Gupta, Saurabh; Sørensen, Tinne

    2011-01-01

    -depth in isolated preparations. The present study sets out to study and characterize the capsaicin as well as CGRP-induced responses in isolated mouse vas deferens. The effects of capsaicin and CGRP family of peptides were studied on electrically-induced twitch responses in the absence or presence of transient...... receptor potential cation channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP family of peptides. The potency order was CGRP>intermedin-long (IMDL)~[Cys(Et)(2,7)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]a......CGRP>amylin (AMY). These responses were disinhibited by the CGRP receptor antagonists and TRPV1 antagonists. The addition of CGRP receptor antagonists caused a transient potentiation of the twitch response and this potentiation was blocked by pretreatment with capsaicin and enhanced by incubation with exogenous...

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

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    Qiyin Zhou

    Full Text Available 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. 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.

  11. 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

  12. 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.

  13. The C2 Protein from the Geminivirus Tomato Yellow Leaf Curl Sardinia Virus Decreases Sensitivity to Jasmonates and Suppresses Jasmonate-Mediated Defences.

    Science.gov (United States)

    Rosas-Díaz, Tábata; Macho, Alberto P; Beuzón, Carmen R; Lozano-Durán, Rosa; Bejarano, Eduardo R

    2016-01-15

    An increasing body of evidence points at a role of the plant hormones jasmonates (JAs) in determining the outcome of plant-virus interactions. Geminiviruses, small DNA viruses infecting a wide range of plant species worldwide, encode a multifunctional protein, C2, which is essential for full pathogenicity. The C2 protein has been shown to suppress the JA response, although the current view on the extent of this effect and the underlying molecular mechanisms is incomplete. In this work, we use a combination of exogenous hormone treatments, microarray analysis, and pathogen infections to analyze, in detail, the suppression of the JA response exerted by C2. Our results indicate that C2 specifically affects certain JA-induced responses, namely defence and secondary metabolism, and show that plants expressing C2 are more susceptible to pathogen attack. We propose a model in which C2 might interfere with the JA response at several levels.

  14. The C2 Protein from the Geminivirus Tomato Yellow Leaf Curl Sardinia Virus Decreases Sensitivity to Jasmonates and Suppresses Jasmonate-Mediated Defences

    Directory of Open Access Journals (Sweden)

    Tábata Rosas-Díaz

    2016-01-01

    Full Text Available An increasing body of evidence points at a role of the plant hormones jasmonates (JAs in determining the outcome of plant-virus interactions. Geminiviruses, small DNA viruses infecting a wide range of plant species worldwide, encode a multifunctional protein, C2, which is essential for full pathogenicity. The C2 protein has been shown to suppress the JA response, although the current view on the extent of this effect and the underlying molecular mechanisms is incomplete. In this work, we use a combination of exogenous hormone treatments, microarray analysis, and pathogen infections to analyze, in detail, the suppression of the JA response exerted by C2. Our results indicate that C2 specifically affects certain JA-induced responses, namely defence and secondary metabolism, and show that plants expressing C2 are more susceptible to pathogen attack. We propose a model in which C2 might interfere with the JA response at several levels.

  15. Reproducibility and utility of an overnight 0.25 mg dexamethasone suppression test as a marker for glucocorticoid sensitivity in children with asthma

    NARCIS (Netherlands)

    R.H. Willemsen (Ruben); L. van Leeuwen; T.A.S. Voorend-Van Bergen; Y.B. de Rijke (Yolanda); M.W.H. Pijnenburg (Mariëlle); E.L.T. van den Akker (Erica)

    2016-01-01

    textabstractPurpose: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment in children. However, there is considerable inter-individual variation in glucocorticoid sensitivity, leading to over- as well as undertreatment. A simple and fast test to predict glucocorticoid sensitivity

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

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    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%.

  17. 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%.

  18. Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test depend on suppression of lipolysis in type 2 diabetes: a randomised controlled trial.

    Science.gov (United States)

    Kahl, Sabine; Nowotny, Bettina; Piepel, Simon; Nowotny, Peter J; Strassburger, Klaus; Herder, Christian; Pacini, Giovanni; Roden, Michael

    2014-10-01

    The combined IVGTT-hyperinsulinaemic-euglycaemic clamp (Botnia clamp) allows the assessment of insulin secretion and sensitivity in one experiment. It remains unclear whether this clamp yields results comparable with those of the standard hyperinsulinaemic-euglycaemic clamp (SHEC) in diabetes patients. We hypothesised that the IVGTT induces responses affecting insulin sensitivity assessment. Of 22 randomised diet- or metformin-treated patients with well-controlled type 2 diabetes, 19 randomly underwent a Botnia clamp and an SHEC, spaced by 2 weeks, in one clinical research centre in a crossover study. The main outcomes were whole-body and hepatic insulin sensitivity as measured by the clamp and [6,6-(2)H2]glucose. Substrate utilisation was assessed from indirect calorimetry and beta cell function from insulin dynamics during IVGTT. The values of whole-body insulin sensitivity obtained from Botnia clamp and SHEC were correlated (r = 0.87, p clamp, but differed after IVGTT. The contribution of glucose oxidation to glucose disposal increased by 2.2 ± 0.3 and 1.2 ± 0.4 mg kg fat-free mass (FFM)(-1) min(-1) (Botnia and SHEC, p clamps correlated with individual variations of insulin sensitivity. The Botnia clamp provides similar estimates of insulin sensitivity as SHEC in patients with type 2 diabetes, but changes in NEFA during IVGTT may affect insulin sensitivity and thereby the discrimination between insulin-sensitive and insulin-resistant individuals. ClinicalTrials.gov NCT01397279 FUNDING: The study was funded by the Ministry of Science and Research of the State of North Rhine-Westphalia and the German Federal Ministry of Health, and supported in part by grants from the Federal Ministry for Research to the Centers for Diabetes Research, Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases and the Schmutzler-Stiftung.

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

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    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.

  20. Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.

    Science.gov (United States)

    Arum, Oge; Boparai, Ravneet K; Saleh, Jamal K; Wang, Feiya; Dirks, Angela L; Turner, Jeremy G; Kopchick, John J; Liu, Jun-Li; Khardori, Romesh K; Bartke, Andrzej

    2014-12-01

    In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1). The RIP::IGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-β-cell cell types. Multiple (nonsurvivorship) longevity-associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR-KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. Astragaloside IV Induced miR-134 Expression Reduces EMT and Increases Chemotherapeutic Sensitivity by Suppressing CREB1 Signaling in Colorectal Cancer Cell Line SW-480

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    Qi Ye

    2017-10-01

    Full Text Available Background: Colorectal cancer (CRC is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT plays critical role in the development of drug resistance. Aims: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. Methods: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. Results: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA chemotherapy. cAMP responsive element-binding protein 1 (CREB1, which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. Conclusions: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease.

  2. Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut

    OpenAIRE

    Dioszeghy, Vincent; Mondoulet, Lucie; Puteaux, Emilie; Dhelft, V?ronique; Ligouis, M?lanie; Plaquet, Camille; Dupont, Christophe; Benhamou, Pierre-Henri

    2016-01-01

    Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show ...

  3. Suppression of PC-1/PrLZ sensitizes prostate cancer cells to ionizing radiation by attenuating DNA damage repair and inducing autophagic cell death.

    Science.gov (United States)

    Shang, Zeng-Fu; Wei, Qiang; Yu, Lan; Huang, Fang; Xiao, Bei-Bei; Wang, Hongtao; Song, Man; Wang, Li; Zhou, Jianguang; Wang, Jian; Li, Shanhu

    2016-09-20

    Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity. Irradiation (IR) increased PC-1/PrLZ expression in a dose- and time-dependent manner and increased radiosensitivity in PC-1/PrLZ-suppressed cells was partially due to decreased DNA double strand break (DBS) repair which was measured with comet and gH2AX foci assays. Furthermore, depletion of PC-1/PrLZ impaired the IR-induced G2/M checkpoint, which has been reported to be correlate with radioresistance in cancer cells. PC-1/PrLZ-deficient cells exhibited higher level of autophagy when compared with control cells. Thus, specific inhibition of PC-1/PrLZ might provide a novel therapeutic strategy for radiosensitizing prostate cancer cells.

  4. Suppression chamber

    International Nuclear Information System (INIS)

    Goto, Hiroshi; Tsuji, Akio.

    1976-01-01

    Purpose: To miniaturize the storage tank of condensated water in BWR reactor. Constitution: A diaphragm is provided in a suppression chamber thereby to partition the same into an inner compartment and an outer compartment. In one of said compartments there is stored clean water to be used for feeding at the time of separating the reactor and for the core spray system, and in another compartment there is stored water necessary for accomplishing the depressurization effect at the time of coolant loss accident. To the compartment in which clean water is stored there is connected a water cleaning device for constantly maintaining water in clean state. As this cleaning device an already used fuel pool cleaning device can be utilized. Further, downcomers for accomplishing the depressurization function are provided in both inner compartment and outer compartment. The capacity of the storage tank can be reduced by the capacity of clean water within the suppression chamber. (Ikeda, J.)

  5. Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.

    Science.gov (United States)

    Mizuguchi, Hiroyuki; Hatano, Masaya; Matsushita, Chiyo; Umehara, Hayato; Kuroda, Wakana; Kitamura, Yoshiyuki; Takeda, Noriaki; Fukui, Hiroyuki

    2008-12-01

    Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.

  6. Cyclophosphamide chemotherapy sensitizes tumor cells to TRAIL-dependent CD8 T cell-mediated immune attack resulting in suppression of tumor growth.

    Directory of Open Access Journals (Sweden)

    Robbert G van der Most

    Full Text Available BACKGROUND: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. METHODS AND FINDINGS: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-alpha/beta response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-gamma and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5 antibodies. CONCLUSION: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion.

  7. 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

    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

  8. 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

  9. 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.

  10. Post-assembly atomic layer deposition of ultrathin metal-oxide coatings enhances the performance of an organic dye-sensitized solar cell by suppressing dye aggregation.

    Science.gov (United States)

    Son, Ho-Jin; Kim, Chul Hoon; Kim, Dong Wook; Jeong, Nak Cheon; Prasittichai, Chaiya; Luo, Langli; Wu, Jinsong; Farha, Omar K; Wasielewski, Michael R; Hupp, Joseph T

    2015-03-11

    Dye aggregation and concomitant reduction of dye excited-state lifetimes and electron-injection yields constitute a significant mechanism for diminution of light-to-electrical energy conversion efficiencies in many dye-sensitized solar cells (DSCs). For TiO2-based DSCs prepared with an archetypal donor-acceptor organic dye, (E)-2-cyano-3-(5'-(5''-(p-(diphenylamino)phenyl)-thiophen-2''-yl)thiophen-2'-yl)acrylic acid (OrgD), we find, in part via ultrafast spectroscopy measurements, that postdye-adsorption atomic layer deposition (ALD) of ultrathin layers of either TiO2 or Al2O3 effectively reverses residual aggregation. Notably, the ALD treatment is significantly more effective than the widely used aggregation-inhibiting coadsorbent, chenodeoxycholic acid. Primarily because of reversal of OrgD aggregation, and resulting improved injection yields, ALD post-treatment engenders a 30+% increase in overall energy conversion efficiency. A secondary contributor to increased currents and efficiencies is an ALD-induced attenuation of the rate of interception of injected electrons, resulting in slightly more efficient charge collection.

  11. 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

  12. Suppression of sympathetic detonation

    Science.gov (United States)

    Foster, J. C., Jr.; Gunger, M. E.; Craig, B. G.; Parsons, G. H.

    1984-08-01

    There are two basic approaches to suppression of sympathetic detonation. Minimizing the shock sensitivity of the explosive to long duration pressure will obviously reduce interround separation distances. However, given that the explosive sensitivity is fixed, then much can be gained through the use of simple barriers placed between the rounds. Researchers devised calculational methods for predicting shock transmission; experimental methods have been developed to characterize explosive shock sensitivity and observe the response of acceptors to barriers. It was shown that both EAK and tritonal can be initiated to detonation with relatively low pressure shocks of long durations. It was also shown that to be an effective barrier between the donor and acceptor, the material must attenuate shock and defect fragments. Future actions will concentrate on refining the design of barriers to minimize weight, volume, and cost.

  13. 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.

  14. Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling.

    Science.gov (United States)

    Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko; Kraljević Pavelić, Sandra; Lučin, Ksenija; Sedić, Mirela

    2017-06-10

    Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU and SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-07-01

    Full Text Available Abstract Protein kinases and phosphatases catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial signaling proteins in central nervous system. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. To explore the role of protein phosphatase in central sensitization of spinal nociceptive neurons following peripheral noxious stimulation, using electrophysiological recording techniques, we investigated the role of two inhibitors of protein phosphatase type 2A (PP2A, fostriecin and okadaic acid (OA, on the responses of dorsal horn neurons to mechanical stimuli in anesthetized rats following intradermal injection of capsaicin. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. A microdialysis fiber was implanted in the spinal cord dorsal horn for perfusion of ACSF and inhibitors of PP2A, fostriecin and okadaic acid. We found that in ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased over a period of 15 min after injection and had mostly recovered by 60 min later. However, pre- or post-treatment with the phosphatase inhibitors, fostriecin or OA, significantly enhanced the effects of capsaicin injection by prolonging the responses to more than 3 hours. These results confirm that blockade of protein phosphatase activity may potentiate central sensitization of nociceptive transmission in the spinal cord following capsaicin injection and indicate that protein phosphatase type 2A may be involved in determining the duration of capsaicin-induced central sensitization.

  16. IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses.

    Science.gov (United States)

    Auci, D L; Miller, H; Chice, S M; Durkin, H G

    1994-04-01

    The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses.

  17. Growth hormone suppression test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  18. 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.

  19. 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.

  20. γ-aminobutyric acid (GABA) oral rinse reduces capsaicin-induced burning mouth pain sensation

    DEFF Research Database (Denmark)

    Zhang, Yang; Wang, Kelun; Arendt-Nielsen, Lars

    2018-01-01

    BACKGROUND: In burning mouth patients, analgesia after oral administration of clonazepam may result from modulation of peripheral γ-aminobutyric acid (GABA) receptors. METHODS: The effect of oral administration of test solutions (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated...

  1. Effects of electroacupuncture on capsaicin-induced model of atopic dermatitis in rats.

    Science.gov (United States)

    Jung, Dal-Lim; Lee, Seung-Deok; Choi, In-Hwa; Na, Heung-Sik; Hong, Seung-Ug

    2014-04-01

    Electroacupuncture (EA) is used as a prescription to treat pruritus and atopic dermatitis. Whether EA affects experimental itch in rat models of immunologic or neuronal damages, however, is unknown. The present study was designed to determine the therapeutic effects of high-frequency EA on atopic dermatitis-like lesions in rats. Capsaicin (50mg/kg) was subcutaneously administered rat pups within 48h after birth. Rats then underwent 30min of EA at six acupoints (bilateral BL13, and unilateral LI11, ST36, SP10, SP6) every other day (EA group) for 3 weeks. Measurements of IgE, mast cells, scratching behavior, dynorphin release, skin thickness and dermatitis score were obtained. Only the dermatitis score and dynorphin expression were decreased in the EA group compared with the control non-EA group. We suggest that high-frequency EA alleviates pruritus of atopic dermatitis-like lesions in rats induced by capsaicin injection, via the release of dynorphin. These findings indicate a new potential therapeutic approach for the amelioration of symptoms of atopic dermatitis. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Dependence of nociceptive detection thresholds on physiological parameters and capsaicin-induced neuroplasticity: a computational study

    NARCIS (Netherlands)

    Yang, H.; Meijer, Hil Gaétan Ellart; Doll, Robert; Buitenweg, Jan R.; van Gils, Stephanus A.

    2016-01-01

    Physiological properties of peripheral and central nociceptive subsystems can be altered over time due to medical interventions. The effective change for the whole nociceptive system can be reflected in changes of psychophysical characteristics, e.g., detection thresholds. However, it is challenging

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

    DEFF Research Database (Denmark)

    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...

  4. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.

    Science.gov (United States)

    Romero, L; Zamanillo, D; Nadal, X; Sánchez-Arroyos, R; Rivera-Arconada, I; Dordal, A; Montero, A; Muro, A; Bura, A; Segalés, C; Laloya, M; Hernández, E; Portillo-Salido, E; Escriche, M; Codony, X; Encina, G; Burgueño, J; Merlos, M; Baeyens, J M; Giraldo, J; López-García, J A; Maldonado, R; Plata-Salamán, C R; Vela, J M

    2012-08-01

    The sigma-1 (σ(1) ) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ(1) receptor ligands used as pharmacological tools are unclear and the demonstration that σ(1) receptor antagonists have efficacy in reversing central sensitization-related pain sensitivity is still missing. The pharmacological properties of a novel σ(1) receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ(1) receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ(1) receptor occupancy were measured to substantiate behavioural data. Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of σ(1) receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve-injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ(1) receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. These findings contribute to evidence identifying the σ(1) receptor as a modulator of activity-induced spinal sensitization and pain hypersensitivity, and suggest σ(1) receptor antagonists as potential novel treatments for neuropathic pain. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  5. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

    Science.gov (United States)

    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; Tzeng, Yew-Min; Yeh, Chi-Tai

    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. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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....

  7. Pressure suppression device

    International Nuclear Information System (INIS)

    Ichiki, Tadaharu; Funahashi, Toshihiro.

    1976-01-01

    Purpose: To provide a structure which permits the absorption of shocks and vibratory load produced on the floor of a pressure suppression chamber due to nitrogen gas or the like discharged into pool water in the pressure suppression chamber at the time of a loss-of-coolant accident. Constitution: A pressure suppression chamber accommodating pool water is comprised of a bottom wall and side walls constructed of concrete on the inner side of a liner. By providing concrete on the bottom surface and side wall surfaces of a pressure suppression chamber, it is possible to prevent non-condensing gas and steam exhausted from the vent duct and exhaust duct of a main vapor escapement safety valve exhaust duct from exerting impact forces and vibratory forces upon the bottom and side surfaces of the pressure suppression chamber. (Horiuchi, T.)

  8. Position sensitive gaseous photomultipliers

    CERN Document Server

    Biteman, V; Peskov, Vladimir; Sakuraï, H; Silin, E; Sokolova, T; Radionov, I

    2001-01-01

    In this paper a simple design of a gaseous photomultiplier, sensitive up to visible light, is described. It consists of a parallel plate chamber combined with a solid photocathode through a capillary plate, which works in a transmission mode and serves to suppress photon feedback. Ion feedback was minimized through the optimization of the gas mixture. A gain >10 sup 3 was achieved.

  9. Charge Recombination Suppressed by Destructive Quantum Interference in Heterojunction Materials

    NARCIS (Netherlands)

    Tempelaar, Roel; Koster, L. Jan Anton; Havenith, Remco W. A.; Knoester, Jasper; Jansen, Thomas L. C.

    2016-01-01

    We show that charge recombination in ordered heterojunctions depends sensitively on the degree of coherent delocalization of charges at the donor acceptor interface. Depending on the relative sign of the electron and hole transfer integrals, such delocalization can dramatically suppress

  10. Menstrual suppression for adolescents.

    Science.gov (United States)

    Altshuler, Anna Lea; Hillard, Paula J Adams

    2014-10-01

    The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management. Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions. This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful.

  11. Cryogenic Acoustic Suppression Testing

    Data.gov (United States)

    National Aeronautics and Space Administration — A proof-of-concept method utilizing a cryogenic fluid for acoustic suppression in rocket engine testing environments will be demonstrated. It is hypothesized that...

  12. 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)

  13. 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

  14. Cardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicin.

    Science.gov (United States)

    Dutta, A; Deshpande, S B

    2010-09-01

    Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT(3) agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT(3) antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Bolus injection of PBG produced concentration-dependent (0.1-100 microg kg(-1)) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1-3 microg kg(-1)) and apnoea at higher concentrations (10-100 microg kg(-1)). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg(-1)) did not block the PBG-induced reflex responses. Capsaicin (0.1-10 microg kg(-1)), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin.

  15. 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.)

  16. 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

  17. Plasma suppression of beamstrahlung

    International Nuclear Information System (INIS)

    Whittum, D.H.; Sessler, A.M.; Stewart, J.J.; Yu, S.S.

    1988-06-01

    We investigate the use of a plasma at the interaction point of two colliding beams to suppress beamsstrahlung and related phenomena. We derive conditions for good current cancellation via plasma return currents and report on numerical simulations conducted to confirm our analytic results. 10 refs., 5 figs., 4 tabs

  18. 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

  19. 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

  20. How to suppress obsessive thoughts.

    Science.gov (United States)

    Rassin, Eric; Diepstraten, Philip

    2003-01-01

    Thought suppression (i.e. consciously trying to avoid certain thoughts from entering consciousness) has been argued to be an inadequate strategy in case of unwanted intrusions. That is, thought suppression seems to result in more rather than less intrusions. Although this experimental finding has been explained in terms of failing attempts to distract oneself from the target thought, the White Bear Suppression Inventory (WBSI; a scale that measures chronic thought suppression tendencies) does not address the means by which respondents try to suppress unwanted thoughts. To examine which strategies of mental control people use to suppress unwanted thoughts, obsessive-compulsive disorder patients (N=47) completed the WBSI, the Thought Control Questionnaire, and two measures of psychopathology. Results suggest that the crucial mechanism in thought suppression may not be distraction, but self-punishment.

  1. Unihemispheric burst suppression

    Directory of Open Access Journals (Sweden)

    Edward C. Mader Jr.

    2014-08-01

    Full Text Available Burst suppression (BS consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG. When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS.

  2. Growth Suppression and Therapy Sensitization of Breast Cancer

    Science.gov (United States)

    2001-07-01

    of Ad-p53 or Ad- Igal -infected cells, 48 hours post-infection, for the presence of oligonucleosomal fragments (Figure 4). These fragments are released...T98G parental 1-10-10(mutant) 1-10-6(mutant) T98GjJun i9gal p53 IRgal p53 Igal p53 Rgal p53 Figure 5. Western blot analysis of bax and bcl 2 protein...p n3easnse ta ine d usctionpof tolive takn fro mor i ce kileoa the nt telrination of thed-expeimentxpdesbdinTbl 1.or Nsectin cespohnd adtoite folloing

  3. Reverberation Suppression Using Wideband Doppler-Sensitive Pulses

    NARCIS (Netherlands)

    Doisy, Y; Deruaz, L.; IJsselmuide, S.P. van; Beerens, S.P.; Been, R.

    2008-01-01

    Abstract—The influence of transmitted waveforms on the signal-to-reverberation ratio (SRR) of a low-frequency active sonar is analyzed both theoretically and experimentally. Reverberation experiments have been conducted during a sea trial in a littoral water environment in October 1999. The aim of

  4. A cortical locus for anisotropic overlay suppression of stimuli presented at fixation.

    Science.gov (United States)

    Hansen, Bruce C; Richard, Bruno; Andres, Kristin; Johnson, Aaron P; Thompson, Benjamin; Essock, Edward A

    2015-01-01

    Human contrast sensitivity for narrowband Gabor targets is suppressed when superimposed on narrowband masks of the same spatial frequency and orientation (referred to as overlay suppression), with suppression being broadly tuned to orientation and spatial frequency. Numerous behavioral and neurophysiological experiments have suggested that overlay suppression originates from the initial lateral geniculate nucleus (LGN) inputs to V1, which is consistent with the broad tuning typically reported for overlay suppression. However, recent reports have shown narrowly tuned anisotropic overlay suppression when narrowband targets are masked by broadband noise. Consequently, researchers have argued for an additional form of overlay suppression that involves cortical contrast gain control processes. The current study sought to further explore this notion behaviorally using narrowband and broadband masks, along with a computational neural simulation of the hypothesized underlying gain control processes in cortex. Additionally, we employed transcranial direct current stimulation (tDCS) in order to test whether cortical processes are involved in driving narrowly tuned anisotropic suppression. The behavioral results yielded anisotropic overlay suppression for both broadband and narrowband masks and could be replicated with our computational neural simulation of anisotropic gain control. Further, the anisotropic form of overlay suppression could be directly modulated by tDCS, which would not be expected if the suppression was primarily subcortical in origin. Altogether, the results of the current study provide further evidence in support of an additional overlay suppression process that originates in cortex and show that this form of suppression is also observable with narrowband masks.

  5. Sensitivity analysis

    Science.gov (United States)

    ... this 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) ...

  6. 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.

  7. Assessment of Pain Response in Capsaicin-Induced Dynamic Mechanical Allodynia Using a Novel and Fully Automated Brushing Device

    Directory of Open Access Journals (Sweden)

    Kristian G du Jardin

    2013-01-01

    Full Text Available BACKGROUND: Dynamic mechanical allodynia is traditionally induced by manual brushing of the skin. Brushing force and speed have been shown to influence the intensity of brush-evoked pain. There are still limited data available with respect to the optimal stroke number, length, force, angle and speed. Therefore, an automated brushing device (ABD was developed, for which brushing angle and speed could be controlled to enable quantitative assessment of dynamic mechanical allodynia.

  8. 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.

  9. An Alternative to Thought Suppression?

    Science.gov (United States)

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  10. 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

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

    Science.gov (United States)

    Tran, Marie Thi Dao; Skovbjerg, Sine; Arendt-Nielsen, Lars; Christensen, Karl Bang; Elberling, Jesper

    2013-08-16

    Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. 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 a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes. In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month 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, immunological markers in serum, and quality of life. This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a documented effect on MCS, and in terms of

  12. 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

  13. Menstrual suppression in the adolescent.

    Science.gov (United States)

    Kantartzis, Kelly L; Sucato, Gina S

    2013-06-01

    Menstrual suppression, the use of contraceptive methods to eliminate or decrease the frequency of menses, is often prescribed for adolescents to treat menstrual disorders or to accommodate patient preference. For young women using hormonal contraceptives, there is no medical indication for menstruation to occur monthly, and various hormonal contraceptives can be used to decrease the frequency of menstruation with different side effect profiles and rates of amenorrhea. This article reviews the different modalities for menstrual suppression, common conditions in adolescents which may improve with menstrual suppression, and strategies for managing common side effects. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  14. 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...

  15. 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)

  16. 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

  17. In vivo Treg suppression assays.

    Science.gov (United States)

    Workman, Creg J; Collison, Lauren W; Bettini, Maria; Pillai, Meenu R; Rehg, Jerold E; Vignali, Dario A A

    2011-01-01

    To fully examine the functionality of a regulatory T cell (T(reg)) population, one needs to assess their ability to suppress in a variety of in vivo models. We describe five in vivo models that examine the suppressive capacity of T(regs) upon different target cell types. The advantages and disadvantages of each model including resources, time, and technical expertise required to execute each model are also described.

  18. In Vivo Treg Suppression Assays

    OpenAIRE

    Workman, Creg J.; Collison, Lauren W.; Bettini, Maria; Pillai, Meenu R.; Rehg, Jerold E.; Vignali, Dario A.A.

    2011-01-01

    To fully examine the functionality of a regulatory T cell (Treg) population, one needs to assess their ability to suppress in a variety of in vivo models. We describe five in vivo models that examine the suppressive capacity of Tregs upon different target cell types. The advantages and disadvantages of each model includ ing resources, time, and technical expertise required to execute each model are also described.

  19. Burst Suppression for ICP Control.

    Science.gov (United States)

    Zeiler, Frederick A; Akoth, Eva; Gillman, Lawrence M; West, Michael

    2017-02-01

    The goal of our study was to perform a systematic review of the literature to determine the effect that burst suppression has on intracranial pressure (ICP) control. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to January 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and the Grading of Recommendation Assessment Development and Education (GRADE) methodology. Seven articles were considered for review. A total of 108 patients were studied, all receiving burst suppression therapy. Two studies failed to document a decrease in ICP with burst suppression therapy. There were reports of severe hypotension and increased infection rates with barbiturate-based therapy. Etomidate-based suppressive therapy was linked to severe renal dysfunction. There currently exists both Oxford level 2b and GRADE C evidence to support that achieving burst suppression reduces ICP, and also has no effect on ICP, in severe traumatic brain injury. The literature suggests burst suppression therapy may be useful for ICP reduction in certain cases, although these situations are currently unclear. In addition, the impact on patient functional outcome is unclear. Further prospective study is warranted.

  20. 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.

  1. 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

  2. TRH Stimulation Tests Compared with T3 Suppression Tests in Patients With Marginal Hyperthyroidism

    International Nuclear Information System (INIS)

    Choi, Sung Jae; Koh, Chang Soon

    1980-01-01

    TRH stimulation tests and T 3 suppression tests were done in 13 patients with clinically suspected mild or early hyperthyroidism who were all conventional thyroid function tests gave results within the accepted normal range. The results were as follows 1) 6 patients with normal T 3 suppression test revealed normal TRH stimulation test and could be easily diagnosed as euthyroidism 2) 7 patients with abnormal T 3 suppression test exhibited no TSH response to TRH stimulation test and could be easily diagnosed as hyperthyroidism. The TRH stimulation test is a single, sensitive and reliable test of thyroid function and can well replace T 3 suppression test in the diagnosis of marginal hyperthyroidism

  3. Gluten Sensitivity

    Science.gov (United States)

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  4. 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

  5. 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

  6. Subjective Duration Distortions Mirror Neural Repetition Suppression

    Science.gov (United States)

    Pariyadath, Vani; Eagleman, David M.

    2012-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:23251340

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. Resonance suppression from color reconnection

    Science.gov (United States)

    Acconcia, R.; Chinellato, D. D.; de Souza, R. Derradi; Takahashi, J.; Torrieri, G.; Markert, C.

    2018-02-01

    We present studies that show how multi-parton interaction and color reconnection affect the hadro-chemistry in proton-proton (pp) collisions with special focus on the production of resonances using the pythia8 event generator. We find that color reconnection suppresses the relative production of meson resonances such as ρ0 and K* , providing an alternative explanation for the K*/K decrease observed in proton-proton collisions as a function of multiplicity by the ALICE collaboration. Detailed studies of the underlying mechanism causing meson resonance suppression indicate that color reconnection leads to shorter, less energetic strings whose fragmentation is less likely to produce more massive hadrons for a given quark content, therefore reducing ratios such as K*/K and ρ0/π in high-multiplicity pp collisions. In addition, we have also studied the effects of allowing string junctions to form and found that these may also contribute to resonance suppression.

  13. Teaching to suppress Polglish processes

    OpenAIRE

    Dziubalska-Kołaczyk, Katarzyna; Balas, Anna; Schwartz, Geoffrey; Rojczyk, Arkadiusz; Wrembel, Magdalena

    2015-01-01

    Advanced second language (henceforth L2) learners in a formal setting can suppress many first language (henceforth L1) processes in L2 pronunciation when provided with sufficient exposure to L2 and meta competence (see Sect. 4 for a definition of this term). This paper shows how imitation in L2 teaching can be enhanced on the basis of current phonetic research and how complex allophonic processes such as nasal vocalization and glottal stop insertion can be suppressed using “repair”—a method o...

  14. 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.

  15. Conditioned suppression, punishment, and aversion

    Science.gov (United States)

    Orme-Johnson, D. W.; Yarczower, M.

    1974-01-01

    The aversive action of visual stimuli was studied in two groups of pigeons which received response-contingent or noncontingent electric shocks in cages with translucent response keys. Presentation of grain for 3 sec, contingent on key pecking, was the visual stimulus associated with conditioned punishment or suppression. The responses of the pigeons in three different experiments are compared.

  16. Plasma suppression of beamstrahlung: Revision

    International Nuclear Information System (INIS)

    Whittum, D.H.; Sessler, A.M.; Stewart, J.J.; Yu, S.S.

    1988-06-01

    We investigate the use of a plasma at the interaction point of two colliding beams to suppress beamstrahlung and related phenomena. We derive conditions for good current cancellation via plasma return currents and report on numerical simulations conducted to confirm our analytic results. 17 refs., 5 figs., 5 tabs

  17. Partial dynamical symmetry and the suppression of chaos

    International Nuclear Information System (INIS)

    Whelan, N.; Alhassid, Y.; Leviatan, A.

    1993-01-01

    Partial dynamical symmetry is a situation in which the Hamiltonian does not have a certain symmetry yet a subset of its eigenstates does. It is shown that partial dynamical symmetry may cause suppression of chaos even in cases where the fraction of states which has the symmetry vanishes in the classical limit. The average entropy associated with the symmetry is a sensitive quantum measure of the partial symmetry and its effect on the chaotic dynamics

  18. Partial dynamical symmetry and the suppression of chaos

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, N.; Alhassid, Y. (Center for Theoretical Physics, Sloane Physics Laboratory, Yale University, New Haven, Connecticut 06511 (United States)); Leviatan, A. (Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel))

    1993-10-04

    Partial dynamical symmetry is a situation in which the Hamiltonian does not have a certain symmetry yet a subset of its eigenstates does. It is shown that partial dynamical symmetry may cause suppression of chaos even in cases where the fraction of states which has the symmetry vanishes in the classical limit. The average entropy associated with the symmetry is a sensitive quantum measure of the partial symmetry and its effect on the chaotic dynamics.

  19. 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

  20. 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.

  1. 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)

  2. Suppressing Quantum Fluctuations in Classicalization

    CERN Document Server

    Vikman, Alexander

    2013-01-01

    We study vacuum quantum fluctuations of simple Nambu-Goldstone bosons - derivatively coupled single scalar-field theories possessing shift-symmetry in field space. We argue that quantum fluctuations of the interacting field can be drastically suppressed with respect to the free-field case. Moreover, the power-spectrum of these fluctuations can soften to become red for sufficiently small scales. In quasiclassical approximation, we demonstrate that this suppression can only occur for those theories that admit such classical static backgrounds around which small perturbations propagate faster than light. Thus a quasiclassical softening of quantum fluctuations is only possible for theories which classicalize instead of having a usual Lorentz invariant and local Wilsonian UV- completion. We illustrate our analysis by estimating the quantum fluctuations for the DBI-like theories.

  3. Translating Cough Mechanisms Into Better Cough Suppressants.

    Science.gov (United States)

    Keller, Jennifer A; McGovern, Alice E; Mazzone, Stuart B

    2017-10-01

    Chronic cough is a significant problem, and in many patients cough remains refractive to both disease-specific therapies and current cough-suppressing medicines, creating a need for improved antitussive therapies. Most patients with chronic cough also display heightened sensitivity so that they experience a persistent sense of the need to cough, and often innocuous stimuli can trigger their coughing. This hypersensitivity underpins the newly described concept of cough hypersensitivity syndrome (CHS), a term that encapsulates the notion of common underlying mechanisms producing neuronal activation, sensitization and/or dysfunction, which are at the core of excessive coughing. Understanding these mechanisms has been a focus of recent research efforts in the field in the hope that new therapies can be developed to selectively target sensitized unproductive cough while maintaining the reflexive cough essential for airway protection. However, efforts to achieve this have been slower than expected, in part because of some significant challenges and limitations translating current cough models. In this review, we summarize recent advances in our understanding of the sensory circuits innervating the respiratory system that are important for cough, how cough sensory pathways become hypersensitive, and some of the recently described neural targets under development for treating chronic cough. We present the case that better use of current cough models or the development of new models, or both, is ultimately needed to advance our efforts to translate the discovery of basic cough mechanisms into effective medicines for treating patients with chronic cough. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. 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

  5. Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

    Science.gov (United States)

    Chen, Hua-Li; Liu, Yan; Jiang, Wei; Wang, Xiao-Xiao; Yuan, Guo-Lin; Zhao, Yi-Lin; Yu, Chao

    2018-03-05

    The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Sensitivity, Recalculated

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, J. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-07

    Prior to this study, the sensitivity in nEXO was calculated using an approximate method that does not provide 90% coverage. I find it useful to understand the confidence level of a limit by focusing on the confidence level as a property of the method used to find the limit.A particular method (algorithm,formula) is applied to an experiment to produce a limit. That experiment was conducted in a particular universe with certain values of the physical parameters. We’d like a method than produces a correct limit for 90% of the experiments that could run. We also want that to be true for every universe—that is, regardless of the physical parameter value, the method should still produce a correct limit 90% of the time.

  7. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    Science.gov (United States)

    Wang, Hong; Tollefson, Ann E.; Ying, Baoling; Korom, Maria; Cheng, Xiaohong; Cao, Feng; Davis, Katie L.; Wold, William S. M.

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family. PMID:25267681

  8. 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.

  9. Background Suppression Effects on Signal Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Burr, Tom [Los Alamos National Laboratory

    2008-01-01

    Gamma detectors at border crossings are intended to detect illicit nuclear material. One performance challenge involves the fact that vehicles suppress the natural background, thus potentially reducing detection probability for threat items. Methods to adjust for background suppression have been considered in related but different settings. Here, methods to adjust for background suppression are tested in the context of signal estimation. Adjustment methods include several clustering options. We find that for the small-to-moderate suppression magnitudes exhibited in the analyzed data, suppression adjustment is only moderatel helpful in locating the signal peak, and in estimating its width or magnitude.

  10. 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.)

  11. 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....

  12. 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.

  13. Nuclear reactor scram suppression device

    International Nuclear Information System (INIS)

    Koshi, Hiroshi; Ozawa, Hisamitsu.

    1993-01-01

    The device of the present invention suppresses reactor scram due to increase of neutrons caused by pressure elevation in the reactor even when a portion of main steam pipes is closed by some or other causes such as closure of a main steam isolation valve in a BWR type power plant. That is, when a flow channel is closed, such as upon closure of a main steam isolation valve, a flow rate signal sent from each of main steam flow rate detection means is inputted to a selective circuit of a pressure control device, from which a normal value is obtained. A deviation value for each of the main steam flow rate values is determined from the value described above and a flow rate average value obtained in an averaging circuit. Abnormality in the main steam pipelines is judged if a level for each of the deviation values is greater than a predetermined value. Further, the insertion of selective control rods and trip and run back instructions for recycling pumps are controlled by output signals of the deviation value detection circuit, to decrease the reactor power and prevent elevation in the reactor. As a result, reactor scram due to increase of neutron fluxes is suppressed. (I.S.)

  14. 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.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. Angiotensin II and taste sensitivity

    Directory of Open Access Journals (Sweden)

    Noriatsu Shigemura, DDS, PhD

    2015-05-01

    Full Text Available The sense of taste plays a major role in evaluating the quality of food components in the oral cavity. Sweet, salty, umami, sour and bitter taste are generally accepted as five basic taste qualities. Among them, salty taste is attractive to animals and influences sodium intake. Angiotensin II (ANG II and aldosterone (ALDO, which is stimulated by ANG II are key hormones that regulate sodium homeostasis and water balance. At the peripheral gustatory organs, it has been reported that ALDO increases the amiloride-sensitivity of the rat gustatory neural responses to NaCl in a time course of several hours. A recent study demonstrated that ANG II suppresses amiloride-sensitivity of the mouse gustatory and behavioral responses to NaCl via its receptor AT1 within an hour. Moreover, ANG II enhances sweet taste sensitivity without affecting umami, sour and bitter tastes. These results suggest that the reciprocal and sequential regulatory mechanisms by ANG II (as an acute suppressor together with ALDO (as a slow enhancer on the salt taste sensitivity may exist in peripheral taste organs, contribute to salt intake, and play an important role in sodium homeostasis. Furthermore, the linkage between salty and sweet taste modulations via the ANG II signaling may optimize sodium and calorie intakes.

  1. 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.

  2. 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.

  3. Photoperiodic suppression of drug reinstatement.

    Science.gov (United States)

    Sorg, B A; Stark, G; Sergeeva, A; Jansen, H T

    2011-03-10

    The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague-Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12 h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our

  4. 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.

  5. Menstrual suppression for adolescents with developmental disabilities.

    Science.gov (United States)

    Savasi, I; Spitzer, R F; Allen, L M; Ornstein, M P

    2009-06-01

    The approach to menstrual suppression for adolescents with developmental disabilities has evolved considerably over the years due to changing philosophies and evolving treatment options. We review the medical management options available for menstrual suppression with a focus on the needs and treatment of adolescents with developmental disabilities.

  6. Suppression of fertility in adult cats

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Wehrend, A.; Georgiev, P.

    2014-01-01

    and clinical options are available for the suppression of fertility in adult cats and the decision as to which should be chosen - independent of the legal registration of any state - depends on different facts: (i) feral or privately owned animal? (ii) temporary or permanent suppression of fertility wanted...

  7. Simulation analysis of a wildfire suppression system

    Science.gov (United States)

    Abílio Pereira Pacheco; João Claro; Tiago. Oliveira

    2013-01-01

    Rekindles and false alarms are unusually high in the Portuguese wildfire management system, representing a high burden on suppression resources in particular, and fire management resources in general. In 20,049 occurrences that the suppression system handled in the summer of 2010, 12.5% were false alarms and 15.0% were rekindles. We present a discreteevent simulation...

  8. 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

  9. Mu suppression as an index of sensorimotor contributions to speech processing: evidence from continuous EEG signals.

    Science.gov (United States)

    Cuellar, Megan; Bowers, Andrew; Harkrider, Ashley W; Wilson, Matthew; Saltuklaroglu, Tim

    2012-08-01

    Mu rhythm suppression is an index of sensorimotor activity during the processing of sensory stimuli. Two present studies investigate the extent to which this measure is sensitive to differences in acoustic processing. In both studies, participants were required to listen to 90second acoustic stimuli clips with their eyes closed and identify predetermined targets. Experimental conditions were designed to vary the acoustic processing demands. Mu suppression was measured continuously across central electrodes (C3, Cz, and C4). Ten adult females participated in the first study in which the target was a pseudoword presented in three conditions (identification, discrimination, discrimination in noise). Mu suppression was strongest and reached significance relative to baseline only in the discrimination in noise task at C3 (indicative of left hemisphere sensorimotor activity) when measured in a 10-12Hz bandwidth. Thirteen adult females participated in the second study, which measured mu suppression to acoustic stimuli with 'segmentation' (i.e., separating a parsed stimulus into individual components) versus non-segmentation requirements in both speech and tone discrimination conditions. Significantly greater overall suppression to speech relative to tone tasks was found in the 10-12Hz bandwidth. Further, suppression relative to baseline was significant only at C3 during the speech discrimination with segmentation task. Taken together, findings indicate that mu rhythm suppression in acoustic processing is sensitive to dorsal stream processing. More specifically, it is sensitive to (1) increases in overall processing demands and (2) processing linguistic versus non-linguistic information. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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

  12. Suppression of Aspergillus by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Jensen, Britt Guillaume; Jelsbak, Lars; Søndergaard, Ib

    Objectives: Cystic fibrosis patients are commonly infected by Pseudomonas aeruginosa, but Aspergilli are also frequently isolated. Our aim was to examine the possible interaction between P. aeruginosa and different Aspergillus. Methods: A suspension of 106 fungal spores/ml was streaked onto WATM......, here among 2-heptyl-3-hydroxy-4-quinolone (PQS). An unidentified green pseudomonas compound was also observed. Interestingly the P. aeruginosa mutant rpoN was unable to suppress A. fumigatus, but suppressed A. flavus, A. oryzae and A. niger. However several other P. aeruginosa mutants suppressed A....... fumigatus including flif, pilA, lasR, PVDA, PQSC and rhlA mutants indicating that phenazines may be involved in the suppressed growth of A. fumigatus. All pseudomonas mutants suppressed A. oryzae, A. niger and A. flavus. Conclusions: An increase in phenazine production by P. aeruginosa may contribute...

  13. Emotion suppression, not reappraisal, predicts psychotherapy outcome.

    Science.gov (United States)

    Scherer, Anne; Boecker, Maren; Pawelzik, Markus; Gauggel, Siegfried; Forkmann, Thomas

    2017-03-01

    The aim of this study was to identify whether trait emotion regulation strategies predict successful or unsuccessful psychotherapy outcomes in cognitive behaviour therapy. Three emotion regulation strategies (reappraisal, suppression, and externalizing behaviour) were assessed in 358 in- and outpatients. Patients were then grouped by therapy outcome. Emotion regulation strategies and confounding variables were entered as predictors in multinomial logistic regression analyses. Emotion suppression, but not reappraisal, was found to predict therapy outcomes for in- and outpatients, with patients high in suppression experiencing worse outcomes. Externalizing behaviour was only relevant in inpatient treatment. High suppression might be detrimental to psychotherapy outcome and should be assessed early on. Further research should investigate the influence of suppression on the mechanisms that facilitate change in psychotherapy.

  14. 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

  15. “Start” Mutants of Saccharomyces cerevisiae Are Suppressed in Carbon Catabolite-Derepressing Medium

    OpenAIRE

    Shuster, Jeffrey R.

    1982-01-01

    Temperature-sensitive cell division “start” mutants cdc28, cdc36, cdc37, and cdc39 of the yeast Saccharomyces cerevisiae arrested cell division in the G1 phase of the cell cycle in glucose medium. I report here that cdc28, cdc36, and cdc39 mutants were suppressed when grown in carbon catabolite-derepressing medium.

  16. Input-gain control produces feature-specific surround suppression.

    Science.gov (United States)

    Trott, Alexander R; Born, Richard T

    2015-03-25

    In primary visual cortex (V1), neuronal responses are sensitive to context. For example, responses to stimuli presented within the receptive field (RF) center are often suppressed by stimuli within the RF surround, and this suppression tends to be strongest when the center and surround stimuli match. We sought to identify the mechanism that gives rise to these properties of surround modulation. To do so, we exploited the stability of implanted multielectrode arrays to record from neurons in V1 of alert monkeys with multiple stimulus sets that more exhaustively probed center-surround interactions. We first replicated previous results concerning center-surround similarity using gratings representing all combinations of center and surround orientation. With this stimulus set, the surround simply scaled population responses to the center, such that the overall population tuning curve had the same shape and peak response. However, when the center contained two superimposed gratings (i.e., a visual "plaid"), one component of which always matched the surround orientation, suppression selectively affected the portion of the response driven by the matching center component, thereby producing shifts in the peak of the population orientation tuning curve. In effect, the surround caused neurons to respond predominantly to the component grating of the center plaid that was unmatched to the surround grating, as if by reducing the effective strength of whichever stimulus attributes were matched to the surround. These results provide key physiological support for theoretical models that propose feature-specific, input-gain control as the mechanism underlying surround suppression. Copyright © 2015 the authors 0270-6474/15/354973-10$15.00/0.

  17. 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.

  18. Rutin suppresses atopic dermatitis and allergic contact dermatitis.

    Science.gov (United States)

    Choi, Jin Kyeong; Kim, Sang-Hyun

    2013-04-01

    Atopic dermatitis (AD) and allergic contact dermatitis (ACD) is a common allergic inflammatory skin disease caused by a combination of eczematous, scratching, pruritus and cutaneous sensitization with allergens. The aim of our study was to examine whether rutin, a predominant flavonoid having anti-inflammatory and antioxidative potential, modulates AD and ACD symptoms. We established an atopic dermatitis model in BALB/c mice by repeated local exposure of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, 2,4-dinitroflourobenzene-sensitized a local lymph node assay was used for the ACD model. Repeated alternative treatment of DFE/DNCB caused AD symptoms. Topical application of rutin reduced AD based on ear thickness and histopathological analysis, in addition to serum IgE levels. Rutin inhibited mast cell infiltration into the ear and serum histamine level. Rutin suppressed DFE/DNCB-induced expression of interleukin (IL)-4, IL-5, IL-13, IL-31, IL-32 and interferon (INF)-γ in the tissue. In addition, rutin suppressed ACD based on ear thickness and lymphocyte proliferation, serum IgG2a levels, and expression of INF-γ, IL-4, IL-5, IL-10, IL-17 and tumour necrosis factor-α in ACD ears. This study demonstrates that rutin inhibits AD and ACD, suggesting that rutin might be a candidate for the treatment of allergic skin diseases.

  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. 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.

  2. 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.

  3. 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.)

  4. 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.

  5. Quadratic dynamical decoupling with nonuniform error suppression

    International Nuclear Information System (INIS)

    Quiroz, Gregory; Lidar, Daniel A.

    2011-01-01

    We analyze numerically the performance of the near-optimal quadratic dynamical decoupling (QDD) single-qubit decoherence errors suppression method [J. West et al., Phys. Rev. Lett. 104, 130501 (2010)]. The QDD sequence is formed by nesting two optimal Uhrig dynamical decoupling sequences for two orthogonal axes, comprising N 1 and N 2 pulses, respectively. Varying these numbers, we study the decoherence suppression properties of QDD directly by isolating the errors associated with each system basis operator present in the system-bath interaction Hamiltonian. Each individual error scales with the lowest order of the Dyson series, therefore immediately yielding the order of decoherence suppression. We show that the error suppression properties of QDD are dependent upon the parities of N 1 and N 2 , and near-optimal performance is achieved for general single-qubit interactions when N 1 =N 2 .

  6. 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.)

  7. Schistosoma mansoni-mediated suppression of allergic airway inflammation requires patency and Foxp3+ Treg cells.

    Directory of Open Access Journals (Sweden)

    Laura E Layland

    Full Text Available The continual rise of asthma in industrialised countries stands in strong contrast to the situation in developing lands. According to the modified Hygiene Hypothesis, helminths play a major role in suppressing bystander immune responses to allergens, and both epidemiological and experimental studies suggest that the tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus of this study was to investigate which developmental stages of schistosome infection confer suppression of allergic airway inflammation (AAI using ovalbumin (OVA as a model allergen. Moreover, we assessed the functional role and localization of infection-induced CD4(+Foxp3(+ regulatory T cells (Treg in mediating such suppressive effects. Therefore, AAI was elicited using OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was induced during various stages of infection, as well as after successful anti-helminthic treatment with praziquantel. The role of Treg was determined by specifically depleting Treg in a genetically modified mouse model (DEREG during schistosome infection. Alterations in AAI were determined by cell infiltration levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway hyper-sensitivity and lung pathology. Our results demonstrate that schistosome infection leads to a suppression of OVA-induced AAI when mice are challenged during the patent phase of infection: production of eggs by fecund female worms. Moreover, this ameliorating effect does not persist after anti-helminthic treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI responses. This is most likely due to a delayed reconstitution of Treg in infected-depleted animals which have strong ongoing immune responses. In summary, we conclude that schistosome-mediated suppression of AAI requires the presence of viable eggs and infection-driven Treg cells. These data provide evidence that helminth derived products

  8. A Computer Model of Saccadic Suppression.

    Science.gov (United States)

    1981-01-01

    Implications of sustained and transient channels for theories of visul pattern masking, saccadic suppression, and information processing...suppression. Because information available to the retina during saccades is a dynamic event in space and in time, the spatio-temporal properties of the...t), use is made of the convolution integral: In the context of the model, g(x,t) is the information supplied to a psychophysical detector and f(x,t

  9. Suppression mental questionnaire: a preliminary study

    OpenAIRE

    Salvatore Settineri; Emanuele Maria Merlo; Irene Pagano Dritto; Maria Midili; Antonio Bruno; Carmela Mento

    2016-01-01

    Authors postulate that the difference between suppression and repression, highlighted in particular by the Societè Psychanalitique de Paris, enables the development of a quantitative instrument, since suppression is a defense accessible to consciousness and therefore quantifiable like scales and questionnaires. The idea of constructing a questionnaire, included the identification of thirty variables having somehow a plausible relationship with this mechanism. The factor exploratory analysis w...

  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. Pressure suppression chamber for a reactor container

    International Nuclear Information System (INIS)

    Kato, Masami

    1980-01-01

    Purpose: To improve the safety of a pressure suppression device by floating shock absorbers on the surface of pressure suppression pool water in a pressure suppression chamber opposing to vent headers of a reactor container. Constitution: Vent pipes of a reactor container are provided with vent headers, vacuum valves which are actuated upon excessively high pressure resulted in the space of a pressure suppression chamber, and downcomers for supplying water, vapor, etc. from the container to the pressure suppression pool. Shock absorbers are floated on the surface of pool water opposing to the headers. Accordingly, if gaseous nitrogen or air sealed in the container is compressed upon loss of coolant accidents to rapidly form gas bubbles in the pool and thereby generate impact pressure to the pool water, the pressure are absorbed by the shock absorbers and not transmitted directly to the vent pies or headers, whereby the improved stability can be attained for the pressure suppression device of the reactor container. (Seki, T.)

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Suppression and ritualistic behaviour in normal participants.

    Science.gov (United States)

    Rassin, E; Merckelbach, H; Muris, P; Stapert, S

    1999-06-01

    Previous research has shown that normal and abnormal ritualistic behaviours do not differ in content. Rather, the differences between both categories of rituals pertain to characteristics such as frequency, intensity, discomfort and resistance. This study sought to investigate whether thought suppression is linked to these characteristics. Cross-sectional; questionnaires on thought suppression and rituals were administered to a sample of undergraduate students (N = 166). Habitual suppressors (N = 20) and non-suppressors (N = 20), as measured by the White Bear Suppression Inventory, were selected and compared with regard to the characteristics of their rituals. Suppressors experienced their rituals as more intense, discomforting and resistance-provoking than did non-suppressors. There were no group differences in the content, frequency, and perceived senselessness of rituals. Although the cross-sectional nature of the present study precludes causal inferences, its findings are consistent with the view that chronic thought suppression may promote ritualistic behaviour. Clearly, the details of the link between thought suppression and rituals require further examination.

  17. 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.

  18. 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.

  19. 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

  20. Post-translational suppression of expression of intestinal brush border enzymes by fructose

    DEFF Research Database (Denmark)

    Danielsen, E M

    1989-01-01

    The two major dietary sugars, fructose and sucrose, were found to suppress effectively the biosynthetic renewal of brush border enzymes in the gut. When studied in cultured explants of pig small intestine mucosa, 10-50 mM concentrations of fructose completely prevented the expression of mature...... aminopeptidase N and severely reduced that of sucrase-isomaltase. The instantly occurring and reversible suppressive effect manifested itself as a leupeptin-sensitive degradation of newly synthesized brush border enzymes. The likely mechanism of action of the dietary sugar is by causing an abnormal...... cotranslational glycosylation that in turn triggers a rapid proteolytic breakdown. Our findings suggest that renewal of digestive brush border enzymes is transiently suppressed during intake of fructose- or sucrose-rich meals....

  1. Type III intermittency: a nonlinear dynamic model of EEG burst suppression.

    Science.gov (United States)

    Rae-Grant, A D; Kim, Y W

    1994-01-01

    Burst suppression electroencephalograms from 9 comatose patients have been studied using nonlinear dynamic techniques. These EEG records show many dynamical features characteristic of nonlinear systems, including sensitive dependence on initial conditions, self-organization, similarity across scales, and intermittency. Histograms of burst durations showed an asymmetric distribution with a decreasing tail of increasing duration. Interpreting the histograms from the standpoint of intermittency classifications of iterated dynamical maps, the absence of any conspicuous maximal cut-off duration suggests a type III intermittency. The power-law exponent of the decreasing tail is -3/2 for type III intermittency in the large scale sample size limit, and we have found the EEGs to be consistent with type III intermittency behavior. We have also developed a nonlinear algorithm which models burst suppression pattern based on a low dimensional return map. Burst suppression pattern appears to be the constrained activity of a nonlinear dynamical system at the transition to chaos.

  2. Improved WATERGATE Pulse Sequences for Solvent Suppression in NMR Spectroscopy

    Science.gov (United States)

    Liu, Maili; Mao, Xi-an; Ye, Chaohui; Huang, He; Nicholson, Jeremy K.; Lindon, John C.

    1998-05-01

    Modifications to the WATERGATE method for removing the solvent resonance from1H NMR spectra are presented. In the conventional WATERGATE, a pulse train with three pairs of symmetric pulses in the form 3α-τ-9α-τ-19α-τ-19α-τ-9α-τ-3α (designated here W3), where 26α = 180°, is used, while the improved versions use four and five pairs of symmetric pulses (designated here W4 and W5), respectively. The modified methods provide narrower noninversion regions and hence enhance the sensitivities of the peaks close to the water resonance. The inversion and suppression profiles of the pulse trains W3, W4, and W5 are compared theoretically and experimentally and good agreement is obtained.

  3. Secondary Voltage Control for Harmonics Suppression in Islanded Microgrids

    DEFF Research Database (Denmark)

    Wang, Xiongfei; Guerrero, Josep M.; Blaabjerg, Frede

    2011-01-01

    This paper proposes a secondary voltage waveform control approach to suppress harmonics in islanded microgrids. Compared with the secondary control for traditional large power systems, the proposed control scheme can regulate the voltage waveform instead of voltage magnitude of sensitive buses...... in islanded microgrids. In addition to the centralized controller for fundamental frequency voltage component, a selective harmonic compensator is implemented in the secondary voltage control system. With the help of Park transformation, the cyclic references generated by the selective harmonic compensator...... passed through a low-bandwidth communication system to each primary control system for distributed generation units. Thus, combined with the high-bandwidth local voltage controllers in the primary control systems, harmonic voltage distortions in islanded microgrids are redistributed and reduced...

  4. 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.

  5. Modeling extreme ultraviolet suppression of electrostatic analyzers

    International Nuclear Information System (INIS)

    Gershman, Daniel J.; Zurbuchen, Thomas H.

    2010-01-01

    In addition to analyzing energy-per-charge ratios of incident ions, electrostatic analyzers (ESAs) for spaceborne time-of-flight mass spectrometers must also protect detectors from extreme ultraviolet (EUV) photons from the Sun. The required suppression rate often exceeds 1:10 7 and is generally established in tests upon instrument design and integration. This paper describes a novel technique to model the EUV suppression of ESAs using photon ray tracing integrated into SIMION, the most commonly used ion optics design software for such instruments. The paper compares simulation results with measurements taken from the ESA of the Mass instrument flying onboard the Wind spacecraft. This novel technique enables an active inclusion of EUV suppression requirements in the ESA design process. Furthermore, the simulation results also motivate design rules for such instruments.

  6. 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.

  7. 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.

  8. Star formation suppression in compact group galaxies

    DEFF Research Database (Denmark)

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

    2015-01-01

    We present CO(1-0) maps of 12 warm H-2-selected Hickson Compact Groups (HCGs), covering 14 individually imaged warm H2 bright galaxies, with the Combined Array for Research in Millimeter Astronomy. We found a variety of molecular gas distributions within the HCGs, including regularly rotating disks......, 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......-to-dust ratios of these galaxies to determine if an incorrect LCO-M(H2) conversion caused the apparent suppression and find that HCGs have normal gas-to-dust ratios. It is likely that the cause of the apparent suppression in these objects is associated with shocks injecting turbulence into the molecular gas...

  9. Weed suppression ability of spring barley varieties

    DEFF Research Database (Denmark)

    Christensen, Svend

    1995-01-01

    Three years of experiments with spring barley showed significant differences in weed suppression ability among varieties. Weed dry matter in the most suppressive variety, Ida, was 48% lower than the mean weed dry matter of all varieties, whereas it was 31% higher in the least suppressive variety......, Grit. Ranking varietal responses to weed competition in terms of grain yield loss corresponded well to ranking weed dry matter produced in crop weed mixtures. There was no correspondence between the varietal grain yields in pure stands and their competitiveness, suggesting that breeding to optimize...... interception model was developed to describe the light interception profiles of the varieties. A study of the estimated parameters showed significant correlation between weed dry matter, rate of canopy height development and the light interception profile. However, when estimates were standardized to eliminate...

  10. Male reproductive suppression: not a social affair.

    Science.gov (United States)

    Zizzari, Z Valentina; Jessen, Andrea; Koene, Joris M

    2017-10-01

    In the animal kingdom there are countless strategies via which males optimize their reproductive success when faced with male-male competition. These male strategies typically fall into two main categories: pre- and post-copulatory competition. Within these 2 categories, a set of behaviors, referred to as reproductive suppression, is known to cause inhibition of reproductive physiology and/or reproductive behavior in an otherwise fertile individual. What becomes evident when considering examples of reproductive suppression is that these strategies conventionally encompass reproductive interference strategies that occur between members of a hierarchical social group. However, mechanisms aimed at impairing a competitor's reproductive output are also present in non-social animals. Yet, current thinking emphasizes the importance of sociality as the primary driving force of reproductive suppression. Therefore, the question arises as to whether there is an actual difference between reproductive suppression strategies in social animals and equivalent pre-copulatory competition strategies in non-social animals. In this perspective paper we explore a broad taxonomic range of species whose individuals do not repeatedly interact with the same individuals in networks and yet, depress the fitness of rivals. Examples like alteration of male reproductive physiology, female mimicry, rival spermatophore destruction, and cementing the rival's genital region in non-social animals, highlight that male pre-copulatory reproductive suppression and male pre-copulatory competition overlap. Finally, we highlight that a distinction between male reproductive interference in animals with and without a social hierarchy might obscure important similarities and does not help to elucidate why different proximate mechanisms evolved. We therefore emphasize that male reproductive suppression need not be restricted to social animals.

  11. 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.

  12. Suppression mental questionnaire: a preliminary study

    Directory of Open Access Journals (Sweden)

    Salvatore Settineri

    2016-08-01

    Full Text Available Authors postulate that the difference between suppression and repression, highlighted in particular by the Societè Psychanalitique de Paris, enables the development of a quantitative instrument, since suppression is a defense accessible to consciousness and therefore quantifiable like scales and questionnaires. The idea of constructing a questionnaire, included the identification of thirty variables having somehow a plausible relationship with this mechanism. The factor exploratory analysis were identified three factors, named respectly “repressive function”,  “regression to the ego service” and “rationalization”, the first of which is the closest to the theoretical construct postulated.

  13. Feedback suppression in digital hearing instruments

    DEFF Research Database (Denmark)

    Ma, Guilin

    . Methods to extract the fixed model are proposed and proved to be effective in representing the invariant part of the feedback path. Based on the investigation of the dynamic changes of the feedback path in adverse situations, for example when the user picks up the telephone handset, a reflection model...... is developed as one type of the fast varying models. The techniques to suppress the feedback are then reviewed. To improve the existing feedback suppression systems, two approaches are proposed to address the so-called “bias problem”. The first approach improves the performance of the adaptive feedback...... of the proposed feedback path models in the feedback cancellation systems is presented....

  14. 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

  15. 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

  16. 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.

  17. Seizure Suppression by High Temperature via cAMP Modulation in Drosophila

    Science.gov (United States)

    Saras, Arunesh; Tanouye, Mark A.

    2016-01-01

    Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (parabss1, eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration. PMID:27558668

  18. 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.

  19. T2 relaxation measurement with solvent suppression and implications to solvent suppression in general.

    Science.gov (United States)

    Hoffmann, Markus M; Sobstyl, Hanna S; Badali, Vincent A

    2009-07-01

    A number of suppression pulse sequences including Excitation Sculpting and WATERGATE were incorporated into the standard Carr-Purcell-Meiboom-Gill (CPMG) program for T(2) measurement and experimentally evaluated. The chosen suppression schemes were of varying complexity encompassing pulse program elements, such as presaturation, gradients, and selective pulses, which are typically utilized for solvent suppression. The quality of the spectral data and the accuracy of T(2) measurements of the investigated suppression schemes were evaluated using three aqueous samples with increasing proton content in the water solvent, i.e. by volume 100% D(2)O, 80/20% D(2)O/H(2)O, and 20/80% D(2)O/H(2)O. For signals removed from the water signal, the T(2) values were generally very consistent between all pulse sequences tested. T(2) measurements can be unreliable for signals too close to the water signal such that they are significantly suppressed as well. Their intensity may actually grow initially through cross relaxation that transfers magnetization back to the solute signal. In turn, this relaxation phenomenon can be exploited to improve the spectral quality of conventional solvent suppression schemes. In favorable cases, even signals that are completely masked by the water signal can be recovered by adding a carefully chosen number of spin echoes with optimized evolution time to conventional water suppression pulse programs, such as Excitation Sculpting or WATERGATE. 2009 John Wiley & Sons, Ltd.

  20. Reappraising suppression: subjective and physiological correlates of experiential suppression in healthy adults

    Directory of Open Access Journals (Sweden)

    Mathieu eLemaire

    2014-06-01

    Full Text Available Background: Emotion regulation strategies based on suppressing behavioural expressions of emotion have been considered maladaptive. However this may not apply to suppressing the emotional experience (experiential suppression. The aim of this study was to define the effect of experiential suppression on subjective and physiological emotional responses. Methods: Healthy adults (N=101 were characterized in terms of the temperament, personality, and hedonic capacity using the Tridimensional Personality Questionnaire, the Eysenck Personality Questionnaire, the Fawcett-Clark Pleasure Scale and the State-Trait Anxiety Inventory. Participants were shown positive, negative and neutral pictures from the International Affective Picture System under two conditions, passive viewing and experiential suppression. During both conditions, subjective ratings of the intensity and duration of emotional responses and physiological measures of skin conductance (SC and cardiac inter-beat interval (IBI to each picture were recorded.Results: Negative pictures elicited the most intense physiological and emotional responses regardless of experimental condition. Ratings of emotional intensity were not affected by condition. In contrast, experiential suppression, compared to passive viewing, was associated with decreased duration of the emotional response, reduced maximum SC amplitude and longer IBIs independent of age, picture valence, personality traits, hedonic capacity and anxiety. Conclusion: These findings demonstrate that experiential suppression may represent an adaptive emotion regulation mechanism associated with reduced arousal and cardiovascular activation.

  1. Reappraising suppression: subjective and physiological correlates of experiential suppression in healthy adults.

    Science.gov (United States)

    Lemaire, Mathieu; El-Hage, Wissam; Frangou, Sophia

    2014-01-01

    Emotion regulation strategies based on suppressing behavioral expressions of emotion have been considered maladaptive. However, this may not apply to suppressing the emotional experience (experiential suppression). The aim of this study was to define the effect of experiential suppression on subjective and physiological emotional responses. Healthy adults (N = 101) were characterized in terms of the temperament, personality, and hedonic capacity using the Tridimensional Personality Questionnaire, the Eysenck Personality Questionnaire, the Fawcett-Clark Pleasure Scale, and the State-Trait Anxiety Inventory. Participants were shown positive, negative, and neutral pictures from the International Affective Picture System under two conditions, passive viewing, and experiential suppression. During both conditions, subjective ratings of the intensity and duration of emotional responses and physiological measures of skin conductance (SC) and cardiac inter-beat interval (IBI) to each picture were recorded. Negative pictures elicited the most intense physiological and emotional responses regardless of experimental condition. Ratings of emotional intensity were not affected by condition. In contrast, experiential suppression, compared to passive viewing, was associated with decreased duration of the emotional response, reduced maximum SC amplitude and longer IBIs independent of age, picture valence, personality traits, hedonic capacity, and anxiety. These findings demonstrate that experiential suppression may represent an adaptive emotion regulation mechanism associated with reduced arousal and cardiovascular activation.

  2. 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 ...

  3. Suppression of saccharin-induced mutagenicity by interferon-alpha in human RSa cells.

    Science.gov (United States)

    Suzuki, N; Suzuki, H

    1995-10-01

    Saccharin is an artificial sweetener commonly used in the formulation of foods and beverages. Sodium saccharin-induced mutagenicity is detectable in human RSa cells by estimation of cloning efficiency of ouabain-resistant mutant cells and determination of K-ras codon 12 mutation in genomic DNA, analyzed by PCR and differential dot-blot hybridization. However, in this study no phenotypic or genetic mutations were detected in RSa cells cultured with human IFN (HuIFN)-alpha before sodium saccharin treatment. The suppressive effect was lessened by transient treatment with antipain immediately after sodium saccharin treatment. Elevation of antipain-sensitive protease activity was found, furthermore, in RSa cells cultured with HuIFN-alpha and subsequently treated with sodium saccharin. Thus, antipain-sensitive protease induction in cells tested here may be involved in suppression of the mutagenicity of saccharin by HuIFN-alpha.

  4. 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.

  5. 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.

  6. Evaluation of nematode suppression and yield improvement ...

    African Journals Online (AJOL)

    SARAH

    2017-11-30

    Nov 30, 2017 ... Objective: To investigate nematode suppression and yield improvement potential of two organic materials; poultry manure ... region of Ghana. The organic materials were applied on two sweet potato varieties; Apomuden and Santom ..... but a trend similar to what happened in 2014 occurred at. Atebubu.

  7. Genetic sequences derived from suppression subtractive ...

    African Journals Online (AJOL)

    Leaf scald disease (LSD) is caused by the Gram-negative bacterium, Xanthomonas albilineans. Genomic DNA from X. albilineans and Xanthomonas hyacinthi were analyzed by suppression subtractive hybridization (SSH) using X. albilineans as the tester from which unique sequences were sought and X. hyacinthi as the ...

  8. 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.

  9. Suppression of Quantum Corrections by Classical Backgrounds

    CERN Document Server

    Brouzakis, Nikolaos

    2014-01-01

    We use heat-kernel techniques in order to compute the one-loop effective action in the cubic Galileon theory for a background that realizes the Vainshtein mechanism. We find that the UV divergences are suppressed relative to the predictions of standard perturbation theory at length scales below the Vainshtein radius.

  10. Emotions shape memory suppression in trait anxiety

    Directory of Open Access Journals (Sweden)

    Tessa eMarzi

    2014-01-01

    Full Text Available The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive and neutral, participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase, participants were again shown each word and asked to recall the paired scene. The results show that memory control is influenced by high trait anxiety and emotions. Low trait anxiety individuals showed a memory suppression effect, whereas there was a lack of memory suppression in high trait anxious individuals, especially for emotionally negative scenes. Thus, we suggest that individuals with anxiety may have difficulty exerting cognitive control over memories with a negative valence. These findings provide evidence that memory suppression can be impaired by anxiety thus highlighting the crucial relation between cognitive control, emotions and individual differences in regulating emotions.

  11. 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 ...

  12. Methanol Extract of Polyopes lancifolius Suppresses Tumor ...

    African Journals Online (AJOL)

    Results: The expression and activity of MMP-9 were significantly increased in response to TNF-α, but MEPL suppressed TNF-α-induced MMP-9 expression and activity. MEPL also inhibited TNF-α-induced MMP-9 expression at the transcriptional level by blocking the activation of the NF-κB signaling pathway. Furthermore ...

  13. Genetic sequences derived from suppression subtractive ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-17

    Jun 17, 2008 ... Genomic DNA from X. albilineans and Xanthomonas hyacinthi were analyzed by suppression subtractive ... Clone X. albilineans 12 showed 92% homology to the acetate repressor proteins and clone. X. albilineans 18 .... stranded DNA will be enriched for tester-specific DNA, as DNA fragments that are not ...

  14. Contour detection by surround suppression of texture

    NARCIS (Netherlands)

    Petkov, Nicolai; Tavares, JMRS; Jorge, RMN

    2007-01-01

    Based on a keynote lecture at Complmage 2006, Coimbra, Oct. 20-21, 2006, an overview is given of our activities in modelling and using surround inhibition for contour detection. The effect of suppression of a line or edge stimulus by similar surrounding stimuli is known from visual perception

  15. Are Patents used to Suppress Useful Technology?

    DEFF Research Database (Denmark)

    Howells, John

    2006-01-01

    suppression of innovation in the historical record (Dunford 1987; Merges and Nelson 1990). This paper shows that there are many errors of interpretation, both in the historical papers and in Dunford and Merges and Nelson's writing. Most important are confusions about the nature of technological competition...

  16. 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.

  17. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    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....... 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...... on the deliver of culturally sensitive care. Keywords: cultural sensitivity, nursing students, empirical research, report, interviews, study abroad programmes, phenomenology...

  18. Volcanic suppression of Nile summer flooding triggers revolt and constrains interstate conflict in ancient Egypt

    OpenAIRE

    Manning, Joseph G.; Ludlow, Francis; Stine, Alexander R.; Boos, William R.; Sigl, Michael; Marlon, Jennifer R.

    2017-01-01

    PUBLISHED 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 ...

  19. Molecular Characterization of Insulin-Mediated Suppression of Hepatic Glucose Production In Vivo

    OpenAIRE

    Ramnanan, Christopher J.; Edgerton, Dale S.; Rivera, Noelia; Irimia-Dominguez, Jose; Farmer, Ben; Neal, Doss W.; Lautz, Margaret; Donahue, E. Patrick; Meyer, Catalina M.; Roach, Peter J.; Cherrington, Alan D.

    2010-01-01

    OBJECTIVE Insulin-mediated suppression of hepatic glucose production (HGP) is associated with sensitive intracellular signaling and molecular inhibition of gluconeogenic (GNG) enzyme mRNA expression. We determined, for the first time, the time course and relevance (to metabolic flux) of these molecular events during physiological hyperinsulinemia in vivo in a large animal model. RESEARCH DESIGN AND METHODS 24 h fasted dogs were infused with somatostatin, while insulin (basal or 8× basal) and ...

  20. 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

  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. 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

  3. Coulomb suppression of the stellar enhancement factor

    International Nuclear Information System (INIS)

    Kiss, G.G.; Gyuerky, Gy.; Simon, A.; Fueloep, Zs.; Somorjai, E.

    2008-01-01

    Complete text of publication follows. Modern p process studies require large reaction networks, often including hundreds and thousands of nuclei and their respective reactions with light particles. Astrophysical reaction rates employed in reaction network calculations are determined either directly from cross sections or from the rate for the inverse reaction by applying detailed balance. The cross sections are known from experiment or predicted by theory. However, even when a reaction is experimentally accessible, often astrophysical rates cannot be directly measured. Excited states are thermally populated in an astrophysical plasma whereas only reactions on the ground state of the target can be investigated in the laboratory. A measure of the influence of the excited target states is given by the stellar enhancement factor f = r stellar /r g.s. , defined by the ratio of the stellar rate to the ground state rate. The enhancement factor f rev for the reverse reaction B(b,a)A (defined by having negative reaction Q value) is usually larger than the enhancement f forw of the forward reaction A(a,b)B (being the one with positive Q value) because more excited states are energetically accessible in nucleus B than in nucleus A. Therefore, it was assumed so far that more astrophysically relevant transitions are neglected when experimentally studying a reaction with negative Q value. However, there are cases for which f rev forw due to Coulomb suppression of a part of the energetically allowed transitions. This effect will be most pronounced in reactions with a charged particle in one and a neutral particle in the other channel, e.g. (n,p), but it can also appear when the entrance channel and exit channel have Coulomb barriers of different height, e.g. (p,α). Transitions from excited states to the same state in a compound nucleus are proceeding at smaller relative energy and are stronger suppressed by the Coulomb barrier. Thus, a prerequisite is that /Q/ is low compared to

  4. 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.

  5. Simulation of Suppression of Gamma Sensitivity of ‘Fission Electron-Collection’ Neutron Detector

    Science.gov (United States)

    Dong, Wang; Chuan-Fei, Zhang; Bo-Jun, Li; Yi-Ping, Cai; Xue-Bin, Zhu; Fen-Ni, Si; Zhi-Guo, Xi

    2016-05-01

    Not Available Supported by the National Natural Science Foundation of China under Grant No 11205141, and the Science and Technology Foundation of China Academy of Engineering Physics under Grant No 2012B0103003.

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

    Science.gov (United States)

    2005-06-01

    3-induced phos- Edman degradation. phorylation of bad through the protein kinase Akt. Science 278, 687-689 (1997). Modified manual Edman degradation...IL, E. Borrelli , and P. Chambon. 1985. Repression of the immunoglob- vation or TNF. On the other hand, Gas6 also can act as a ulin heavy chain...Nagata, K. 3. Borrelli , E., R. Hen, and P. Chambon. 1984. Adenovirus-2 ElA products Ohashi, K. Mizuno, and H. Arita. 1997. Cell adhesion to

  7. 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....

  8. 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...

  9. 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...

  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. 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.

  12. 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.

  13. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    Science.gov (United States)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  14. 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

  15. Suppression of friction by mechanical vibrations.

    Science.gov (United States)

    Capozza, Rosario; Vanossi, Andrea; Vezzani, Alessandro; Zapperi, Stefano

    2009-08-21

    Mechanical vibrations are known to affect frictional sliding and the associated stick-slip patterns causing sometimes a drastic reduction of the friction force. This issue is relevant for applications in nanotribology and to understand earthquake triggering by small dynamic perturbations. We study the dynamics of repulsive particles confined between a horizontally driven top plate and a vertically oscillating bottom plate. Our numerical results show a suppression of the high dissipative stick-slip regime in a well-defined range of frequencies that depends on the vibrating amplitude, the normal applied load, the system inertia and the damping constant. We propose a theoretical explanation of the numerical results and derive a phase diagram indicating the region of parameter space where friction is suppressed. Our results allow to define better strategies for the mechanical control of friction.

  16. 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.

  17. 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

  18. 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.

  19. Adaptive Suppression of Noise in Voice Communications

    Science.gov (United States)

    Kozel, David; DeVault, James A.; Birr, Richard B.

    2003-01-01

    A subsystem for the adaptive suppression of noise in a voice communication system effects a high level of reduction of noise that enters the system through microphones. The subsystem includes a digital signal processor (DSP) plus circuitry that implements voice-recognition and spectral- manipulation techniques. The development of the adaptive noise-suppression subsystem was prompted by the following considerations: During processing of the space shuttle at Kennedy Space Center, voice communications among test team members have been significantly impaired in several instances because some test participants have had to communicate from locations with high ambient noise levels. Ear protection for the personnel involved is commercially available and is used in such situations. However, commercially available noise-canceling microphones do not provide sufficient reduction of noise that enters through microphones and thus becomes transmitted on outbound communication links.

  20. Mechanisms underlying UV-induced immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, Stephen E. [Department of Immunology, University of Texas, MD Anderson Cancer Center, South Campus Research Building 1, 7455 Fannin St., P.O. Box 301402, Houston, TX 77030-1903 (United States)]. E-mail: sullrich@mdanderson.org

    2005-04-01

    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.

  1. Emotions shape memory suppression in trait anxiety

    OpenAIRE

    Marzi, Tessa; Regina, Antonio; Righi, Stefania

    2014-01-01

    The question that motivated this study was to investigate the relation between trait anxiety, emotions and memory control. To this aim, memory suppression was explored in high and low trait anxiety individuals with the Think/No-think paradigm. After learning associations between neutral words and emotional scenes (negative, positive, and neutral), participants were shown a word and were requested either to think about the associated scene or to block it out from mind. Finally, in a test phase...

  2. Currently available cough suppressants for chronic cough.

    Science.gov (United States)

    Chung, Kian Fan

    2008-01-01

    Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. Neural Networks for Mindfulness and Emotion Suppression.

    Directory of Open Access Journals (Sweden)

    Hiroki Murakami

    Full Text Available Mindfulness, an attentive non-judgmental focus on "here and now" experiences, has been incorporated into various cognitive behavioral therapy approaches and beneficial effects have been demonstrated. Recently, mindfulness has also been identified as a potentially effective emotion regulation strategy. On the other hand, emotion suppression, which refers to trying to avoid or escape from experiencing and being aware of one's own emotions, has been identified as a potentially maladaptive strategy. Previous studies suggest that both strategies can decrease affective responses to emotional stimuli. They would, however, be expected to provide regulation through different top-down modulation systems. The present study was aimed at elucidating the different neural systems underlying emotion regulation via mindfulness and emotion suppression approaches. Twenty-one healthy participants used the two types of strategy in response to emotional visual stimuli while functional magnetic resonance imaging was conducted. Both strategies attenuated amygdala responses to emotional triggers, but the pathways to regulation differed across the two. A mindful approach appears to regulate amygdala functioning via functional connectivity from the medial prefrontal cortex, while suppression uses connectivity with other regions, including the dorsolateral prefrontal cortex. Thus, the two types of emotion regulation recruit different top-down modulation processes localized at prefrontal areas. These different pathways are discussed.

  9. 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

  10. Echolocation versus echo suppression in humans

    Science.gov (United States)

    Wallmeier, Ludwig; Geßele, Nikodemus; Wiegrebe, Lutz

    2013-01-01

    Several studies have shown that blind humans can gather spatial information through echolocation. However, when localizing sound sources, the precedence effect suppresses spatial information of echoes, and thereby conflicts with effective echolocation. This study investigates the interaction of echolocation and echo suppression in terms of discrimination suppression in virtual acoustic space. In the ‘Listening’ experiment, sighted subjects discriminated between positions of a single sound source, the leading or the lagging of two sources, respectively. In the ‘Echolocation’ experiment, the sources were replaced by reflectors. Here, the same subjects evaluated echoes generated in real time from self-produced vocalizations and thereby discriminated between positions of a single reflector, the leading or the lagging of two reflectors, respectively. Two key results were observed. First, sighted subjects can learn to discriminate positions of reflective surfaces echo-acoustically with accuracy comparable to sound source discrimination. Second, in the Listening experiment, the presence of the leading source affected discrimination of lagging sources much more than vice versa. In the Echolocation experiment, however, the presence of both the lead and the lag strongly affected discrimination. These data show that the classically described asymmetry in the perception of leading and lagging sounds is strongly diminished in an echolocation task. Additional control experiments showed that the effect is owing to both the direct sound of the vocalization that precedes the echoes and owing to the fact that the subjects actively vocalize in the echolocation task. PMID:23986105

  11. Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hikaru; Nobeyama, Yoshimasa, E-mail: nobederm@jikei.ac.jp; Nakagawa, Hidemi

    2015-08-21

    Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. A proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated

  12. 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

    The authors calculate the sensitivities of micro four-point probe sheet resistance and Hall effect measurements to the local transport properties of nonuniform material samples. With in-line four-point probes, the measured dual configuration sheet resistance is more sensitive near the inner two...... 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...... is sensitive to both local carrier density and local carrier mobility because the position calculation is affected in the two pseudo-sheet-resistance measurements needed for the position error suppression. Furthermore, they have also simulated the sensitivity for the resistance difference Delta...

  13. 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)

  14. Dynamics of convulsive seizure termination and postictal generalized EEG suppression

    NARCIS (Netherlands)

    Bauer, P.R.; Thijs, R.D.; Lamberts, R.J.; Velis, D.N.; Visser, G.H.; Tolner, E.A.; Sander, J.W.; Lopes da Silva, F.H.; Kalitzin, S.N.

    It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression,

  15. Increased suppression of negative and positive emotions in major depression.

    Science.gov (United States)

    Beblo, Thomas; Fernando, Silvia; Klocke, Sabrina; Griepenstroh, Julia; Aschenbrenner, Steffen; Driessen, Martin

    2012-12-10

    Patients with major depression (MDD) show increased suppression of negative emotions. Emotion suppression is related to depressive symptoms such as depressive mood and anhedonia. It is not clear whether MDD patients also suppress positive emotions. In the present study we aim to investigate suppression of both negative and positive emotions in MDD patients as well as the relation between emotion suppression and depressive symptoms. In addition, we suggest that emotion suppression might be associated with fear of emotions. 39 MDD patients and 41 matched healthy control subjects were investigated for emotion suppression and fear of emotions with the Emotion Acceptance Questionnaire (EAQ). In addition, we applied additional questionnaires to validate emotion suppression findings and to assess depressive symptoms. MDD patients reported increased suppression of both negative and positive emotions. Suppression of negative and positive emotions was related to depressive symptoms. Patients also reported more fear of emotions than healthy subjects and this fear was related to emotion suppression in both study samples. Due to the cross-sectional and correlational study design, causal directions between the variables tested cannot be stated. Fear of emotion might be one reason why MDD patients suppress emotions. With regard to positive emotions, our results strongly suggest that therapeutic approaches should not only encourage patients to participate in potentially enjoyable situations but that patients may also benefit from practicing the allowance of pleasant emotions. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. 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...

  17. 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

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. Are Psychopaths Morally Sensitive?

    Science.gov (United States)

    Maxwell, Bruce; Le Sage, Leonie

    2009-01-01

    Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

  3. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    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......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...

  4. 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

  5. A smart dynamic vibration absorber for suppressing the vibration of a string supported by flexible beams

    Science.gov (United States)

    Nambu, Yohsuke; Yamamoto, Shota; Chiba, Masakatsu

    2014-02-01

    This study aims to effectively and robustly suppress the vibration of tension-stabilized structures (TSSs) using a smart dynamic vibration absorber (DVA). In recent years, a strong need has emerged for high-precision and high-functionality space structural systems for realizing advanced space missions. TSSs have attracted attention in this regard as large yet lightweight structural systems with high storage efficiency. A fundamental issue in the application of TSSs is vibration control of strings, of which TSSs are predominantly composed. In particular, the suppression of microvibrations is difficult because the deformation is almost perpendicular to the direction of vibration. A DVA is an effective device for suppressing microvibrations. However, the damping performance is sensitive to changes in dynamic properties. Furthermore, aging degradation and temperature dependence negatively affect DVA performance. This study aimed to develop a smart, active DVA with self-sensing actuation to improve robustness. A small cantilever with a piezoelectric transducer was utilized as a smart DVA. Numerical simulations and experiments showed that a passive DVA and the smart DVA suppressed vibrations but that the smart DVA showed improved effectiveness and robustness.

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-05

    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 /sup 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.

  8. 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

  9. 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

  10. Corticosteroid-induced suppression of in vitro lymphocyte proliferation in four captive rhinoceros species.

    Science.gov (United States)

    Roth, Terri L; Vance, Carrie K

    2007-12-01

    Captive African black rhinoceroses (Diceros bicornis) are unusually susceptible to several diseases not commonly observed in any of the other three rhinoceros species maintained in captivity. The potential role of corticosteroids (either endogenously produced or exogenously administered) in the development of these sometimes fatal diseases has been questioned. In this study, the suppressive effects of two therapeutic corticosteroids (dexamethasone and hydrocortisone) on in vitro lymphocyte proliferation was examined in four rhinoceros species, including the Sumatran rhinoceros (Dicerorhinus sumatrensis, n = 3), Indian rhinoceros (Rhinoceros unicornis, n = 4), African black rhinoceros (n = 10), and African white rhinoceros (Ceratotherium simum, n = 5). Three blood samples collected from each rhinoceros 1 mo to 1 yr apart provided replicates for the study. Both dexamethasone and hydrocortisone suppressed (P rhinoceros cell proliferation in response to any of the four mitogens was never completely suppressed, even in cultures containing the highest steroid concentration tested (10(-3) M). The effect of the two corticosteroids differed slightly among the rhinoceros species and subspecies tested, but there was no evidence that eastern or southern black rhinoceros lymphocytes were more sensitive to the suppressive effects of corticosteroids than the other rhinoceros species.

  11. Evidence for the suppressed decay B-→DK-, D→K+π-π0

    Science.gov (United States)

    Nayak, M.; Libby, J.; Trabelsi, K.; Adachi, I.; Aihara, H.; Asner, D. M.; Aushev, T.; Bakich, A. M.; Bala, A.; Behera, P.; Belous, K.; Bhardwaj, V.; Bonvicini, G.; Bozek, A.; Bračko, M.; Browder, T. E.; Červenkov, D.; Chang, M.-C.; Chang, P.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chistov, R.; Cho, I.-S.; Cho, K.; Chobanova, V.; Choi, Y.; Cinabro, D.; Dalseno, J.; Danilov, M.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Esen, S.; Farhat, H.; Fast, J. E.; Ferber, T.; Gaur, V.; Gabyshev, N.; Ganguly, S.; Gillard, R.; Goh, Y. M.; Golob, B.; Haba, J.; Hayashii, H.; Horii, Y.; Hoshi, Y.; Hou, W.-S.; Hyun, H. J.; Iijima, T.; Ishikawa, A.; Iwashita, T.; Jaegle, I.; Julius, T.; Kah, D. H.; Kato, E.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, M. J.; Kim, Y. J.; Kinoshita, K.; Klucar, J.; Ko, B. R.; Kodyš, P.; Korpar, S.; Krishnan, P.; Križan, P.; Krokovny, P.; Kuhr, T.; Kumita, T.; Kuzmin, A.; Kwon, Y.-J.; Lee, S.-H.; Li, J.; Li, Y.; Li Gioi, L.; Liu, Y.; Liventsev, D.; Lukin, P.; Miyake, H.; Mizuk, R.; Mohanty, G. B.; Moll, A.; Mori, T.; Muramatsu, N.; Mussa, R.; Nagasaka, Y.; Nakao, M.; Nedelkovska, E.; Negishi, K.; Ng, C.; Nisar, N. K.; Nitoh, O.; Ogawa, S.; Okuno, S.; Onuki, Y.; Pakhlov, P.; Pakhlova, G.; Park, C. W.; Park, H.; Pedlar, T. K.; Petrič, M.; Piilonen, L. E.; Ritter, M.; Röhrken, M.; Rostomyan, A.; Sahoo, H.; Saito, T.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Schwartz, A. J.; Senyo, K.; Seon, O.; Sevior, M. E.; Shapkin, M.; Shen, C. P.; Shibata, T.-A.; Shiu, J.-G.; Shwartz, B.; Sibidanov, A.; Simon, F.; Sohn, Y.-S.; Sokolov, A.; Solovieva, E.; Starič, M.; Steder, M.; Suzuki, Z.; Tamponi, U.; Tatishvili, G.; Teramoto, Y.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Vahsen, S. E.; Van Hulse, C.; Vanhoefer, P.; Varner, G.; Varvell, K. E.; Wagner, M. N.; Wang, C. H.; Wang, M.-Z.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamashita, Y.; Yashchenko, S.; Yusa, Y.; Zhilich, V.; Zhulanov, V.; Zupanc, A.

    2013-11-01

    We report a study of the suppressed decay B-→DK-, D→K+π-π0, where D denotes either a D0 or a D¯0 meson. The decay is sensitive to the CP -violating parameter ϕ3. Using a data sample of 772×106 BB¯ pairs collected at the Υ(4S) resonance with the Belle detector, we measure the ratio of branching fractions of the above suppressed decay to the favored decay B-→DK-, D→K-π+π0. Our result is RDK=[1.98±0.62(stat)±0.24(syst)]×10-2, which indicates the first evidence of the signal for this suppressed decay with a significance of 3.2 standard deviations. We measure the direct CP asymmetry between the suppressed B- and B+ decays to be ADK=0.41±0.30(stat)±0.05(syst). We also report measurements for the analogous quantities RDπ and ADπ for the decay B-→Dπ-, D→K+π-π0.

  12. Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium

    Directory of Open Access Journals (Sweden)

    Amara eGreer-Short

    2015-02-01

    Full Text Available Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL prolongation (overdrive suppression and RCL shortening (overdrive excitation. The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25±4.0%, n=10 without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C produced significantly earlier excited beats (53±14%, n=5 with wider QRS durations (58±6.3%, n=5 than suppressed beats. Digoxin + hypothermia (0.75 M produced the most excited beats with significantly earlier RCL (44±3.2%, n=6 and wider QRS (60±3.1%, n=6 ratios relative to suppressed beats. Increasing pacing further shortened RCL (30±7.8%, n=6. In a prospective study, TTX (100 nM increased RCL ratio (15±6.0%, n=10 without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.

  13. Post-translational suppression of expression of intestinal brush border enzymes by fructose

    DEFF Research Database (Denmark)

    Danielsen, E M

    1989-01-01

    The two major dietary sugars, fructose and sucrose, were found to suppress effectively the biosynthetic renewal of brush border enzymes in the gut. When studied in cultured explants of pig small intestine mucosa, 10-50 mM concentrations of fructose completely prevented the expression of mature am...... cotranslational glycosylation that in turn triggers a rapid proteolytic breakdown. Our findings suggest that renewal of digestive brush border enzymes is transiently suppressed during intake of fructose- or sucrose-rich meals.......The two major dietary sugars, fructose and sucrose, were found to suppress effectively the biosynthetic renewal of brush border enzymes in the gut. When studied in cultured explants of pig small intestine mucosa, 10-50 mM concentrations of fructose completely prevented the expression of mature...... aminopeptidase N and severely reduced that of sucrase-isomaltase. The instantly occurring and reversible suppressive effect manifested itself as a leupeptin-sensitive degradation of newly synthesized brush border enzymes. The likely mechanism of action of the dietary sugar is by causing an abnormal...

  14. 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.

  15. Mathematical modeling of continuous and intermittent androgen suppression for the treatment of advanced prostate cancer.

    Science.gov (United States)

    Voth, Alacia M; Alford, John G; Swim, Edward W

    2017-06-01

    Prostate cancer is one of the most prevalent types of cancer among men. It is stimulated by the androgens, or male sexual hormones, which circulate in the blood and diffuse into the tissue where they stimulate the prostate tumor to grow. One of the most important treatments for advanced prostate cancer has become androgen deprivation therapy (ADT). In this paper we present three different models of ADT for prostate cancer: continuous androgen suppression (CAS), intermittent androgen suppression (IAS), and periodic androgen suppression. Currently, many patients in the U.S. receive CAS therapy of ADT, but many undergo a relapse after several years and experience adverse side effects while receiving treatment. Some clinical studies have introduced various IAS regimens in order to delay the time to relapse, and/or to reduce the economic costs and adverse side effects. We will compute and analyze parameter sensitivity analysis for CAS and IAS which may give insight to plan effective data collection in a future clinical trial. Moreover, a periodic model for IAS is used to develop an analytical formulation for relapse times which then provides information about the sensitivity of relapse to the parameters in our models.

  16. 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).

  17. 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

  18. Silicon oxynitride: A field emission suppression coating

    Science.gov (United States)

    Theodore, Nimel D.

    We have studied coatings deposited using our inductively-coupled RF plasma ion implantation and desposition system to suppress field emission from large, 3-D electrode structures used in high voltage applications, like those used by Thomas Jefferson National Accelerator Facility in their DC-field photoelectron gun. Currently time and labor-intensive hand-polishing procedures are used to minimize field emission from these structures. Previous work had shown that the field emission from polished stainless steel (27 muA of field-emitted current at 15 MV/m) could be drastically reduced with simultaneous deposition of sputtered silicon dioxide during nitrogen implantation (167 pA of field-emitted current at 30 MV/m). We have determined that this unique implantation and deposition procedure produces high-purity silicon oxynitride films that can suppress field emission from stainless steel regardless of their initial surface polish. However, when this implantation procedure was applied to large, 3-D substrates, arcs occurred, damaging the coating and causing unreliable and unrepeatable field emission suppression. We have developed a novel reactive sputtering procedure to deposit high-purity silicon oxynitride coatings without nitrogen ion implantation. We can control the stoichometry and deposition rate of these coatings by adjusting the nitrogen pressure and incident RF-power. Using profilometry, Auger electron spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Rutherford backscattering spectrometry, elastic recoil detection analysis, and current-voltage measurements, we have determined that the elemental composition, chemical bonding, density, and electrical properties of the reactively-sputtered silicon oxynitride coatings are similar to those produced by nitrogen implantation during silicon dioxide deposition. Furthermore, high voltage tests determined that both coatings similarly suppress field emission from 6" diameter, polished

  19. 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 IAAs were markedly suppressed by rituximab in all patients for 1 year and for four patients as long as 3 years despite continuing insulin therapy. Independent of rituximab treatment, the mean level of IAAs at study entry was markedly lower (P = 0.035) for patients who maintained C-peptide levels during the first year of follow-up in both rituximab-treated and placebo groups. A single course of rituximab differentially suppresses IAAs, clearly blocking IAAs for >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.

  20. 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

  1. 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

  2. Constrained sensitivity theory

    International Nuclear Information System (INIS)

    Greenspan, E.; Williams, M.L.

    1980-01-01

    In sensitivity and uncertainty analysis of to-be-built reactors it is customary to use k-reset sensitivity functions - accounting for the combined effects of the change (or uncertainty) in the input data and of the alteration in some design variable applied to maintain criticality. Critical reactors are usually subjected to several constraints, such as power peaking factor and breeding ratio constraints, in addition to the criticality constraint. Perturbation theory formulations which can account, simultaneously, for several constraints both in critical reactors and in source driven systems (such as radiation shields and blankets of fusion devices) are presented. All the sensitivity and uncertainty analyses of source driven systems carried out so far used unconstrained sensitivity functions despite the fact that such systems can be also subjected to a variety of constraints

  3. 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...

  4. THE MOLECULAR BASIS OF SUPPRESSION IN AN OCHRE SUPPRESSOR STRAIN POSSESSING ALTERED RIBOSOMES*

    Science.gov (United States)

    Gartner, T. Kent; Orias, Eduardo; Lannan, James E.; Beeson, James; Reid, Parlane J.

    1969-01-01

    Escherichia coli K12 2320(λ)-15B has a mutation that results in ochre suppressor activity.1 This mutation concomitantly causes a decreased growth rate in rich medium, an increased sensitivity to streptomycin,1 and the production of some altered 30S ribosomes which are differentially sensitive to RNase.2 The results presented below demonstrate that the molecules which cause suppression are tRNA. These observations justify the conclusions that the suppressor mutation did not occur in a structural gene for a ribosomal component, and that the decreased growth rate in rich medium, the increased sensitivity to streptomycin, and the production of altered 30S ribosomes are probably all secondary consequences of the suppressor mutation. PMID:4895220

  5. 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.

  6. Radiation sensitivity of MOSFET

    International Nuclear Information System (INIS)

    Labrunee, M.; Tastet, P.; Garnier, J.

    1988-01-01

    Power MOS (Metal Oxide Semiconductor) transistors are widely used in Energy Conversion and radiation sensitivity is important for Space applications. After a review of the characteristics and applications of a MOSFET, we present the radiation tests (electrons flux exposure), and a synthesis about their heavy ions sensitivity). A simulation method of the radiation effect on the MOSFET behaviour used in a power converter is given. Design rules for on board systems using MOSFET are precised [fr

  7. COLOR- SENSITIZED SOLAR ELEMENTS

    OpenAIRE

    Gish R. A.; Ranabkhat K.; Yatsenko A. N.

    2016-01-01

    Photovoltaic devices are a promising solution to the energy crisis, because they generate electricity directly from sunlight, without producing CO2. While color-sensitized batteries are the most studied element, mainly due to its low cost and high efficiency solar energy conversion into electricity. Until recently, the color-sensitized solar cells performance was less than 1%, however, the use of titanium dioxide as the anode material have greatly raised their efficiency. The advantages of ti...

  8. 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...... data together with clinical data from metal workers heavily exposed to cobalt suggest that patch-test reactions are sometimes false positive and that patch testers should carefully evaluate their clinical relevance....

  9. 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.

  10. Suppressing drift chamber diffusion without magnetic field

    International Nuclear Information System (INIS)

    Martoff, C.J.; Snowden-Ifft, D.P.; Ohnuki, T.; Spooner, N.; Lehner, M.

    2000-01-01

    The spatial resolution in drift chamber detectors for ionizing radiation is limited by diffusion of the primary electrons. A strong magnetic field along the drift direction is often applied (Fancher et al., Nucl. Instr. and Meth. A 161 (1979) 383) because it suppresses the transverse diffusion, improving the resolution but at considerable increase in cost and complexity. Here we show that transverse track diffusion can be strongly suppressed without any magnetic field. This is achieved by using a gas additive which reversibly captures primary ionization electrons, forming negative ions. The ions drift with thermal energies even at very high drift fields and low pressures (E/P=28.5 V/cm torr), and the diffusion decreases with increasing drift field. Upon arrival at the avalanche region of the chamber the negative ions are efficiently stripped and ordinary avalanche gain is obtained. Using this technique, r.m.s. transverse diffusion less than 200 μm has been achieved over a 15 cm drift path at 40 torr with zero magnetic field. The method can provide high spatial resolution in detectors with long drift distances and zero magnetic field. Negative ion drift chambers would be particularly useful at low pressures and in situations such as space-based or underground experiments where detector size scaleability is important and cost, space, or power constraints preclude the use of a magnetic field

  11. Suppressing drift chamber diffusion without magnetic field

    CERN Document Server

    Martoff, C J; Ohnuki, T; Spooner, N J C; Lehner, M

    2000-01-01

    The spatial resolution in drift chamber detectors for ionizing radiation is limited by diffusion of the primary electrons. A strong magnetic field along the drift direction is often applied (Fancher et al., Nucl. Instr. and Meth. A 161 (1979) 383) because it suppresses the transverse diffusion, improving the resolution but at considerable increase in cost and complexity. Here we show that transverse track diffusion can be strongly suppressed without any magnetic field. This is achieved by using a gas additive which reversibly captures primary ionization electrons, forming negative ions. The ions drift with thermal energies even at very high drift fields and low pressures (E/P=28.5 V/cm torr), and the diffusion decreases with increasing drift field. Upon arrival at the avalanche region of the chamber the negative ions are efficiently stripped and ordinary avalanche gain is obtained. Using this technique, r.m.s. transverse diffusion less than 200 mu m has been achieved over a 15 cm drift path at 40 torr with ze...

  12. 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.

  13. Inhibition of SIRT2 suppresses hepatic fibrosis.

    Science.gov (United States)

    Arteaga, Maribel; Shang, Na; Ding, Xianzhong; Yong, Sherri; Cotler, Scott J; Denning, Mitchell F; Shimamura, Takashi; Breslin, Peter; Lüscher, Bernhard; Qiu, Wei

    2016-06-01

    Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis. Copyright © 2016 the American Physiological Society.

  14. 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...

  15. Lipopolysaccharide suppresses IgE-mast cell-mediated reactions.

    Science.gov (United States)

    Wang, N; McKell, M; Dang, A; Yamani, A; Waggoner, L; Vanoni, S; Noah, T; Wu, D; Kordowski, A; Köhl, J; Hoebe, K; Divanovic, S; Hogan, S P

    2017-12-01

    Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis. We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice. C57BL/6 WT, tlr4 -/- and IL10 -/- mice were exposed to LPS, and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE, and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca 2+ -mobilization and the expression of FcεRI on peritoneal MCs were quantitated. We show that LPS exposure of C57BL/6 WT mice constraints IgE-MC-mediated reactions. LPS-induced suppression of IgE-MC-mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression. Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10 pathway may be used as a therapeutic approach to prevent adverse IgE-mediated reactions. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Matsubara, Ryota; Kumagai, Kenichi; Shigematsu, Hiroaki; Kitaura, Kazutaka; Nakasone, Yasunari; Suzuki, Satsuki; Hamada, Yoshiki; Suzuki, Ryuji

    2017-06-25

    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.

  17. 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.

  18. 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

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

    Science.gov (United States)

    Arnold, Amy C; Diz, Debra I

    2014-12-01

    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. Copyright © 2014 the American Physiological Society.

  20. 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...

  1. Test results of lithium pool-air reaction suppression systems

    International Nuclear Information System (INIS)

    Jeppson, D.W.

    1987-02-01

    Engineered reaction suppression systems were demonstrated to be effective in suppressing lithium pool-air reactions for lithium quantities up to 100 kg. Lithium pool-air reaction suppression system tests were conducted to evaluate suppression system effectiveness for potential use in fusion facilities in mitigating consequences of postulated lithium spills. Small-scale perforated and sacrificial cover plate suppression systems with delayed inert gas purging proved effective in controlling the lithium-air interaction for lithium quantities near 15 kg at initial temperatures up to 450 0 C. A large-scale suppression system with a sacrificial cover, a diverter plate, an inert gas atmosphere, and remotely retrievable catch pans proved effective in controlling lithium pool-air interaction for a 100-kg lithium discharge at an initial temperature of 550 0 C. This suppression system limited the maximum pool temperature to about 600 0 C less than that expected for a similar lithium pool-air reaction without a suppression system. Lithium aerosol release from this large-scale suppression system was a factor of about 10,000 less than that expected for a lithium pool-air reaction with no suppression system. Remote retrieval techniques for lithium cleanup, such as (1) in-place lithium siphoning and overhead crane dismantling, and (2) lithium catch pan removal by use of an overhead crane, were demonstrated as part of this large-scale test

  2. Brassicaceous Seed Meals as Soil Amendments to Suppress the Plant-parasitic Nematodes Pratylenchus penetrans and Meloidogyne incognita1

    Science.gov (United States)

    Meyer, S. L. F.; Morra, M. J.

    2009-01-01

    Brassicaceous seed meals are the residual materials remaining after the extraction of oil from seeds; these seed meals contain glucosinolates that potentially degrade to nematotoxic compounds upon incorporation into soil. This study compared the nematode-suppressive ability of four seed meals obtained from Brassica juncea ‘Pacific Gold’, B. napus ‘Dwarf Essex’ and ‘Sunrise’, and Sinapis alba ‘IdaGold’, against mixed stages of Pratylenchus penetrans and Meloidogyne incognita second-stage juveniles (J2). The brassicaceous seed meals were applied to soil in laboratory assays at rates ranging from 0.5 to 10.0% dry w/w with a nonamended control included. Nematode mortality was assessed after 3 days of exposure and calculated as percentage reduction compared to a nonamended control. Across seed meals, M. incognita J2 were more sensitive to the brassicaceous seed meals compared to mixed stages of P. penetrans. Brassica juncea was the most nematode-suppressive seed meal with rates as low as 0.06% resulting in > 90% suppression of both plant-parasitic nematodes. In general B. napus ‘Sunrise’ was the least nematode-suppressive seed meal. Intermediate were the seed meals of S. alba and B. napus ‘Dwarf Essex’; 90% suppression was achieved at 1.0% and 5.0% S. alba and 0.25% and 2.5% B. napus ‘Dwarf Essex’, for M. incognita and P. penetrans, respectively. For B. juncea, seed meal glucosinolate-degradation products appeared to be responsible for nematode suppression; deactivated seed meal (wetted and heated at 70 °C for 48 hr) did not result in similar P. penetrans suppression compared to active seed meal. Sinapis alba seed meal particle size also played a role in nematode suppression with ground meal resulting in 93% suppression of P. penetrans compared with 37 to 46% suppression by pelletized S. alba seed meal. This study demonstrates that all seed meals are not equally suppressive to nematodes and that care should be taken when selecting a source

  3. Platelets Play a Central Role in Sensitization to Allergen.

    Science.gov (United States)

    Amison, Richard T; Cleary, Simon; Riffo-Vasquez, Yanira; Bajwa, Maidda; Page, Clive P; Pitchford, Simon C

    2018-01-24

    Platelet activation occurs in patients with allergic inflammation, and platelets can be activated directly by allergen via an IgE-dependent process. Platelets activate antigen-presenting cells (APCs) such as CD11c+ dendritic cells (DCs) in vitro. Whilst CD11c+ DCs are requisite for allergen sensitization, the role of platelets in this process is unknown. We investigated whether platelets were necessary for allergen sensitization. Balb/c mice sensitised to ovalbumin (OVA), were exposed to subsequent aerosolized allergen (OVA challenge). We analysed lung CD11c+ cell activation, co-localization with platelets, and some other indices of inflammation. The role of platelets at the time of allergen sensitization was assessed through platelet depletion experiments restricted to the period of sensitization. Platelets co-localized with airway CD11c+ cells, and this association increased after allergen sensitization, and after subsequent allergen exposure. Temporary platelet depletion (>95%) at the time of allergen sensitization led to a suppression of IgE and IL-4 synthesis, and a decrease in the pulmonary recruitment of eosinophils, macrophages, and lymphocytes after subsequent allergen exposure. Furthermore, in mice previously depleted of platelets at the time of sensitization, the recovered platelet population were shown to have reduced expression of FcɛRI. Pulmonary CD11c+ cell recruitment was suppressed in these mice after allergen challenge, suggesting the migration of CD11c+ cells in vivo may be dependent on direct platelet recognition of allergen. Platelets are necessary for efficient host sensitization to allergen. This propagates the subsequent inflammatory response during secondary allergen exposure, and increases platelet association with airway CD11c+ cells.

  4. 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

  5. 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.

  6. Stress and odor sensitivity in persons with noise sensitivity.

    Science.gov (United States)

    Nordin, Steven; Ljungberg, Jessica Korning; Claeson, Anna-Sara; Neely, Gregory

    2013-01-01

    Previous research has indicated that sensory sensitivity/intolerance to a specific modality may be part of a more general environmental hypersensitivity, and possibly mediated by stress. This study investigated the relationship between noise sensitivity, perceived stress, and odor sensitivity in a group of men. A quasi-experimental design was used. One-hundred and thirty-four male undergraduate students completed Weinstein's noise sensitivity scale from which a low-sensitivity group (n = 16) and a high-sensitivity (n = 16) group were formed. These two groups were screened for loss in auditory and olfactory detection sensitivity, and completed the perceived stress questionnaire (PSQ) and the chemical sensitivity scale (CSS). One-way analysis of variance and Spearman correlational analyses were performed. Significantly higher scores on the PSQ (P noise-sensitivity group compared to the low noise-sensitivity group. These findings raise the question of whether the relation between noise and odor sensitivity reflects a general environmental sensitivity.

  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. The paradoxical effects of suppressing anxious thoughts during imminent threat.

    Science.gov (United States)

    Koster, Ernst H W; Rassin, Eric; Crombez, Geert; Näring, Gérard W B

    2003-09-01

    In line with the ironic processing theory of Wegner (Psychol. Rev. 101 (1994) 34), it is often argued that the suppression of anxiety-related thoughts results in a paradoxical increase of anxiety and thought intrusions, both after and during the thought suppression. In a sample of undergraduate students (14 men, 18 women), we investigated the effects of suppressing anxious thoughts about an imminent painful electrocutaneous stimulus. During thought suppression, self-reported anxiety and frequency of anxious thoughts did not increase, and duration of anxious thoughts decreased. After thought suppression, participants experienced an increase in self-reported anxiety and the frequency of anxious thoughts. There was no effect upon thought duration. The results support the idea that suppression of anxiety-related thoughts may result in a paradoxical increase in anxiety, and may cause and/or maintain anxiety problems.

  9. Allergic sensitization: screening methods

    DEFF Research Database (Denmark)

    Ladics, Gregory S.; Fry, Jeremy; Goodman, Richard

    2014-01-01

    potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis......Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus...... conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role...

  10. 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...

  11. 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

  12. Ion suppression from blood collection devices

    DEFF Research Database (Denmark)

    Hasselstrøm, Jørgen Bo; Sejr Gothelf, Aase

    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......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...... studied. The blood collection devices were all designed to activate clot formation. They were made of glass with or without silicone coating or plastic containing silicate particles, thrombin or polystyrene particles coated with kaolin. The blood collection devises Venoject and Venosafe were supplied from...

  13. Breaking Magic: Foreign Language Suppresses Superstition.

    Science.gov (United States)

    Hadjichristidis, Constantinos; Geipel, Janet; Surian, Luca

    2017-08-24

    In three studies we found that reading information in a foreign language can suppress common superstitious beliefs. Participants read scenarios either in their native or a foreign language. In each scenario, participants were asked to imagine performing an action (e.g., submitting a job application) under a superstitious circumstance (e.g., broken mirror; four-leaf clover) and to rate how they would feel. Overall, foreign language prompted less negative feelings towards bad-luck scenarios, less positive feelings towards good-luck scenarios, while it exerted no influence on non-superstitious, control scenarios. We attribute these findings to language-dependent memory. Superstitious beliefs are typically acquired and used in contexts involving the native language. As a result, the native language evokes them more forcefully than a foreign language.

  14. 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

  15. Suppression of Drug Resistance in Dengue Virus

    Science.gov (United States)

    Mateo, Roberto; Nagamine, Claude M.

    2015-01-01

    ABSTRACT Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of “dominant drug targets,” in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection. PMID:26670386

  16. Suppression pool in nuclear power plant

    International Nuclear Information System (INIS)

    Hayakumo, Sunao.

    1981-01-01

    Purpose: To improve the efficiency of vapour condensation for the sake of steam-load depression at the time of blowdown, and to prevent the quake of supression pool water at the time of earthquake. Constitution: Double branching plates having a function of a branching vapor stream in two directions when blowing down the vapor and operating the vent safety valve are provided on the central line of the vent tube disposed radially from the center of a reactor housing in a dry well. Further, a vent safety valve exhaust device is provided between the branching plates. When the vapor discharged from the space in the dry well is discharged through the vent tube and the vent safety valve exhaust device into a suppression pool, the stream line is roughly split by the branching plates, and the flows from the adjacent branching plates and the exhaust device collide with one another, thereby improving the condensing action. (Sekiya, K.)

  17. 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

  18. 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…

  19. 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.

  20. 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.

  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. 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

  3. Methods for suppressing isomerization of olefin metathesis products

    Energy Technology Data Exchange (ETDEWEB)

    Firth, Bruce E.; Kirk, Sharon E.; Gavaskar, Vasudeo S.

    2015-09-22

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. The isomerization suppression agent is phosphorous acid, a phosphorous acid ester, phosphinic acid, a phosphinic acid ester or combinations thereof. Methods of refining natural oils are described.

  4. 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.

  5. Old and New Gut Hormone, Gastrin and Acid Suppressive Therapy.

    Science.gov (United States)

    Haruma, Ken; Kamada, Tomoari; Manabe, Noriaki; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Shiotani, Akiko

    2018-03-27

    Gastrin acts physiologically as a gut hormone to stimulate acid secretion after meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin level happens under various conditions including Zollinger-Ellison syndrome, antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As acid suppressive therapy causes hypergastrinemia, the association between acid suppressive therapy and gastric neuroendocrine cell tumor (NET) has been discussed during the past 30 years. In this review article, the definition of hypergastrinemia and the related disorders including acid suppressive therapy and gastric NET are discussed. © 2018 Japanese Gastroenterological Association Published by S. Karger AG, Basel.

  6. 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)-...

  7. 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.

  8. 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.

  9. 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...

  10. Beyond sensitivity analysis

    DEFF Research Database (Denmark)

    Lund, Henrik; Sorknæs, Peter; Mathiesen, Brian Vad

    2018-01-01

    point of view, the typical way of handling this challenge has been to predict future prices as accurately as possible and then conduct a sensitivity analysis. This paper includes a historical analysis of such predictions, leading to the conclusion that they are almost always wrong. Not only...

  11. 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.…

  12. Sense and Sensitivity.

    Science.gov (United States)

    O'Keefe, Barbara J.

    1992-01-01

    Maintains that, although there is little substance to the "political correctness" issue, it has lowered the level of discussion of genuinely important issues. Discusses how communication analysis can contribute to the politically sensitive, but specific and distinct, problems subsumed by the struggle over political correctness…

  13. 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

  14. UNITEC SENS-IT

    Science.gov (United States)

    The UniTec Sens-It is a small gas-sensing device that can measure volatile organic compounds (VOCs). This sensor is used to measure VOCs in applications such as urban air quality, roadside pollution, and (solid waste) landfill monitoring. This operating procedure explains what yo...

  15. Sexuality Sensitive Schooling

    Science.gov (United States)

    McCaughtry, Nate; Dillon, Suzanna; Jones, Elizabeth; Smigell, Sara

    2005-01-01

    American schools, especially their physical education and sport programs, provide some of the most hostile social geographies in all of society for gay youth. With the aim of transforming schools toward more democratic and sexuality sensitive institutions, this paper reviews the literature on sexuality and education. In the review, three themes,…

  16. Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

    Science.gov (United States)

    Noguchi, Y; Saito, A; Miyagi, Y; Yamanaka, S; Marat, D; Doi, C; Yoshikawa, T; Tsuburaya, A; Ito, T; Satoh, S

    2000-06-30

    We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

  17. 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.

  18. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the

  19. Multi-objective optimization of piezoelectric circuitry network for mode delocalization and suppression of bladed disk

    Science.gov (United States)

    Yoo, David; Tang, J.

    2017-04-01

    Since weakly-coupled bladed disks are highly sensitive to the presence of uncertainties, they can easily undergo vibration localization. When vibration localization occurs, vibration modes of bladed disk become dramatically different from those under the perfectly periodic condition, and the dynamic response under engine-order excitation is drastically amplified. In previous studies, it is investigated that amplified vibration response can be suppressed by connecting piezoelectric circuitry into individual blades to induce the damped absorber effect, and localized vibration modes can be alleviated by integrating piezoelectric circuitry network. Delocalization of vibration modes and vibration suppression of bladed disk, however, require different optimal set of circuit parameters. In this research, multi-objective optimization approach is developed to enable finding the best circuit parameters, simultaneously achieving both objectives. In this way, the robustness and reliability in bladed disk can be ensured. Gradient-based optimizations are individually developed for mode delocalization and vibration suppression, which are then integrated into multi-objective optimization framework.

  20. 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.

  1. Contrast-enhanced MR imaging with fat suppression in adult-onset septic spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Longo, M.; Granata, F.; Ricciardi, G.K.; Gaeta, M.; Blandino, A. [Institute of Radiological Sciences, University of Messina, Piazza Immacolata di Marmo, 4, 98121 Messina (Italy)

    2003-03-01

    Spinal infections typically involve vertebrae as well as discs, and for this reason they are called septic spondylodiscitis. Magnetic resonance imaging is the most sensitive imaging method for the evaluation of this group of spinal diseases. The use of contrast-enhanced T1-weighted sequences with fat suppression, if correctly applied, may increase information provided by MRI. Firstly, this technique allows the primary vertebral focus, which often precedes disc involvement, to be identified at a very early stage. When the disease spreads, T1-weighted fat-suppressed gadolinium dimeglumine (Gd-DTPA) enhanced images provide macroscopic details of the primary vertebral focus, disc involvement patterns, and pathways of infection diffusion. All this information, when correlated with laboratory tests, may be useful in identifying the infectious agents (tuberculous vs piogenic forms), thus enabling a suitable therapy to be started. This technique is also useful in the assessment of the real extension of the disease, providing a clear depiction of paravertebral space involvement and of psoas muscle abscesses. Dangerous complications, such as meningitis, myelitis, and epidural abscesses, may be more promptly diagnosed and fully evaluated with fat-suppressed post-contrast T1-weighted images. Finally, this imaging technique may help to differentiate infectious processes from degenerative disorders, extradural neoplastic processes, and rheumatic diseases. (orig.)

  2. Detection and suppression for mechanical resonance in hard disk drives with built-in piezoelectric sensors

    Science.gov (United States)

    Gao, Peng; Lou, Yaolong; Okada, Kanzo

    2002-07-01

    Many components in hard disk drives (HDDs), when in operation, are subjected to vibration due to out of balance of rotating components, inertial impacts under servo driving and dynamic interactions between components. These vibrations have been found to have significant effect upon the servo performance of drive systems. In order to improve the servo performance by reducing the effect of mechanical resonance in HDDs, this paper seeks to detect and suppress mechanical resonance of the head actuator using smart sensors and multi-sensing control techniques. In this regard, sensitive and miniature piezoelectric elements from the polymer-based piezoelectric materials PVDF (polyvinylindin fluoride) or the ceramic-based piezoelectric materials PZT 9lead zircornate titanate) are built in the head actuator for sensing the mechanical vibration. In the experiment, the multi-sensing signals by the piezoelectric sensors and the laser Doppler vibrometer (LDV) are transferred into a voice coil motor (VCM) through a feedback controller so as to actively suppress structural resonance. Numerical simulation and experimental results indicate that the piezoelectric sensors provide an effective way in monitoring the HDD actuator resonance, and the active vibration control strategy is capable of suppressing main mechanical resonance in the head actuator effectively.

  3. 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

  4. Suppression of frequency locking noise in resonator fiber optic gyro by differential detection method

    Science.gov (United States)

    Feng, Lishuang; Zhi, Yinzhou; Lei, Ming; Wang, Junjie

    2014-10-01

    The performance of the resonator fiber optic gyro (RFOG) is influenced by frequency locking noise. This paper proposes a differential detection method (DDM) to suppress the frequency locking noise. First, the frequency locking noise induced by the frequency locking error is described theoretically; the description indicates that it acts as the common-mode noise in the RFOG. In the traditional signal-path detection method (SDM), there is a trade-off between suppressing the frequency locking noise and improving the gyro sensitivity. Thus, a model of the DDM is set up and analyzed. The frequency locking noise can be suppressed using the DDM by adjusting the gains of two lock-in amplifiers. Finally, the experimental setup is established, and the SDM and DDM are compared. When the tested equivalent frequency locking noise is 10.6°/h, the bias stability of the RFOG is improved from 12.9°/h to 1.1°/h by the DDM.

  5. The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation.

    Science.gov (United States)

    Mitsui, Seika; Torii, Kan; Fukui, Hajime; Tsujimura, Kunio; Maeda, Akira; Nose, Mitsuhiko; Nagatsu, Akito; Mizukami, Hajime; Morita, Akimichi

    2010-06-01

    Dendritic cells (DCs) are important for regulating the immune response. We report an herbal medicine compound called falcarindiol that affects DC function. Ethanol extracts of 99 crude drugs that are the main components of 210 traditional Japanese medicines (Kampo medicine) approved by the Ministry of Health, Labor and Welfare in Japan were prepared and screened using the murine epidermal-derived Langerhans cell line XS106. Notopterygii Rhizoma strongly suppressed major histocompatibility complex (MHC) class II expression in XS106 cells. Activity-guided fractionation led to the isolation and identification of falcarindiol as a principal active compound in Notopterygii Rhizoma. Falcarindiol (1-5 microM) dose-dependently suppressed MHC II expression in XS106 cells. Fresh-isolated bone marrow-derived DCs were examined for the production of MHC II, CD80, CD86, interleukin (IL)-12p70, and IL-10. Treatment of bone marrow-derived DCs with 5 muM falcarindiol significantly inhibited lipopolysaccharide-induced phenotype activation and cytokine secretion and inhibited MHC II expression by CD40 ligation, but not phorbol 12-myristate 13-acetate + ionomycin or IL-12. Falcarindiol inhibited DC maturation by blocking the canonical pathway of nuclear factor-kappaB and phosphorylated p38. Topical application of 0.002 and 0.01% falcarindiol before sensitization dose-dependently suppressed delayed-type hypersensitivity to ovalbumin (p Falcarindiol induces immunosuppressive effects in vitro and in vivo and might be a novel therapy for autoimmune or allergic diseases.

  6. [Construction of suppression subtracted cDNA library of deltamethrin-resistant Aedes albopictus].

    Science.gov (United States)

    Wu, Jia-hong; Zhao, Tong-yan; Dong, Yan-de

    2006-08-01

    To construct the suppression subtracted cDNA library of deltamethrin-resistant Aedes albopictus. Total RNA was extracted from the deltamethrin-resistant (R-lab) and -sensitive (S-lab) isolates, mRNA was obtained after purification. Double stranded cDNAs were synthesized after reverse transcription. Two subtractions were performed by suppression subtractive hybridization with S-lab as tester and R-lab as driver or S-lab as driver and R-lab as tester. Enriched different expressed cDNA was cloned into pMD18-T vector to construct subtractive libraries. The subtracted cDNA libraries contained 580 and 477 positive clones respectively. The PCR results of 150 clones picked randomly from each library showed that the positive ratio of constructed cDNA libraries was 93%, with a length of cDNA fragments ranged from 150bp to 750bp. The suppression subtracted cDNA library of deltamethrin-resistant Ae. albopictus is constructed.

  7. Deciphering the RhizosphereMicrobiome for Disease-Suppressive Bacteria

    NARCIS (Netherlands)

    Mendes, R.; Kruijt, M.; Bruijn, de I.; Dekkers, E.; Voort, van der M.; Schneider, J.H.M.; Piceno, Y.M.; DeSantis, T.Z.; Andersen, G.L.; Bakker, P.A.H.M.; Raaijmakers, J.M.

    2011-01-01

    Disease-suppressive soils are exceptional ecosystems in which crop plants suffer less from specific soil-borne pathogens than expected owing to the activities of other soil microorganisms. For most disease-suppressive soils, the microbes and mechanisms involved in pathogen control are unknown. By

  8. 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 ...

  9. One-tone suppression in the frog auditory nerve

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    frequencies ranged from 700 to 1200 Hz. Spontaneous activities for the fibers showing one-tone suppression ranged from 3 to 75 spikes/s. Spontaneous activities above 40 spikes/s and the phenomenon of one-tone suppression itself has not been reported previously for frogs. The population of fibers showing one...

  10. Emotion suppression reduces hippocampal activity during successful memory encoding.

    Science.gov (United States)

    Binder, Julia; de Quervain, Dominique J-F; Friese, Malte; Luechinger, Roger; Boesiger, Peter; Rasch, Björn

    2012-10-15

    People suppressing their emotions while facing an emotional event typically remember it less well. However, the neural mechanisms underlying the impairing effect of emotion suppression on successful memory encoding are not well understood. Because successful memory encoding relies on the hippocampus and the amygdala, we hypothesized that memory impairments due to emotion suppression are associated with down-regulated activity in these brain areas. 59 healthy females were instructed either to simply watch the pictures or to down-regulate their emotions by using a response-focused emotion suppression strategy. Brain activity was recorded using functional magnetic resonance imaging (fMRI), and free recall of pictures was tested afterwards. As expected, suppressing one's emotions resulted in impaired recall of the pictures. On the neural level, the memory impairments were associated with reduced activity in the right hippocampus during successful encoding. No significant effects were observed in the amygdala. In addition, functional connectivity between the hippocampus and the right dorsolateral prefrontal cortex was strongly reduced during emotion suppression, and these reductions predicted free-recall performance. Our results indicate that emotion suppression interferes with memory encoding on the hippocampal level, possibly by decoupling hippocampal and prefrontal encoding processes, suggesting that response-focused emotion suppression might be an adaptive strategy for impairing hippocampal memory formation in highly arousing situations. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Hearing aid noise suppression and working memory function

    DEFF Research Database (Denmark)

    Fischer, Rosa-Linde; Neher, Tobias; Wagener, Kirsten C.

    Research findings concerning the relation between outcome from hearing aid (HA) noise suppression and working memory function are unclear. The current study thus investigated the effects of three noise suppression algorithms on auditory working memory as well as the relation with reading span...

  12. Hearing aid noise suppression and working memory function

    DEFF Research Database (Denmark)

    Neher, Tobias; Wagener, Kirsten C.; Fischer, Rosa-Linde

    2018-01-01

    OBJECTIVE: Research findings concerning the relation between benefit from hearing aid (HA) noise suppression and working memory function are inconsistent. The current study thus investigated the effects of three noise suppression algorithms on auditory working memory and the relation with reading...

  13. Position Sensitive Gaseous Photomultipliers

    CERN Document Server

    Martinengo, P; Peskov, V

    2010-01-01

    Advances in the technologies associated with position sensitive gaseous detectors especially featuring CsI as reflective photoconverters will be reviewed. These photodetectors represent the most effective solution for what concerns cost and performance in the case of large area Cherenkov imaging applications in relatively low rate (or low occupancy) high energy physics and astrophysics experiments. Moreover, they are the only choice when the Cherenkov detector is embedded in a magnetic field. Recently proposed single photon MPGDs (Micropattern Gaseous Detectors) will be also discussed in view of the successful efforts so far made to extend their sensitivity to visible light. With some modifications, photosensitive gaseous detectors can also be used in the imaging of X-rays and particles.

  14. Integrated Sensitivity Analysis Workflow

    Energy Technology Data Exchange (ETDEWEB)

    Friedman-Hill, Ernest J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoffman, Edward L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gibson, Marcus J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Clay, Robert L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-08-01

    Sensitivity analysis is a crucial element of rigorous engineering analysis, but performing such an analysis on a complex model is difficult and time consuming. The mission of the DART Workbench team at Sandia National Laboratories is to lower the barriers to adoption of advanced analysis tools through software integration. The integrated environment guides the engineer in the use of these integrated tools and greatly reduces the cycle time for engineering analysis.

  15. Naegleria fowleri: trimethoprim sensitivity.

    Science.gov (United States)

    Cerva, L

    1980-09-26

    Trimethoprim in a concentration of 4 micrograms per milliter of Bacto-Casitone (Difco) medium inhibits the growth of nonvirulent Naegleria fowleri isolates. The growth of virulent strains is unaffected even with 400 micrograms of the drug per milliliter of medium. Differences in sensitivity constitute the possibility of a simple selection of environmental isolates. The pathogenicity and virulence of Naegleria species may be connected with the metabolism of folic acid.

  16. 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.

  17. Oxygen sensitive microwells.

    Science.gov (United States)

    Sinkala, Elly; Eddington, David T

    2010-12-07

    Oxygen tension is critical in a number of cell pathways but is often overlooked in cell culture. One reason for this is the difficulty in modulating and assessing oxygen tensions without disturbing the culture conditions. Toward this end, a simple method to generate oxygen-sensitive microwells was developed through embossing polystyrene (PS) and platinum(ii) octaethylporphyrin ketone (PtOEPK) thin films. In addition to monitoring the oxygen tension, microwells were employed in order to isolate uniform clusters of cells in microwells. The depth and width of the microwells can be adapted to different experimental parameters easily by altering the thin film processing or embossing stamp geometries. The thin oxygen sensitive microwell substrate is also compatible with high magnification modalities such as confocal imaging. The incorporation of the oxygen sensor into the microwells produces measurements of the oxygen tension near the cell surface. The oxygen sensitive microwells were calibrated and used to monitor oxygen tensions of Madin-Darby Canine Kidney Cells (MDCKs) cultured at high and low densities as a proof of concept. Wells 500 µm in diameter seeded with an average of 330 cells exhibited an oxygen level of 12.6% whereas wells seeded with an average of 20 cells per well exhibited an oxygen level of 19.5%, a 35.7% difference. This platform represents a new tool for culturing cells in microwells in a format amenable to high magnification imaging while monitoring the oxygen state of the culture media.

  18. 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.)

  19. Reproductive suppression follows threats to child survival.

    Science.gov (United States)

    Saxton, K B; Gemmill, A; Catalano, R A

    2017-05-01

    Natural selection presumably conserved mechanisms that allow females to block or terminate gestation when environmental circumstances threaten the survival of offspring. One example of this adaptive reproductive suppression, the Bruce effect, has been identified in several species, both in the laboratory and in the wild. Although descriptive epidemiology reports low fertility among women experiencing stressful circumstances, attempts to detect a Bruce effect in humans have been rare and limited. We contribute to this limited work by examining the relationship between the odds of child death and the sex ratio at birth in Sweden for the years 1751-1840. We find evidence of a generalized Bruce effect in humans in that unexpected changes in child mortality predict opposite unexpected changes in the secondary sex ratio in the following year, even after adjusting for period life expectancy. Our analysis broadens the scope of the Bruce effect literature to include humans, suggesting that women, through noncognitive decisional biology, adjust reproductive strategies and investments in response to changing environmental conditions. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  20. 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.

  1. 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)

  2. Suppression of intrinsic roughness in encapsulated graphene

    Science.gov (United States)

    Thomsen, Joachim Dahl; Gunst, Tue; Gregersen, Søren Schou; Gammelgaard, Lene; Jessen, Bjarke Sørensen; Mackenzie, David M. A.; Watanabe, Kenji; Taniguchi, Takashi; Bøggild, Peter; Booth, Timothy J.

    2017-07-01

    Roughness in graphene is known to contribute to scattering effects which lower carrier mobility. Encapsulating graphene in hexagonal boron nitride (hBN) leads to a significant reduction in roughness and has become the de facto standard method for producing high-quality graphene devices. We have fabricated graphene samples encapsulated by hBN that are suspended over apertures in a substrate and used noncontact electron diffraction measurements in a transmission electron microscope to measure the roughness of encapsulated graphene inside such structures. We furthermore compare the roughness of these samples to suspended bare graphene and suspended graphene on hBN. The suspended heterostructures display a root mean square (rms) roughness down to 12 pm, considerably less than that previously reported for both suspended graphene and graphene on any substrate and identical within experimental error to the rms vibrational amplitudes of carbon atoms in bulk graphite. Our first-principles calculations of the phonon bands in graphene/hBN heterostructures show that the flexural acoustic phonon mode is localized predominantly in the hBN layer. Consequently, the flexural displacement of the atoms in the graphene layer is strongly suppressed when it is supported by hBN, and this effect increases when graphene is fully encapsulated.

  3. 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.

  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. Control of stochastic sensitivity in a stabilization problem for gas discharge system

    Energy Technology Data Exchange (ETDEWEB)

    Bashkirtseva, Irina [Ural Federal University, Lenina, 51, Ekaterinburg, 620000 (Russian Federation)

    2015-11-30

    We consider a nonlinear dynamic stochastic system with control. A problem of stochastic sensitivity synthesis of the equilibrium is studied. A mathematical technique of the solution of this problem is discussed. This technique is applied to the problem of the stabilization of the operating mode for the stochastic gas discharge system. We construct a feedback regulator that reduces the stochastic sensitivity of the equilibrium, suppresses large-amplitude oscillations, and provides a proper operation of this engineering device.

  6. Conditioned suppression to odorous stimuli in pigeons, 12

    Science.gov (United States)

    Henton, Wendon W.

    1969-01-01

    The conditioned suppression technique was employed to establish criterion discrimination of an amyl acetate concentration of 3% of vapor saturation, and to generate differential response rates in the presence of equal concentrations of amyl acetate and butyl acetate. The magnitude of suppression was also recorded as a function of amyl acetate concentration, with the concentrations presented in descending, ascending, and irregular series. The three stimulus presentation procedures generated approximately equivalent suppression versus concentration functions. Amyl acetate suppression thresholds were 0.16%, 0.50%, and 0.73% of vapor saturation for three subjects. Amyl acetate, butyl acetate, and butyric acid thresholds for two additional subjects were approximately 0.10% of vapor saturation. No suppression was recorded during control trials. PMID:5778311

  7. 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

  8. 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)

  9. 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.)

  10. 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

  11. 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

  12. Perceptual Sensitivity and Response to Strong Stimuli Are Related.

    Science.gov (United States)

    Bolders, Anna C; Tops, Mattie; Band, Guido P H; Stallen, Pieter Jan M

    2017-01-01

    To shed new light on the long-standing debate about the (in)dependence 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.

  13. 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.

  14. 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.

  15. 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.

  16. Indirect blue light does not suppress nocturnal salivary melatonin in humans in an automobile setting.

    Science.gov (United States)

    Lerchl, Alexander; Schindler, Carina; Eichhorn, Karsten; Kley, Franziska; Erren, Thomas C

    2009-09-01

    In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as being probably carcinogenic to humans (Group 2A). In this context, light exposure during the night plays a key role because it can suppress nocturnal melatonin levels when exposures exceed a certain threshold. Blue light around 464 nm is most effective in suppressing melatonin because of the spectral sensitivity of melanopsin, a recently discovered photopigment in retinal ganglion cells; the axons of these cells project to the suprachiasmatic nucleus, a circadian master clock in the brain. Due to advances in light technologies, normal tungsten light bulbs are being replaced by light-emitting diodes which produce quasi-monochromatic or white light. The objective of this study was to assess whether the light-melanopsin-melatonin axis might be affected in automobiles at night which employ the new generation diodes. To this end, we have tested in an experimental automobile setting whether indirect blue light (lambda(max) = 465 nm) at an intensity of 0.22 or 1.25 lx can suppress salivary melatonin levels in 12 male volunteers (age range 17-27 years) who served as their own controls. Daytime levels were low (2.7 +/- 0.5 pg/mL), and night-time levels without light exposure were high (14.5 +/- 1.1 pg/mL), as expected. Low-intensity light exposures had no significant effect on melatonin levels (0.22 lx: 17.2 +/- 2.8 pg/mL; P > 0.05; 1.25 lx: 12.6 +/- 2.0 pg/mL; P > 0.05). It is concluded that indirect blue light exposures in automobiles up to 1.25 lx do not cause unintentional chronodisruption via melatonin suppression.

  17. 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, p<0.001), 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.

  18. [Fat-suppressing STIR sequences with and without contrast media in the MRT of ENT tumors].

    Science.gov (United States)

    Brüning, R; Heuck, A; Naegele, M; Seelos, K; Vahlensieck, M; Reiser, M

    1994-05-01

    Fat-suppressed STIR (short TI inversion recovery) sequences were compared to plain and contrast-enhanced T1-weighted SE sequences of head and neck tumors. 19 patients underwent MR imaging on a 0.5 Telsa system (T5-II, Philips). STIR imaging parameters: TR/TE = 1000/20 ms, inversion pulse 100 ms. All films were read by four radiologists. The image quality was graded: score from 0 to 5, by means that grade 5 = optimal quality. Sensitivity was 89% in STIR, 96% in SE sequences. Tumor delineation was graded good in the enhanced T1-weighted and enhanced fat suppression images. The unenhanced imaging was superior in STIR (STIR/T1 = 2.8/2.43). The tumor contrast was best in contrast enhanced and plain STIR sequences (STIR contrast = 3.41), and in the contrast enhanced T1-weighted SE (3.33). STIR almost equaled T1 post-contrast in respect of tumour conspicuity, but the sensitivity was lower. STIR can be a supplement to SE, but cannot substitute T1 postcontrast. The combined use is expected to have the highest assessment value.

  19. Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma.

    Science.gov (United States)

    Kittipongdaja, Wasakorn; Wu, Xuesong; Garner, Justine; Liu, Xiping; Komas, Steven M; Hwang, Sam T; Schieke, Stefan M

    2015-09-01

    The mTOR pathway is a master regulator of cellular growth and metabolism. The biosynthetic and energetic demand of rapidly proliferating cells such as cancer cells is met by metabolic adaptations such as an increased glycolytic rate known as the Warburg effect. Herein, we characterize the anti-tumor effect of rapamycin in a mouse model of T-cell lymphoma and examine the metabolic effects in vitro. The murine T-cell lymphoma line, MBL2, and human cutaneous T-cell lymphoma (CTCL) lines, HH and Hut78, were used in syngeneic or standard NSG mouse models to demonstrate a marked suppression of tumor growth by rapamycin accompanied by inhibition of mTORC1/2. Analysis of the metabolic phenotype showed a substantial reduction in the glycolytic rate and glucose utilization in rapamycin-treated lymphoma cells. This was associated with reduced expression of glucose transporters and glycolytic enzymes in cultured cells and xenograft tumors. As a result of the decrease in glycolytic state, rapamycin-treated cells displayed reduced sensitivity to low-glucose conditions but continued to rely on mitochondrial oxidative phosphorylation (OXPHOS) with sensitivity to inhibition of OXPHOS. Taken together, we demonstrate that rapamycin suppresses growth of T-cell lymphoma tumors and leads to a reduction in aerobic glycolysis counteracting the Warburg effect of cancer cells.

  20. APCCdc20 Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction

    Science.gov (United States)

    Wan, Lixin; Tan, Mingjia; Yang, Jie; Inuzuka, Hiroyuki; Dai, Xiangpeng; Wu, Tao; Liu, Jia; Shaik, Shavali; Chen, Guoan; Deng, Jing; Malumbres, Marcos; Letai, Anthony; Kirschner, Marc W.; Sun, Yi; Wei, Wenyi

    2014-01-01

    SUMMARY APCCdc20 plays pivotal roles in governing mitotic progression. By suppressing APCCdc20, anti-mitotic agents activate the spindle-assembly-checkpoint (SAC), and induce apoptosis after prolonged-treatment, while depletion of endogenous Cdc20 suppresses in vivo tumorigenesis in part by triggering mitotic arrest and subsequent apoptosis. However, the molecular mechanism(s) underlying apoptosis induced by Cdc20 abrogation remains poorly understood. Here we report that the BH3-only pro-apoptotic protein Bim is an APCCdc20 target, as such depletion of Cdc20 sensitizes cells to apoptotic stimuli. Strikingly, Cdc20 and multiple APC-core components were identified in an siRNA screen that upon knockdown sensitizes otherwise resistant cancer cells to chemo-radiation therapies in a Bim-dependent manner. Consistently, human Adult-T-cell-Leukemia (ATL) cells that acquire elevated APCCdc20 activity via expressing the Tax-viral-oncoprotein, exhibit reduced Bim levels and resistance to anti-cancer agents. These results reveal an important role for APCCdc20 in governing apoptosis, strengthening the rationale for developing specific Cdc20 inhibitors as effective anti-cancer agents. PMID:24871945

  1. 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

  2. Genetic Control of Mosquitoes: population suppression strategies

    Directory of Open Access Journals (Sweden)

    André Barretto Bruno Wilke

    2012-10-01

    Full Text Available Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

  3. 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...... controls at baseline, immediately after and four hours after a controlled chemical (n-butanol) exposure, in an exposure chamber previously verified to induce symptom elicitation in MCS subjects. In manuscript III, mucosal lining fluid samples were collected and levels of 19 cytokines and chemokines were...

  4. SENSITIVE PRESSURE GAUGE

    Science.gov (United States)

    Ball, W.P.

    1961-01-01

    An electron multiplier device is described. It has a plurality of dynodes between an anode and cathode arranged to measure pressure, temperature, or other environmental physical conditions that proportionately iinfuences the quantity of gas molecules between the dynodes. The output current of the device is influenced by the reduction in electron multiplication at the dynodes due to energy reducing collisions of the electrons with the gas molecules between the dynodes. More particularly, the current is inversely proportional to the quantity of gas molecules, viz., the gas pressure. The device is, hence, extremely sensitive to low pressures.

  5. When thought suppression backfires: its moderator effect on eating psychopathology.

    Science.gov (United States)

    Ferreira, Cláudia; Palmeira, Lara; Trindade, Inês A; Catarino, Francisca

    2015-09-01

    Recently, several studies have pointed the importance of thought suppression as a form of experiential avoidance in different psychopathological conditions. Thought suppression may be conceptualized as an attempt to decrease or eliminate unwanted internal experiences. However, it encloses a paradoxical nature, making those thoughts hyper accessible and placing an extra burden on individuals. This avoidance process has been associated with several psychopathological conditions. However, its role in eating psychopathology remains unclear. The present study aims to explore the moderation effect of thought suppression on the associations between body image-related unwanted internal experiences (unfavorable social comparison through physical appearance and body image dissatisfaction) and eating psychopathology severity in a sample of 211 female students. Correlational analyses showed that thought suppression is associated with psychological inflexibility and eating disorders' main risk factors and symptoms. Moreover, two independent analyses revealed that thought suppression moderates, as it amplifies, the impact of unfavorable social comparisons through physical appearance (model 1) and body image dissatisfaction (model 2) on disordered eating attitudes and behaviors. Hence, for the same level of these body-related internal experiences, young females who reveal higher levels of thought suppression present higher eating psychopathology. Taken together, these findings highlight the key role of thought suppression in eating psychopathology and present important clinical implications.

  6. The use of repetition suppression paradigms in developmental cognitive neuroscience.

    Science.gov (United States)

    Nordt, Marisa; Hoehl, Stefanie; Weigelt, Sarah

    2016-07-01

    Repetition suppression paradigms allow a more detailed look at brain functioning than classical paradigms and have been applied vigorously in adult cognitive neuroscience. These paradigms are well suited for studies in the field of developmental cognitive neuroscience as they can be applied without collecting a behavioral response and across all age groups. Furthermore, repetition suppression paradigms can be employed in various neuroscience techniques, such as functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG) and magnetoencephalography (MEG). In the present article we review studies using repetition suppression paradigms in developmental cognitive neuroscience covering the age range from infancy to adolescence. Our first goal is to point out characteristics of developmental repetition suppression effects. In doing so, we discuss the relationship of the direction of repetition effects (suppression vs enhancement) with developmental factors, and address the question how the direction of repetition effects might be related to looking-time effects in behavioral infant paradigms, the most prominently used behavioral measure in infant research. To highlight the potential of repetition suppression paradigms, our second goal is to provide an overview on the insights recently obtained by applying repetition paradigms in neurodevelopmental studies, including research on children with autism spectrum disorders (ASDs). We conclude that repetition suppression paradigms are valuable tools for investigating neurodevelopmental processes, while at the same time we highlight the necessity for further studies that disentangle methodological and developmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients.

    Science.gov (United States)

    Collins, Sean E; Grant, Philip M; Shafer, Robert W

    2016-01-01

    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.

  8. Suppressing voltage transients in high voltage power supplies

    International Nuclear Information System (INIS)

    Lickel, K.F.; Stonebank, R.

    1979-01-01

    A high voltage power supply for an X-ray tubes includes voltage adjusting means, a high voltage transformer, switch means connected to make and interrupt the primary current of the transformer, and over-voltage suppression means to suppress the voltage transient produced when the current is switched on. In order to reduce the power losses in the suppression means, an impedance is connected in the transformer primary circuit on operation of the switch means and is subsequently short-circuited by a switch controlled by a timer after a period which is automatically adjusted to the duration of the transient overvoltage. (U.K.)

  9. 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 measured here for seven subjects, both for short- and long-latency CEOAEs. Long-latency CEOAEs (duration >20ms) typically indicate the presence of synchronised spontaneous otoacoustic emissions (SSOAEs). Temporal suppression can only be linked to changes in CEOAE-compression if the suppressor-click affects...

  10. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

    Science.gov (United States)

    Pagani, Olivia; Regan, Meredith M; Walley, Barbara A; Fleming, Gini F; Colleoni, Marco; Láng, István; Gomez, Henry L; Tondini, Carlo; Burstein, Harold J; Perez, Edith A; Ciruelos, Eva; Stearns, Vered; Bonnefoi, Hervé R; Martino, Silvana; Geyer, Charles E; Pinotti, Graziella; Puglisi, Fabio; Crivellari, Diana; Ruhstaller, Thomas; Winer, Eric P; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N; Bernhard, Jürg; Luo, Weixiu; Ribi, Karin; Viale, Giuseppe; Coates, Alan S; Gelber, Richard D; Goldhirsch, Aron; Francis, Prudence A

    2014-07-10

    Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

  11. Oxytocin decreases sweet taste sensitivity in mice.

    Science.gov (United States)

    Sinclair, Michael S; Perea-Martinez, Isabel; Abouyared, Marianne; St John, Steven J; Chaudhari, Nirupa

    2015-03-15

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Suppression of the dayside magnetopause surface modes

    Directory of Open Access Journals (Sweden)

    Pilipenko V.A.

    2017-12-01

    Full Text Available Magnetopause surface eigenmodes were suggested as a potential source of dayside high-latitude broadband pulsations in the Pc5-6 band (frequency about 1–2 mHz. However, the search for a ground signature of these modes has not provided encouraging results. The comparison of multi-instrument data from Svalbard with the latitudinal structure of Pc5-6 pulsations, recorded by magnetometers covering near-cusp latitudes, has shown that often the latitudinal maximum of pulsation power occurs about 2–3° deeper in the magnetosphere than the dayside open-closed field line boundary (OCB. The OCB proxy was determined from SuperDARN radar data as the equatorward boundary of enhanced width of a return radio signal. The OCB-ULF correspondence is further examined by comparing the latitudinal profile of the near-noon pulsation power with the equatorward edge of the auroral red emission from the meridian scanning photometer. In most analyzed events, the “epicenter” of Pc5-6 power is at 1–2° lower latitude than the optical OCB proxy. Therefore, the dayside Pc5-6 pulsations cannot be associated with the ground image of the magnetopause surface modes or with oscillations of the last field line. A lack of ground response to these modes beneath the ionospheric projection of OCB seems puzzling. As a possible explanation, we suggest that a high variability of the outer magnetosphere near the magnetopause region may suppress the excitation efficiency. To quantify this hypothesis, we consider a driven field line resonator terminated by conjugate ionospheres with stochastic fluctuations of its eigenfrequency. A solution of this problem predicts a substantial deterioration of resonant properties of MHD resonator even under a relatively low level of background fluctuations. This effect may explain why there is no ground response to magnetopause surface modes or oscillations of the last field line at the OCB latitude, but it can be seen at somewhat lower latitudes

  13. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

    Science.gov (United States)

    Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

    2012-03-01

    The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Context Sensitive Health Informatics

    DEFF Research Database (Denmark)

    Healthcare information technologies are now routinely deployed in a variety of healthcare contexts. These contexts differ widely, but the smooth integration of IT systems is crucial, so the design, implementation, and evaluation of safe, effective, efficient and easy to adopt health informatics...... involves careful consideration of both human and organizational factors. This book presents the proceedings of the Context Sensitive Health Informatics (CSHI) conference, held in Copenhagen, Denmark, in August 2013. The theme of this year’s conference is human and sociotechnical approaches. The Human......: patients and IT; usability test and evaluation; work tasks and related contexts; human factors and simulation; and context and systems design, and outline theories and models for studying contextual issues and insights related to how health information technologies can be better designed to accommodate...

  15. Disgust sensitivity and anorexia nervosa

    DEFF Research Database (Denmark)

    Nielsen, Ruth Aharoni; Hertz, Marianne M

    2012-01-01

    Previous studies found inconsistent differences in disgust sensitivity between patients with a variety of eating disorders and normal controls.......Previous studies found inconsistent differences in disgust sensitivity between patients with a variety of eating disorders and normal controls....

  16. MOVES regional level sensitivity analysis

    Science.gov (United States)

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  17. Culture-sensitive psychotraumatology

    Directory of Open Access Journals (Sweden)

    Ulrich Schnyder

    2016-07-01

    Full Text Available Background: Although there is some evidence of the posttraumatic stress disorder (PTSD construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods: The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results: As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions: In summary

  18. [Effect of moderate alcohol consumption on insulin sensitivity].

    Science.gov (United States)

    Abel, Tatjána; Fehér, János

    2009-12-06

    Moderate alcohol consumption has been reported to be associated with lower risk for both cardiovascular disease and type 2 diabetes. An explanation for these epidemiologic observations is not entirely clear. Alcohol raises high-density lipoprotein (HDL) cholesterol levels. Other potential beneficial mechanisms have been proposed including anti-inflammatory and anti-thrombotic effects. The association between moderate alcohol consumption and insulin sensitivity is still under debate. Possible mechanisms include elevation of adiponectin level, reduction of C-reactive protein and suppression of free fatty acid release from adipose tissue.

  19. Electrocardiographic Responses During Fire Suppression and Recovery Among Experienced Firefighters.

    Science.gov (United States)

    Al-Zaiti, Salah; Rittenberger, Jon C; Reis, Steven E; Hostler, David

    2015-09-01

    We sought to evaluate the impact of high-intensity exertion and heat stress on electrocardiographic changes during fire suppression and recovery. Healthy firefighters completed a live-fire training evolution. Each firefighter was randomly assigned to complete either two or three intervals of fire suppression tasks followed by a structured recovery. Firefighters were continuously monitored using 12-lead Holter electrocardiogram. Most firefighters (71.4%) exceeded their maximum heart rate and one third had pathological ST events. Nearly one third of each of these abnormalities persisted throughout recovery period. Longer fire suppression intervals did not affect the incidence of these abnormalities. Fire suppression is associated with ST-segment changes among firefighters at low risk for cardiovascular disease. These abnormalities continued into initial recovery even though cooling and rehydration were provided.

  20. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  1. Proximity Glare Suppression for Astronomical Coronagraphy, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — There is a critical need for stray light suppression in advanced astronomical telescopes and imaging systems. For optical instruments that are required to view...

  2. Population Suppression of Subterranean Termites by Slow-Acting Toxicants

    Science.gov (United States)

    Nan-Yao Su; Rudolf H. Scheffrahn

    1991-01-01

    Historic background and the concept of slow-acting toxicants for population suppression of subterranean termites are reviewed. Information needed for development of bait-toxicants and studies needed to generate such information are summarized.

  3. Theory of suppression of loss cone instabilities by electron beams

    International Nuclear Information System (INIS)

    Sinha, A.; Sinha, M.

    1981-01-01

    A new mechanism for the suppression of Drift Cyclotron Loss Cone instabilities by electron beams injected along the field lines is given. The mechanism explains some of the recent observations. (author)

  4. Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-β.

    Science.gov (United States)

    Ohishi, Jun; Aoki, Mikiko; Nabeshima, Kazuki; Suzumiya, Junji; Takeuchi, Tamotsu; Ogose, Akira; Hakozaki, Michiyuki; Yamashita, Yuichi; Iwasaki, Hiroshi

    2013-05-04

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 - 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.

  5. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

    Science.gov (United States)

    Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel

    2014-02-01

    Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

  6. Epicutaneous immunization with protein antigen TNP-Ig and NOD2 ligand muramyl dipeptide (MDP) reverses skin-induced suppression of contact hypersensitivity.

    Science.gov (United States)

    Majewska-Szczepanik, Monika; Dorożyńska, Iwona; Strzępa, Anna; Szczepanik, Marian

    2014-02-01

    Epicutaneous (EC) immunization offers a new method of a needle-free and self-administrable immunization by using a topically applied patch to deliver vaccine. We have previously shown that EC immunization with hapten-conjugated protein antigen TNP-Ig prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. Our further work showed that EC immunization with TNP-Ig and Toll-like receptor (TLR) ligands prior to hapten sensitization reverses skin-induced suppression. Animal model of contact hypersensitivity was used to study reversal of skin-induced suppression. Current work showed that EC immunization with protein antigen TNP-Ig and MDP NOD2 agonist - muramyldipeptide (L isoform) reverses skin-induced suppression of CHS. On the other hand L18-MDP NOD2 agonist - muramyldipeptide with a C18 fatty acid chain and MDP control - negative control for MDP - muramyldipeptide (D isoform, inactive) did not reverse skin-induced suppression. "Transfer in" experiment showed that reversal of skin-induced suppression can be adoptively transferred with lymphoid cells isolated from donors EC treated with TNP-Ig and MDP NOD2 agonist. Moreover, experiment employing two non-cross-reacting antigens TNP-Ig and OX-Ig proved that reversal of skin-induced suppression is antigen specific. Additionally, lymph node cells isolated from mice EC immunized with TNP-Ig and MDP NOD2 agonist produced increased level of IFN-γ suggesting that this cytokine might be involved in reversal of skin-induced suppression. This work shows that EC immunization with protein antigen plus NOD2 ligand MDP may be a potential tool to increase the immunogenicity of weekly immunogenic antigens. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories.

    Science.gov (United States)

    Noreen, Saima; O'Connor, Akira R; MacLeod, Malcolm D

    2016-01-01

    Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one's attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC) and the mid-ventrolateral prefrontal cortex (VLPFC) regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think) or to suppress (no-think) the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution). Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex, there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

  8. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories

    Directory of Open Access Journals (Sweden)

    Saima eNoreen

    2016-03-01

    Full Text Available Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one's attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC and the mid-ventrolateral prefrontal cortex (VLPFC regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think or to suppress (no-think the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution. Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

  9. Surround Suppression Maps in the Cat Primary Visual Cortex

    Directory of Open Access Journals (Sweden)

    Matthieu P Vanni

    2013-04-01

    Full Text Available In the primary visual cortex and higher-order areas, it is well known that the stimulation of areas surrounding the classical receptive field of a neuron can inhibit its responses. In the primate area MT, this surround suppression was shown to be spatially organized into high and low suppression modules. However, such an organization hasn’t been demonstrated yet in the primary visual cortex. Here, we used optical imaging of intrinsic signals to spatially evaluate surround suppression in the cat visual cortex. The magnitude of the response was measured in areas 17 and 18 for stimuli with different diameters, presented at different eccentricities. Delimited regions of the cortex were revealed by circumscribed stimulations of the visual field (cortical response field. Increasing the stimulus diameter increased the spread of cortical activation. In the cortical response field, the optimal stimulation diameter and the level of suppression were evaluated. Most pixels (3/4 exhibited surround suppression profiles. The optimal diameter, corresponding to a population of receptive fields, was smaller in area 17 (22 deg. than in area 18 (36 deg. in accordance with electrophysiological data. No difference in the suppression strength was observed between both areas (A17: 25%, A18: 21%. Further analysis of our data revealed the presence of surround modulation maps, organized in low and high suppression domains. We also developed a statistical method to confirm the existence of this cortical map and its neuronal origin. The organization for center/surround suppression observed here at the level of the primary visual cortex is similar to those found in higher order areas in primates (e.g. area MT and could represent a strategy to optimize figure ground discrimination.

  10. Surround suppression maps in the cat primary visual cortex

    OpenAIRE

    Vanni, Matthieu P.; Casanova, Christian

    2013-01-01

    In the primary visual cortex and higher-order areas, it is well known that the stimulation of areas surrounding the classical receptive field of a neuron can inhibit its responses. In the primate area middle temporal (MT), this surround suppression was shown to be spatially organized into high and low suppression modules. However, such an organization has not been demonstrated yet in the primary visual cortex. Here, we used optical imaging of intrinsic signals to spatially evaluate surround s...

  11. Voluntary driven elbow orthosis with speed controlled tremor suppression

    Directory of Open Access Journals (Sweden)

    Gil eHerrnstadt

    2016-03-01

    Full Text Available Robotic technology is gradually becoming commonplace in the medical sector and in the service of patients. Medical conditions that have benefited from significant technological development include stroke, for which rehabilitation with robotic devices is administered, and surgery assisted by robots. Robotic devices have also been proposed for assistance of movement disorders. Pathological tremor, among the most common movement disorders, is such one example. In practice, the dissemination and availability of tremor suppression robotic systems has been limited. Devices in the marketplace tend to either be non-ambulatory or to target specific functions such as eating and drinking.We have developed a one degree-of-freedom (DOF elbow orthosis that could be worn by an individual with tremor. A speed controlled voluntary driven suppression approach is implemented with the orthosis. Typically tremor suppression methods estimate the tremor component of the signal and produce a canceling counterpart signal. The suggested approach, instead estimates the voluntary component of the motion. A controller then actuates the orthosis based on the voluntary signal while simultaneously rejecting the tremorous motion.In this work, we tested the suppressive orthosis using a 1 DOF robotic system that simulates the human arm. The suggested suppression approach does not require a model of the human arm. Moreover, the human input along with the orthosis forearm gravitational forces, of nonlinear nature, are considered as part of the disturbance to the suppression system. Therefore, the suppression system can be modeled linearly. Nevertheless, the orthosis forearm gravitational forces can be compensated by the suppression system.The electromechanical design of the orthosis is presented, and data from an Essential Tremor patient is used as the human input. Velocity tracking results demonstrate an RMS error of 0.31 rad/s, and a power spectral density shows a reduction of

  12. Methods for suppressing isomerization of olefin metathesis products

    Energy Technology Data Exchange (ETDEWEB)

    Firth, Bruce E.; Kirk, Sharon E.

    2015-10-27

    A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent that includes nitric acid to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. Methods of refining a natural oil are described.

  13. Interferometric crosstalk suppression using polarization multiplexing technique and an SOA

    DEFF Research Database (Denmark)

    Liu, Fenghai; Xueyan, Zheng; Pedersen, Rune Johan Skullerud

    2000-01-01

    Interferometric crosstalk can be greatly suppressed at 10Gb/s and 20Gb/s by using a gain saturated SOA and a polarization multiplexing technique that eliminates impairments like waveform and extinction ratio degradation from the SOA.......Interferometric crosstalk can be greatly suppressed at 10Gb/s and 20Gb/s by using a gain saturated SOA and a polarization multiplexing technique that eliminates impairments like waveform and extinction ratio degradation from the SOA....

  14. Application of phase coherent transform to cloud clutter suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ng, L.C. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    This paper describes a tracking algorithm using frame-to-frame correlation with frequency domain clutter suppression. Clutter suppression was mechanized via a `Phase Coherent Transform` (PCT) approach. This approach was applied to explore the feasibility of tracking a post-boost rocket from a low earth orbit satellite with real cloud background data. Simulation results show that the PCT/correlation tracking algorithm can perform satisfactorily at signal-to-clutter ratio (SCR) as low as 5 or 7 dB.

  15. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  16. Hearing aid noise suppression and working memory function

    OpenAIRE

    Fischer, Rosa-Linde; Neher, Tobias; Wagener, Kirsten C.

    2017-01-01

    OBJECTIVE: Research findings concerning the relation between benefit from hearing aid (HA) noise suppression and working memory function are inconsistent. The current study thus investigated the effects of three noise suppression algorithms on auditory working memory and the relation with reading span.DESIGN: Using a computer simulation of bilaterally fitted HAs, four settings were tested: (1) unprocessed, (2) directional microphones, (3) single-channel noise reduction and (4) binaural cohere...

  17. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories

    Science.gov (United States)

    Noreen, Saima; O’Connor, Akira R.; MacLeod, Malcolm D.

    2016-01-01

    Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one’s attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC) and the mid-ventrolateral prefrontal cortex (VLPFC) regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think) or to suppress (no-think) the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution). Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex, there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory. PMID:27047412

  18. Netlist Oriented Sensitivity Evaluation (NOSE)

    Science.gov (United States)

    2017-03-01

    published in the interest of scientific and technical information exchange, and its publication does not constitute the Government’s approval or...developing methodologies to assess sensitivities of alternative chip design netlist implementations. The research is somewhat foundational in that such...Netlist-Oriented Sensitivity Evaluation (NOSE) project was to develop methodologies to assess sensitivities of alternative chip design netlist

  19. The suppressive effect of apricot kernel extract on 5alpha-Androst-16-en-3-one generated by microbial metabolism.

    Science.gov (United States)

    Mikoshiba, S; Takenaka, H; Okumura, T; Someya, K; Ohdera, M

    2006-02-01

    Body odours are generated from dead skin cells and secreted materials, such as sweat and sebum, through the metabolism of microorganisms living on the skin. Volatile steroids, key compounds in body odours, are also generated through the metabolism of microorganisms. These volatile steroids strengthen the intensity of the overall body malodour and are sensed differently by males and females. Females are more sensitive than males to volatile steroids, especially 5alpha-androst-16-en-3-one (androstenone). To regulate body odours that are especially unpleasant for women, we devised an androstenone-generation model using the metabolism of Corynebacterium xerosis, which is one of the bacteria living on the axillary skin. Using this model, we studied the suppressive effect of plant extracts on the generation of androstenone. We found that apricot kernel extract (AKE) had the most positive effect among the plant extracts to which we applied the model. However, although AKE did suppress androstenone generation, it did not show any bactericidal effect. Using the cell-free system, AKE also suppressed the generation of androstenone. In conclusion, we found that AKE suppressed the generation of androstenone, which is especially unpleasant for women, and the mechanism was not bactericidal but metabolic inhibition. The results of these studies provide new understanding of the regulation of androstenone, which, in turn, should lead to the development of novel deodorant systems.

  20. Context shapes social judgments of positive emotion suppression and expression.

    Science.gov (United States)

    Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

    2017-02-01

    It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Neutron diagnostics using compton suppression gamma-ray spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, S. P.; Kang, B. S. [Lab. Of Radiation Convergence Science, Dept. of Radiological Science, College of Medical Science, Konyang University, Daejeon (Korea, Republic of); Kim, C. S.; Cheon, M. S.; Cho, S. [National Fusion Research Institute, Daejeon (Korea, Republic of)

    2016-12-15

    Various neutron diagnostic systems such as a fission chamber, stilbene spectrometers, and a neutron activation system (NAS) have been installed at KSTAR for more accurate detection of neutron flux. Among the systems, the NAS is the most reliable and robust tool, and the measurement data of it generally are to be used for calibration of other systems. The Compton suppression gamma-ray spectrometer which can suppress the expected background, noise signal and Compton scattering was used to measure the gamma-rays of neutron activated samples. In this study, the encapsulated indium samples which are installed and irradiated by the neutrons released from the nuclear fusion reactions in the Korea Superconducting Tokamak Advanced Research (KSTAR) was used and measured using Compton suppressed gamma-ray spectrometer to minimize the measurement error. From the experimental results, the statistical error was decreased by Compton suppression system. the statistical error of the measured sample activity in the Compton suppressed system is estimated to be about 2.3 %, and the statistical error of the measured sample activity in the non-suppressed system was estimated to be about 4.9 %. It was found that the system can reduce the measurement error effectively. It is confirmed that this system can be applied to ITER TBM and future nuclear fusion devices.

  2. Automatic arc welding of propulsion system tubing in close proximity to sensitive electronic devices

    Science.gov (United States)

    Lumsden, J. M.; Whittlesey, A. C.

    1981-01-01

    The planned final assembly of the Galileo spacecraft propulsion system tubing, which involves welding in close proximity to sensitive electronics, raised significant concerns about the effects of electromagnetic coupling of weld energy on CMOS and other sensitive integrated circuits. A test program was established to assess the potential of an orbital arc welder and an RF-induction brazing machine to damage sensitive electronic equipment. Test parameters were varied to assess the effectiveness of typical transient suppression practices such as grounding, bonding, and shielding. A technique was developed to calibrate the hazard levels at the victim-circuit location; this technique is described along with the results and conclusions of the test program.

  3. Suppression of pool fires with HRC-125 in a simulated engine nacelle.

    Energy Technology Data Exchange (ETDEWEB)

    Keyser, David R. (INS, Inc., Lexington Park, MD); Hewson, John C.

    2007-06-01

    CFD simulations are conducted to predict the distribution of fire suppressant in an engine nacelle and to predict the suppression of pool fires by the application of this suppressant. In the baseline configuration, which is based on an installed system, suppressant is injected through four nozzles at a rate fast enough to suppress all simulated pool fires. Variations that reduce the mass of the suppression system (reducing the impact of the suppression system on meeting mission needs) are considered, including a reduction in the rate of suppressant injection, a reduction in the mass of suppressant and a reduction in the number of nozzles. In general, these variations should work to reduce the effectiveness of the suppression system, but the CFD results point out certain changes that have negligible impact, at least for the range of phenomena considered here. The results are compared with measurements where available. Comparisons with suppressant measurements are reasonable. A series of twenty-three fire suppression tests were conducted to check the predictions. The pre-test predictions were generally successful in identifying the range of successful suppression tests. In two separate cases, each where one nozzle of the suppression system was capped, the simulation results did indicate a failure to suppress for a condition where the tests indicated successful suppression. When the test-suppressant discharge rate was reduced by roughly 25%, the tests were in agreement with the predictions. That is, the simulations predict a failure to suppress slightly before observed in these cases.

  4. Preliminary evidence for a change in spectral sensitivity of the circadian system at night

    Directory of Open Access Journals (Sweden)

    Parsons Robert H

    2005-12-01

    Full Text Available Abstract Background It is well established that the absolute sensitivity of the suprachiasmatic nucleus to photic stimulation received through the retino-hypothalamic tract changes throughout the 24-hour day. It is also believed that a combination of classical photoreceptors (rods and cones and melanopsin-containing retinal ganglion cells participate in circadian phototransduction, with a spectral sensitivity peaking between 440 and 500 nm. It is still unknown, however, whether the spectral sensitivity of the circadian system also changes throughout the solar day. Reported here is a new study that was designed to determine whether the spectral sensitivity of the circadian retinal phototransduction mechanism, measured through melatonin suppression and iris constriction, varies at night. Methods Human adult males were exposed to a high-pressure mercury lamp [450 lux (170 μW/cm2 at the cornea] and an array of blue light emitting diodes [18 lux (29 μW/cm2 at the cornea] during two nighttime experimental sessions. Both melatonin suppression and iris constriction were measured during and after a one-hour light exposure just after midnight and just before dawn. Results An increase in the percentage of melatonin suppression and an increase in pupil constriction for the mercury source relative to the blue light source at night were found, suggesting a temporal change in the contribution of photoreceptor mechanisms leading to melatonin suppression and, possibly, iris constriction by light in humans. Conclusion The preliminary data presented here suggest a change in the spectral sensitivity of circadian phototransduction mechanisms at two different times of the night. These findings are hypothesized to be the result of a change in the sensitivity of the melanopsin-expressing retinal ganglion cells to light during the night.

  5. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  6. Physical model of lean suppression pressure oscillation phenomena: steam condensation in the light water reactor pressure suppression system (PSS)

    International Nuclear Information System (INIS)

    McCauley, E.W.; Holman, G.S.; Aust, E.; Schwan, H.; Vollbrandt, J.

    1980-01-01

    Using the results of large scale multivent tests conducted by GKSS, a physical model of chugging is developed. The unique combination of accurate digital data and cinematic data has provided the derivation of a detailed, quantified correlation between the dynamic physical variables and the associated two-phase thermo-hydraulic phenomena occurring during lean suppression (chugging) phases of the loss-of-coolant accident in a boiling water reactor pressure suppression system

  7. Stratospheric Airship Design Sensitivity

    Science.gov (United States)

    Smith, Ira Steve; Fortenberry, Michael; Noll, . James; Perry, William

    2012-07-01

    The concept of a stratospheric or high altitude powered platform has been around almost as long as stratospheric free balloons. Airships are defined as Lighter-Than-Air (LTA) vehicles with propulsion and steering systems. Over the past five (5) years there has been an increased interest by the U. S. Department of Defense as well as commercial enterprises in airships at all altitudes. One of these interests is in the area of stratospheric airships. Whereas DoD is primarily interested in things that look down, such platforms offer a platform for science applications, both downward and outward looking. Designing airships to operate in the stratosphere is very challenging due to the extreme high altitude environment. It is significantly different than low altitude airship designs such as observed in the familiar advertising or tourism airships or blimps. The stratospheric airship design is very dependent on the specific application and the particular requirements levied on the vehicle with mass and power limits. The design is a complex iterative process and is sensitive to many factors. In an effort to identify the key factors that have the greatest impacts on the design, a parametric analysis of a simplified airship design has been performed. The results of these studies will be presented.

  8. Extreme sensitivity in Thermoacoustics

    Science.gov (United States)

    Juniper, Matthew

    2017-11-01

    In rocket engines and gas turbines, fluctuations in the heat release rate can lock in to acoustic oscillations and grow catastrophically. Nine decades of engine development have shown that these oscillations are difficult to predict but can usually be eliminated with small ad hoc design changes. The difficulty in prediction arises because the oscillations' growth rate is exceedingly sensitive to parameters that cannot always be measured or simulated reliably, which introduces severe systematic error into thermoacoustic models of engines. Passive control strategies then have to be devised through full scale engine tests, which can be ruinously expensive. For the Apollo F1 engine, for example, 2000 full-scale tests were required. Even today, thermoacoustic oscillations often re-appear unexpectedly at full engine test stage. Although the physics is well known, a novel approach to design is required. In this presentation, the parameters of a thermoacoustic model are inferred from many thousand automated experiments using inverse uncertainty quantification. The adjoint of this model is used to obtain cheaply the gradients of every unstable mode with respect to the model parameters. This gradient information is then used in an optimization algorithm to stabilize every thermoacoustic mode by subtly changing the geometry of the model.

  9. Nonceliac Gluten Sensitivity12

    Science.gov (United States)

    Krigel, Anna; Lebwohl, Benjamin

    2016-01-01

    Nonceliac gluten sensitivity (NCGS) refers to a clinical phenotype in which patients experience intestinal and extraintestinal symptoms related to ingesting a gluten-containing diet after a diagnosis of celiac disease (CD) or wheat allergy has been excluded. CD, an autoimmune disease characterized by villous atrophy triggered by the ingestion of gluten, has increased in prevalence in recent decades, although the majority of patients remain undiagnosed. There is now an increasing public awareness of NCGS and growing interest in the health effects of gluten among health professionals and the lay public. Several randomized controlled trials have explored NCGS but have left many questions unanswered surrounding the pathophysiology, biomarkers, and established diagnostic approach to patients with this condition. Future studies are necessary to establish biomarkers and to elucidate the pathophysiology of this condition because at present, NCGS likely comprises a heterogeneous patient population. In this review, we outline the clinical trials of NCGS as well as the approach to patients with possible NCGS as recommended by an international expert panel. Because maintaining a gluten-free diet has important health, social, and economic consequences, it is necessary for medical professionals to provide practical and evidence-based advice to patients with this condition. PMID:28140327

  10. The measurement and treatment of suppression in amblyopia.

    Science.gov (United States)

    Black, Joanna M; Hess, Robert F; Cooperstock, Jeremy R; To, Long; Thompson, Benjamin

    2012-12-14

    Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%(1-3), the majority of cases being monocular(2). Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation. Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself(4,5) . Amblyopia is characterized by both monocular and binocular deficits(6,7) which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions(8). Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia(9,10) . Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device(11,12) . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which

  11. Sensitivity analysis of groundwater flow

    International Nuclear Information System (INIS)

    Bao Yungbing

    1990-12-01

    A sensitivity analysis of general linear and nonlinear simulation equation sets is developed in this study in order to facilitate the application of the sensitivity analysis to groundwater flow problems. Two methods are considered for the sensitivity calculation: the 'direct method' and the 'adjoint method'. Sensitivity theory was used to establish a sensitivity analysis model for general three dimensional transient groundwater flow. Three different methods for calculation of the sensitivity coefficient are presented. The sensitivity equations and the groundwater flow equations were nummerically solved by the Galerkin finite element method in the model. Sensitivity coefficients were carried out both numerically with the developed direct method and with the known analytic solution. Very good agreement between the two solutions was obtained. The developed sensitivity model was applied to three dimensional (axi-symmetric) groundwater flow in a tunnel system, which was supposed to be located at a depth of 500 meters below the ground surface in a four-layered rock formation. In this case, the sensitivity distribution of the piezometric head was calculated with the direct method and the sensitivity of multiple performance functions to perturbations of the permeability were analysed by using the adjoint method. The calculations results showed that the peaks of the sensitivity coefficients appear mostly in the area around the tunnel. The piezometric head at the studied points (nodes) was quite sensitive to perturbations of the permeability in the layer where the points were located, but practically insensitive to perturbations of the permeability in the bottom layer. The flux into the tunnel and the velocity performance were mostly sensitive to perturbation of the permeability in the layer next to the top layer, but practically insensitive to perturbation of the permeability in the bottom layer. (author)

  12. Microlens Array/Pinhole Mask to Suppress Starlight for Direct Exoplanet Detection

    Science.gov (United States)

    Zimmerman, Neil

    Direct imaging of habitable exoplanets is a key priority of NASA’s Astrophysics roadmap, “Enduring Quests, Daring Visions.” A coronagraphic starlight suppression system situated on a large space telescope offers a viable path to achieving this goal. This type of instrument is central to both the LUVOIR and HabEx mission concepts currently under study for the 2020 Decadal Survey. To directly image an Earth-like exoplanet, an instrument must be sensitive to objects ten billion times dimmer than their parent star. Advanced coronagraphs are designed to modify the shape of the star’s image so that it does not overwhelm the planet's light. Coronagraphs are complex to design and fabricate, tend to sacrifice a significant portion of the exoplanet light entering the telescope, and are highly sensitive to errors in the telescope. The proposed work reduces the demands on the coronagraph and its sensitivity to errors in the telescope, by changing how we implement optics in the spectrograph following the coronagraph. Through optical analysis and modeling, we have found that a microlens array with a specially arranged pattern of pinholes can suppress residual starlight in the scientific image after the coronagraph by more than two orders of magnitude. This added layer of starlight rejection could be used to relax the extreme observatory stability requirements for exo-Earth imaging applications, for example shifting the wavefront stability requirement from a few picometers to a few nanometers. Ultimately this translates to the instrument detecting and spectrally characterizing more exoplanets than a conventional coronagraph system. This microlens/pinhole concept is also compatible with starshadebased starlight suppression systems. The proposed microlens/pinhole device is entirely passive and augments the performance of existing coronagraph designs, while potentially reducing their cost and risk for mission implementation. Our APRA proposal would support a testbed

  13. Arsenite suppression of BMP signaling in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Marjorie A.; Qin, Qin [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States); Hu, Qin; Zhao, Bin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Rice, Robert H., E-mail: rhrice@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States)

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte

  14. Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma

    Directory of Open Access Journals (Sweden)

    Chieh-Ying Kuo

    2017-01-01

    Full Text Available Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

  15. Nonceliac gluten sensitivity.

    Science.gov (United States)

    Fasano, Alessio; Sapone, Anna; Zevallos, Victor; Schuppan, Detlef

    2015-05-01

    During the past decade there has been an impressive increase in popularity of the gluten-free diet (GFD)-now the most trendy alimentary habit in the United States and other countries. According to recent surveys, as many as 100 million Americans will consume gluten-free products within a year. Operating under the concept that the GFD benefits only individuals with celiac disease, health care professionals have struggled to separate the wheat from the chaff; there are claims that eliminating gluten from the diet increases health and helps with weight loss, or even that gluten can be harmful to every human being. However, apart from unfounded trends, a disorder related to ingestion of gluten or gluten-containing cereals, namely nonceliac gluten sensitivity (NCGS), has resurfaced in the literature, fueling a debate on the appropriateness of the GFD for people without celiac disease. Although there is clearly a fad component to the popularity of the GFD, there is also undisputable and increasing evidence for NCGS. However, we require a better understanding of the clinical presentation of NCGS, as well as its pathogenesis, epidemiology, management, and role in conditions such as irritable bowel syndrome, chronic fatigue, and autoimmunity. Before we can begin to identify and manage NCGS, there must be agreement on the nomenclature and definition of the disorder based on proper peer-reviewed scientific information. We review the most recent findings on NCGS and outline directions to dissipate some of the confusion related to this disorder. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Probiotics, prebiotics, synbiotics and insulin sensitivity.

    Science.gov (United States)

    Kim, Y A; Keogh, J B; Clifton, P M

    2017-10-17

    Animal studies indicate that the composition of gut microbiota may be involved in the progression of insulin resistance to type 2 diabetes. Probiotics and/or prebiotics could be a promising approach to improve insulin sensitivity by favourably modifying the composition of the gut microbial community, reducing intestinal endotoxin concentrations and decreasing energy harvest. The aim of the present review was to investigate the effects of probiotics, prebiotics and synbiotics (a combination of probiotics and prebiotics) on insulin resistance in human clinical trials and to discuss the potential mechanisms whereby probiotics and prebiotics improve glucose metabolism. The anti-diabetic effects of probiotics include reducing pro-inflammatory cytokines via a NF-κB pathway, reduced intestinal permeability, and lowered oxidative stress. SCFA play a key role in glucose homeostasis through multiple potential mechanisms of action. Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release of glucagon-like peptide-1 and peptide YY resulting in increased insulin and decreased glucagon secretion, and suppressed appetite. SCFA can decrease intestinal permeability and decrease circulating endotoxins, lowering inflammation and oxidative stress. SCFA may also have anti-lipolytic activities in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation of 5'-AMP-activated protein kinase signalling in muscle and liver tissues. Resistant starch and synbiotics appear to have favourable anti-diabetic effects. However, there are few human interventions. Further well-designed human clinical studies are required to develop recommendations for the prevention of type 2 diabetes with pro- and prebiotics.

  17. The group delay and suppression pattern of the cochlear microphonic potential recorded at the round window.

    Directory of Open Access Journals (Sweden)

    Wenxuan He

    Full Text Available BACKGROUND: It is commonly assumed that the cochlear microphonic potential (CM recorded from the round window (RW is generated at the cochlear base. Based on this assumption, the low-frequency RW CM has been measured for evaluating the integrity of mechanoelectrical transduction of outer hair cells at the cochlear base and for studying sound propagation inside the cochlea. However, the group delay and the origin of the low-frequency RW CM have not been demonstrated experimentally. METHODOLOGY/PRINCIPAL FINDINGS: This study quantified the intra-cochlear group delay of the RW CM by measuring RW CM and vibrations at the stapes and basilar membrane in gerbils. At low sound levels, the RW CM showed a significant group delay and a nonlinear growth at frequencies below 2 kHz. However, at high sound levels or at frequencies above 2 kHz, the RW CM magnitude increased proportionally with sound pressure, and the CM phase in respect to the stapes showed no significant group delay. After the local application of tetrodotoxin the RW CM below 2 kHz became linear and showed a negligible group delay. In contrast to RW CM phase, the BM vibration measured at location ∼2.5 mm from the base showed high sensitivity, sharp tuning, and nonlinearity with a frequency-dependent group delay. At low or intermediate sound levels, low-frequency RW CMs were suppressed by an additional tone near the probe-tone frequency while, at high sound levels, they were partially suppressed only at high frequencies. CONCLUSIONS/SIGNIFICANCE: We conclude that the group delay of the RW CM provides no temporal information on the wave propagation inside the cochlea, and that significant group delay of low-frequency CMs results from the auditory nerve neurophonic potential. Suppression data demonstrate that the generation site of the low-frequency RW CM shifts from apex to base as the probe-tone level increases.

  18. Suppressive effects of thermal-treated oyster shells on cadmium and copper translocation in maize plants.

    Science.gov (United States)

    Wang, Chunyan; Alidoust, Darioush; Isoda, Akihiro; Li, Maosong

    2017-08-01

    The effect of varied concentrations of thermal-treated oyster shells (TOS) on the suppression of cadmium (Cd) and copper (Cu) uptake and translocation into the shoots of maize plants was examined. Maize plants were grown in Cd- and Cu-contaminated Andosol for 70 days. The concentration of mobile Cd (extracted with 1 M NH 4 NO 3 ) decreased with increasing TOS applications, whereas an increase in the concentration of mobile Cu in soil resulted from cumulative TOS additions. The addition of 2% TOS had no prohibitive effects on Cd uptake in maize shoots, but the 4 and 8% TOS treatments decreased Cd accumulation in shoots by 41 and 59%, respectively. The possible mechanisms underlying Cd suppression in maize shoots were the enhanced Cd adsorption caused by pH-induced increases in the negative charge of the soil and the antagonistic effects of Ca resulting from competition for exchange sites at the root surface. Cu accumulation in maize shoots increased by 34, 51, and 53% with the addition of 2, 4, and 8% TOS, respectively, but this increase was not observed for Cd accumulation. These results suggested that, in multi-metal-contaminated soils, attention should be paid to the potential mobility of target metals and the pH of the contaminated soil. From a plant physiological perspective, contaminated soils slightly reduced photosynthetic performance. However, the addition of TOS to the soil at levels higher than 4% substantially decreased photosynthetic performance, indicating that CaO-based suppressants at critical loads might damage the net photosynthetic rates of sensitive maize plants.

  19. TCDD adsorbed on silica as a model for TCDD contaminated soils: Evidence for suppression of humoral immunity in mice.

    Science.gov (United States)

    Kaplan, Barbara L F; Crawford, Robert B; Kovalova, Natalia; Arencibia, Amaya; Kim, Seong Su; Pinnavaia, Thomas J; Boyd, Stephen A; Teppen, Brian J; Kaminski, Norbert E

    2011-04-11

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the prototypical aryl hydrocarbon receptor (AhR) ligand, exhibits immune suppression in vivo and in vitro. Suppression of primary humoral immune responses in particular has been well characterized as one of the most sensitive functional immune endpoints in animals treated with TCDD. Previous studies have used purified TCDD to elucidate the mechanisms by which TCDD and dioxin-like compounds (DLC) impair IgM production by B cells, but did not represent the route by which animals and humans are likely to be exposed environmentally. In the studies reported here, mice were treated with TCDD adsorbed onto a well-defined synthetic silica phase of known purity and physical properties, followed by sensitization with sheep erythrocytes to initiate a humoral immune response. We found that surfactant-templated mesoporous forms of amorphous silica provided an ideal combination of purity, dispersibility and textural properties for immobilizing TCDD. TCDD-adsorbed silica distributed to the spleen and liver after oral administration as assessed by induction of cyp1a1 gene expression. Most notably, TCDD delivered in the adsorbed state on amorphous silica and as a solute in corn oil (CO) produced similar suppression of the anti-sheep red blood cell immunoglobulin M antibody forming cell (sRBC IgM AFC) response at equivalent doses of TCDD. These results suggest that TCDD immobilized on silicate particles found in soils distributes to the spleen and suppresses humoral immunity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. A TOUCH-SENSITIVE DEVICE

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to an optical touch-sensitive device and a method of determining a position and determining a position change of an object contacting an optical touch sensitive device. In particular, the present invention relates to an optical touch pad and a method of determining...... a position and determining a position change of an object contacting an optical touch pad. A touch-sensitive device, according to the present invention may comprise a light source, a touch- sensitive waveguide, a detector array, and a first light redirecting member, wherein at least a part of the light...... propagating towards a specific point of the detector array is prevented from being incident upon the specific point of the detector array when an object contacts a touch-sensitive surface of the touch-sensitive waveguide at a corresponding specific contact point....