Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

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Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

2008-02-01

We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

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Zhiyong Wang

2017-01-01

Full Text Available Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP, a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI. The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.

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Aman, Urooj; Subhan, Fazal; Shahid, Muhammad; Akbar, Shehla; Ahmad, Nisar; Ali, Gowhar; Fawad, Khwaja; Sewell, Robert D E

2016-02-24

Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI

TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

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Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

2011-01-01

In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats.

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Lee, Ji-Hye; Li, Dong Xing; Yoon, Heera; Go, Donghyun; Quan, Fu Shi; Min, Byung-Il; Kim, Sun Kwang

2014-12-06

Oxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats. The behavioral signs of cold allodynia in Sprague-Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment. The serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 μg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 μg, i.t.) or

Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

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Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

2010-01-01

Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion.

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Jesse, Cristiano R; Wilhelm, Ethel A; Nogueira, Cristina W

2010-12-01

Neuropathic pain is associated with significant co-morbidities, including depression, which impact considerably on the overall patient experience. Pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. Neuropathic pain is characterized by hyperexcitability within nociceptive pathways and remains difficult to treat with standard analgesics. The present study determined the effect of bis selenide and conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on neuropathic pain using mechanical allodynic and on depressive-like behavior. Male mice were subjected to chronic constriction injury (CCI) or sham surgery and were assessed on day 14 after operation. Mice received oral treatment with bis selenide (1-5 mg/kg), fluoxetine, amitriptyline, or bupropion (10-30 mg/kg). The response frequency to mechanical allodynia in mice was measured with von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for depression-like behavior. The CCI procedure produced mechanical allodynia and increased depressive-like behavior in the FST. All of the drugs produced antiallodynic effects in CCI mice and produced antidepressant effects in control mice without altering locomotor activity. In CCI animals, however, only the amitriptyline and bis selenide treatments significantly reduced immobility in the FST. These data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide and amitriptyline but not by the conventional antidepressants fluoxetine and buproprion. Bis selenide was more potent than the other drugs tested for antidepressant-like and antiallodynic effects in mice.

Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

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Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

2017-02-01

Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice.

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Cooper, Michael A; Menta, Blaise W; Perez-Sanchez, Consuelo; Jack, Megan M; Khan, Zair W; Ryals, Janelle M; Winter, Michelle; Wright, Douglas E

2018-08-01

Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction. Published by Elsevier Inc.

Upregulation of EMMPRIN (OX47 in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

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Qun Wang

2015-01-01

Full Text Available Matrix metalloproteinases (MMPs are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR, and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators.

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Wieseler, Julie; Ellis, Amanda; McFadden, Andrew; Stone, Kendra; Brown, Kimberley; Cady, Sara; Bastos, Leandro F; Sprunger, David; Rezvani, Niloofar; Johnson, Kirk; Rice, Kenner C; Maier, Steven F; Watkins, Linda R

2017-06-01

Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown. Here we tested if trigeminal nucleus caudalis (Sp5C) glial and/or immune cells are activated following supradural inflammatory soup, and if putative glial/immune inhibitors suppress the consequent facial allodynia. Inflammatory soup was administered via bilateral indwelling supradural catheters in freely moving rats, inducing robust and reliable facial allodynia. Gene expression for microglial/macrophage activation markers, interleukin-1β, and tumor necrosis factor-α increased following inflammatory soup along with robust expression of facial allodynia. This provided the basis for pursuing studies of the behavioral effects of 3 diverse immunomodulatory drugs on facial allodynia. Pretreatment with either of two compounds broadly used as putative glial/immune inhibitors (minocycline, ibudilast) prevented the development of facial allodynia, as did treatment after supradural inflammatory soup but prior to the expression of facial allodynia. Lastly, the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone likewise blocked development of facial allodynia after supradural inflammatory soup. Taken together, these exploratory data support that activated glia and/or immune cells may drive the development of facial allodynia in response to supradural inflammatory soup in unanesthetized male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

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Shi J

2016-11-01

Full Text Available Jinshan Shi,1,* Ke Jiang,2,* Zhaoduan Li,3 1Department of Anesthesiology, Guizhou Provincial People’s Hospital, 2Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 3Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1 in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes. Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1

Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats

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Suk-Yun Kang

2012-01-01

Full Text Available Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV reduced cold allodynia in sciatic nerve chronic constriction injury (CCI rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist, but not prazosin (α1-adrenoceptor antagonist or propranolol (nonselective β-adrenoceptor antagonist. In addition, coadministration of low-dose DBV (0.25 mg/kg and intrathecal clonidine (α2-adrenoceptor agonist synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

Low Frequency Electroacupuncture Alleviated Spinal Nerve Ligation Induced Mechanical Allodynia by Inhibiting TRPV1 Upregulation in Ipsilateral Undamaged Dorsal Root Ganglia in Rats

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Yong-Liang Jiang

2013-01-01

Full Text Available Neuropathic pain is an intractable problem in clinical practice. Accumulating evidence shows that electroacupuncture (EA with low frequency can effectively relieve neuropathic pain. Transient receptor potential vanilloid type 1 (TRPV1 plays a key role in neuropathic pain. The study aimed to investigate whether neuropathic pain relieved by EA administration correlates with TRPV1 inhibition. Neuropathic pain was induced by right L5 spinal nerve ligation (SNL in rats. 2 Hz EA stimulation was administered. SNL induced mechanical allodynia in ipsilateral hind paw. SNL caused a significant reduction of TRPV1 expression in ipsilateral L5 dorsal root ganglia (DRG, but a significant up-regulation in ipsilateral L4 and L6 DRGs. Calcitonin gene-related peptide (CGRP change was consistent with that of TRPV1. EA alleviated mechanical allodynia, and inhibited TRPV1 and CGRP overexpressions in ipsilateral L4 and L6 DRGs. SNL did not decrease pain threshold of contralateral hind paw, and TRPV1 expression was not changed in contralateral L5 DRG. 0.001, 0.01 mg/kg TRPV1 agonist 6′-IRTX fully blocked EA analgesia in ipsilateral hind paw. 0.01 mg/kg 6′-IRTX also significantly decreased pain threshold of contralateral paw. These results indicated that inhibition of TRPV1 up-regulation in ipsilateral adjacent undamaged DRGs contributed to low frequency EA analgesia for mechanical allodynia induced by spinal nerve ligation.

Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

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Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

2016-01-01

The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Cold allodynia and

Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

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Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2016-12-01

We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats

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Xu Wen

2010-08-01

Full Text Available Abstract Background Temporomandibular disorders (TMDs are characterized by persistent orofacial pain and have diverse etiologic factors that are not well understood. It is thought that central sensitization leads to neuronal hyperexcitability and contributes to hyperalgesia and spontaneous pain. Nonsteroidal anti-inflammatory drugs (NSAIDs are currently the first choice of drug to relieve TMD pain. NSAIDS were shown to exhibit anticonvulsant properties and suppress cortical neuron activities by enhancing neuronal voltage-gated potassium KCNQ/Kv7 channels (M-current, suggesting that specific activation of M-current might be beneficial for TMD pain. Results In this study, we selected a new anticonvulsant drug retigabine that specifically activates M-current, and investigated the effect of retigabine on inflammation of the temporomandibular joint (TMJ induced by complete Freund's adjuvant (CFA in rats. The results show that the head withdrawal threshold for escape from mechanical stimulation applied to facial skin over the TMJ in inflamed rats was significantly lower than that in control rats. Administration of centrally acting M-channel opener retigabine (2.5 and 7.5 mg/kg can dose-dependently raise the head withdrawal threshold of mechanical allodynia, and this analgesic effect can be reversed by the specific KCNQ channel blocker XE991 (3 mg/kg. Food intake is known to be negatively associated with TMJ inflammation. Food intake was increased significantly by the administration of retigabine (2.5 and 7.5 mg/kg, and this effect was reversed by XE991 (3 mg/kg. Furthermore, intracerebralventricular injection of retigabine further confirmed the analgesic effect of central retigabine on inflammatory TMJ. Conclusions Our findings indicate that central sensitization is involved in inflammatory TMJ pain and pharmacological intervention for controlling central hyperexcitability by activation of neuronal KCNQ/M-channels may have therapeutic potential for

Low-threshold mechanoreceptors play a frequency-dependent dual role in subjective ratings of mechanical allodynia.

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Löken, Line S; Duff, Eugene P; Tracey, Irene

2017-12-01

In the setting of injury, myelinated primary afferent fibers that normally signal light touch are thought to switch modality and instead signal pain. In the absence of injury, touch is perceived as more intense when firing rates of Aβ afferents increase. However, it is not known if varying the firing rates of Aβ afferents have any consequence to the perception of dynamic mechanical allodynia (DMA). We hypothesized that, in the setting of injury, the unpleasantness of DMA would be intensified as the firing rates of Aβ afferents increase. Using a stimulus-response protocol established in normal skin, where an increase in brush velocity results in an increase of Aβ afferent firing rates, we tested if brush velocity modulated the unpleasantness of capsaicin-induced DMA. We analyzed how changes in estimated low-threshold mechanoreceptor firing activity influenced perception and brain activity (functional MRI) of DMA. Brushing on normal skin was perceived as pleasant, but brushing on sensitized skin produced both painful and pleasant sensations. Surprisingly, there was an inverse relationship between Aβ firing rates and unpleasantness such that brush stimuli that produced low firing rates were most painful and those that elicited high firing rates were rated as pleasant. Concurrently to this, we found increased cortical activity in response to low Aβ firing rates in regions previously implicated in pain processing during brushing of sensitized skin, but not normal skin. We suggest that Aβ signals do not merely switch modality to signal pain during injury. Instead, they exert a high- and low-frequency-dependent dual role in the injured state, with respectively both pleasant and unpleasant consequences. NEW & NOTEWORTHY We suggest that Aβ signals do not simply switch modality to signal pain during injury but play a frequency-dependent and dual role in the injured state with both pleasant and unpleasant consequences. These results provide a framework to resolve the

Contact lenses, migraine, and allodynia

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Ozgur Bulent Timucin

2016-01-01

Full Text Available Clinical trials and electrophysiologic studies demonstrated increased perceptual sensitivity in patients suffering from migraines. At least, one triggering factor is described in 85% of migraine patients. The aim of this report was to investigate the relationship between contact lens (CL usage and migraine attacks in two cases. Two patients who were diagnosed with migraine reported that the frequency of migraine attacks increased after they switched to using CL with different base curves (BCs. These two patients, who began using CL with different BCs experienced discomfort and dryness of the eye. The ocular complaints were followed by migraine attacks. CL intolerance was also developed during migraine attack in one of the cases. The frequency of migraine attacks decreased and allodynia relieved significantly when flatter BCs were selected. CL related stimulus could have triggered the migraine attack. CLs should be well fitted in migraine patients with allodynia.

Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain.

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Kupers, R; Yu, W; Persson, J K; Xu, X J; Wiesenfeld-Hallin, Z

1998-05-01

Sensory abnormalities and changes in spontaneous behavior were examined after a photochemically induced ischemic lesion of the rat sciatic nerve. Male adult rats were anesthetized and the sciatic nerve was exposed. After the intravenous injection of a photosensitizing dye, erythrosin B, the exposed nerve was irradiated just proximal to the nerve trifurcation with light from an argon laser. Three different irradiation times were used, 30 s, 1 and 2 min. In sham-operated rats, the exposed sciatic nerve was irradiated for 2 min without prior injection of the erythrosin B. Rats were tested for the presence of mechanical, cold and heat allodynia or hyperalgesia. All the animals in the 1- and 2-min irradiation groups developed mechanical, cold and heat allodynia after nerve irradiation. A significant dose-dependent effect of laser exposure time was observed for all modalities tested (2 min > 1 min > 30 s = sham). The maximum effects were observed at 3 and 7 days postirradiation and remained present for up to 10 weeks. No significant contralateral effects were observed in any of the groups. In three separate groups of rats (1, 2 and 4 min of laser exposure), the presence of possible signs of spontaneous pain (paw shaking, paw elevation and freezing behavior) was tested. A significant and exposure time-dependent increase in spontaneous paw elevation and paw shaking was observed which was maximal at week 1, but resolved at 4 weeks (4 min > 2 min > 1 min > sham). In addition, animals in all ischemic groups, but not in the sham group, showed a significant increase in freezing behavior up to 4 weeks after nerve irradiation. Light microscopic evaluation of nerves removed 7 days post-irradiation, i.e. when maximal allodynia was observed, showed clear evidence of demyelination of large myelinated fibers. These data indicate that photochemically-induced peripheral nerve ischemia is associated with abnormal pain-related behaviors, including mechanical, thermal and cold allodynia

Constriction of the buccal branch of the facial nerve produces unilateral craniofacial allodynia.

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Lewis, Susannah S; Grace, Peter M; Hutchinson, Mark R; Maier, Steven F; Watkins, Linda R

2017-08-01

Despite pain being a sensory experience, studies of spinal cord ventral root damage have demonstrated that motor neuron injury can induce neuropathic pain. Whether injury of cranial motor nerves can also produce nociceptive hypersensitivity has not been addressed. Herein, we demonstrate that chronic constriction injury (CCI) of the buccal branch of the facial nerve results in long-lasting, unilateral allodynia in the rat. An anterograde and retrograde tracer (3000MW tetramethylrhodamine-conjugated dextran) was not transported to the trigeminal ganglion when applied to the injury site, but was transported to the facial nucleus, indicating that this nerve branch is not composed of trigeminal sensory neurons. Finally, intracisterna magna injection of interleukin-1 (IL-1) receptor antagonist reversed allodynia, implicating the pro-inflammatory cytokine IL-1 in the maintenance of neuropathic pain induced by facial nerve CCI. These data extend the prior evidence that selective injury to motor axons can enhance pain to supraspinal circuits by demonstrating that injury of a facial nerve with predominantly motor axons is sufficient for neuropathic pain, and that the resultant pain has a neuroimmune component. Copyright © 2016 Elsevier Inc. All rights reserved.

Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

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Golam Mustafa

2017-01-01

Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

Repetitive Acupuncture Point Treatment with Diluted Bee Venom Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced Neuropathic Mice.

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Yeo, Ji-Hee; Yoon, Seo-Yeon; Kwon, Soon-Keun; Kim, Sol-Ji; Lee, Jang-Hern; Beitz, Alvin J; Roh, Dae-Hyun

2016-03-01

The chemotherapeutic agent, oxaliplatin, produces a robust painful neuropathy that results in the loss of intraepidermal nerve fibers (IENFs). We have previously reported that an acupuncture point (acupoint) injection of diluted bee venom (DBV) produces a temporary antiallodynic effect in oxaliplatin-induced neuropathic mice. Herein we show a significant long-lasting antinociceptive effect of repetitive DBV acupoint treatment on oxaliplatin-induced mechanical allodynia and a significant reduction in the loss of IENFs. DBV (0.1 mg/kg, subcutaneous) was administered once a day for 18 days beginning on day 15 after oxaliplatin injection. Immunohistochemistry for IENF was performed on the glabrous skin of the hind paw footpad using the pan-neuronal marker, protein gene product 9.5. A temporary increase in mechanical threshold was observed 60 minutes after a single DBV injection into the Zusanli acupoint, and this effect was enhanced over time with repetitive DBV treatments. The basal mechanical threshold before daily DBV injection also increased from day 7 after DBV injections, and peaked at day 14 after DBV treatment. Moreover, the oxaliplatin-induced loss of IENFs was significantly reduced in mice treated repetitively with DBV. Repetitive pretreatment with the α-2 adrenoceptor antagonist, yohimbine, (5 mg/kg, subcutaneous) completely prevented the antiallodynic effects and the increase in IENFs observed in mice treated repetitively with DBV. We showed that repetitive acupoint stimulation with DBV gradually and significantly reduced oxaliplatin-induced mechanical allodynia and restored the loss of IENFs in neuropathic mice via an α-2 adrenoceptor mechanism. Collectively, results of this study suggest that repetitive acupoint treatment with DBV can be a potential strategy for the management of chemotherapy-induced neuropathy. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

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Bahar, Muh. Akbar; Andoh, Tsugunobu; Ogura, Keisuke; Hayakawa, Yoshihiro; Saiki, Ikuo; Kuraishi, Yasushi

2013-01-01

Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation) ...

Prevention of Paclitaxel-induced allodynia by Minocycline: Effect on loss of peripheral nerve fibers and infiltration of macrophages in rats

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Xin Wen-Jun

2010-11-01

Full Text Available Abstract Background Although paclitaxel is a frontline antineoplastic agent for treatment of solid tumors, the paclitaxel-evoked pain syndrome is a serious problem for patients. There is currently no valid drug to prevent or treat the paclitaxel-induced allodynia, partly due to lack of understanding regarding the cellular mechanism. Studies have shown that minocycline, an inhibitor of microglia/macrophage, prevented neuropathic pain and promoted neuronal survival in animal models of neurodegenerative disease. Recently, Cata et al also reported that minocycline inhibited allodynia induced by low-dose paclitaxel (2 mg/kg in rats, but the mechanism is still unclear. Results Here, we investigate by immunohistochemistry the change of intraepidermal nerve fiber (IENF in the hind paw glabrous skin, expression of macrophage and activating transcription factor 3 (ATF3 in DRG at different time points after moderate-dose paclitaxel treatment (cumulative dose 24 mg/kg; 3 × 8 mg/kg in rats. Moreover, we observe the effect of minocycline on the IENF, macrophages and ATF3. The results showed that moderate-dose paclitaxel induced a persisted, gradual mechanical allodynia, which was accompanied by the loss of IENF in the hind paw glabrous skin and up-regulation of macrophages and ATF3 in DRG in rats. The expressions of ATF3 mainly focus on the NF200-positive cells. More importantly, we observed that pretreatment of minocycline at dose of 30 mg/kg or 50 mg/kg, but not 5 mg/kg, prevented paclitaxel-evoked allodynia. The evidence from immunohistochemistry showed that 30 mg/kg minocycline rescued the degeneration of IENF, attenuated infiltration of macrophages and up-regulation of ATF3 induced by paclitaxel treatment in rats. Conclusions Minocycline prevents paclitaxel-evoked allodynia, likely due to its inhibition on loss of IENF, infiltration of macrophages and up-regulation of ATF3 in rats. The finding might provide potential target for preventing paclitaxel

Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

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Woolf Clifford J

2005-12-01

Full Text Available Abstract Background Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia. To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.

Further evidence of emotional allodynia in unmedicated young adults with major depressive disorder.

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Alexander Ushinsky

Full Text Available Recent evidence suggests that sensitivity to the emotional sequela of experimental thermal pain(measured by emotional unpleasantness is heightened in individuals with major depressive disorder(MDD, a phenomenon we termed "emotional allodynia". The aim of this study was to examine whether acute happy and sad mood induction alters emotional allodynia in MDD. We hypothesized that emotional allodynia will be a robust characteristic of individuals with MDD compared to healthy controls. Thus, it would remain following acute mood induction, independent of valence.Twenty-one subjects with current MDD and 21 well-matched healthy subjects(HC received graded brief temperature stimuli following happy and sad mood inductions procedures(MIP. All subjects rated the intensity and affect(pleasantness/unpleasantness of each stimulus. Sensory(pain intensity and affective(pain unpleasantness thresholds were determined by methods of constant stimuli.The MIPs reliably induced happy and sad mood and the resulting induced mood and subjective arousal were not different between the groups at the time of temperature stimulation. Compared to HC, MDD individuals demonstrated emotional allodynia. We found significantly decreased affective pain thresholds whereby significantly lower temperatures became unpleasant in the MDD compared to the HC group. This was not observed for the sensory pain thresholds. Within the MDD, the affective pain thresholds were significantly lower than the corresponding pain intensity thresholds, whereby non-painful temperatures were already unpleasant for the MDD irrespective of the induced mood. This was not observed for the HC groups where the affective and pain intensity thresholds were comparable.These findings suggest that emotional allodynia may be a chronic characteristic of current MDD. Future studies should determine if emotional allodynia persists after psychological or pharmacological interventions. Finally, longitudinal work should

Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

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Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

2017-07-01

In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (bee venom, complete Freud's adjuvant.

Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats

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Castel A

2013-12-01

Full Text Available Aude Castel, Pascal VachonFaculty of Veterinary Medicine, Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, QC, CanadaPurpose: The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP, amitriptyline (AMI, and carbamazepine (CARBA for the treatment of a rodent central neuropathic pain model.Methods: Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug.Results: A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05. AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant.Conclusion: Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA.Keywords: central pain, thalamus, amitriptyline, carbamazepine

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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Alireza Abed

2017-11-01

Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Magnetization reversal mechanisms under oblique magnetic fields

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Ntallis, N.; Efthimiadis, K.G., E-mail: kge@auth.gr

2017-03-01

In this work finite element micromagnetic simulations were performed in order to study the reversal mechanisms of spherical ferromagnetic particles with uniaxial magnetocrystalline anisotropy, when they are magnetized along an oblique direction with respect to the anisotropy axis. Magnetization loops are taken in different directions of external magnetic field, at different anisotropy constants and particle sizes. In the simulation results, the three reversal mechanisms (coherent, curling and domains) are observed and new phenomena arise due to the action of oblique magnetic fields. Moreover, the dependence of the critical fields with respect to the angle of the external field is presented. - Highlights: • Finite element micromagnetic simulation of the three different reversal mechanisms. • For the curling mechanism, the new phenomenon is the rotation of the vortex. • In the domain reversal mechanism, the formed domain wall is smaller than 180°. • In soft ferromagnetic particles a rearrangement of the magnetic domains is observed.

Clinical evidence of parietal cortex dysfunction and correlation with extent of allodynia in CRPS type 1.

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Cohen, H; McCabe, C; Harris, N; Hall, J; Lewis, J; Blake, D R

2013-04-01

Unusual symptoms such as digit misidentification and neglect-like phenomena have been reported in complex regional pain syndrome (CRPS), which we hypothesized could be explained by parietal lobe dysfunction. Twenty-two patients with chronic CRPS attending an in-patient rehabilitation programme underwent standard neurological examination followed by clinical assessment of parietal lobe function and detailed sensory testing. Fifteen (68%) patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six or more test categories and demonstrated new clinical signs consistent with their parietal testing impairments, which were impacting significantly on activities of daily living. A higher incidence was noted in subjects with >1 limb involvement, CRPS affecting the dominant side and in left-handed subjects. Eighteen patients (82%) had mechanical allodynia covering 3-57.5% of the body surface area. Allochiria (unilateral tactile stimulation perceived only in the analogous location on the opposite limb), sensory extinction (concurrent bilateral tactile stimulation perceived only in one limb), referred sensations (unilateral tactile stimulation perceived concurrently in another discrete body area) and dysynchiria (unilateral non-noxious tactile stimulation perceived bilaterally as noxious) were present in some patients. Greater extent of body surface allodynia was correlated with worse parietal function (Spearman's rho = -0.674, p = 0.001). In patients with chronic CRPS, detailed clinical examination may reveal parietal dysfunction, with severity relating to the extent of allodynia. © 2012 European Federation of International Association for the Study of Pain Chapters.

Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.

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Tian, Jie; Gu, Yiwen; Su, Diansan; Wu, Yichao; Wang, Xiangrui

2009-02-01

The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

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Ya-Qun Zhou

2018-04-01

Full Text Available Cancer-induced bone pain (CIBP is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100 mg/kg and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200 mg/kg significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord. Keywords: Cancer-induced bone pain, Reactive oxygen species, PBN, Tempol

Peripheral Neuropathic Pain: A mechanism-related organizing principle based on sensory profiles

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Baron, Ralf; Maier, Christoph; Attal, Nadine

2017-01-01

with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed...

Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

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Shigeo Hasegawa

Full Text Available BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2 (cPLA(2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2 activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha and interleukin-1beta (IL-1beta expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

Concomitant Migraine and Temporomandibular Disorders are Associated With Higher Heat Pain Hyperalgesia and Cephalic Cutaneous Allodynia.

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Chaves, Thais C; Dach, Fabíola; Florencio, Lidiane L; Carvalho, Gabriela F; Gonçalves, Maria C; Bigal, Marcelo E; Speciali, José G; Bevilaqua-Grossi, Débora

2016-10-01

The aim of this study was to assess differences in the levels of hyperalgesia and cutaneous allodynia (CA) among women with migraine, temporomandibular disorders (TMD), or both. Eighty women participated in the study. Mean ages for the control group, TMD group, migraine group, and migraine+TMD group were 26.15 (95% confidence interval [CI], 28.73 to 23.57), 31.65 (95% CI, 37.82 to 25.48), 35.05 (95% CI, 40.37 to 29.73), and 34.20 (95% CI, 37.99 to 30.41) years, respectively. The 12-item Allodynia Symptom Checklist was administered to assess CA. All participants underwent the Quantitative Sensory Test to determine the cold-pain and heat-pain thresholds. Mechanical pain thresholds were assessed using Semmes-Weinstein monofilaments. One-way analysis of variance and χ tests were used for statistical analysis. Alpha was set at 0.05 level for statistical significance. For all sites evaluated, the mean cold-pain threshold values were significantly lower in the TMD, migraine, and TMD+migraine groups compared with the control group. However, the mean heat-pain threshold values in the extracephalic region were significantly smaller only for the TMD+migraine group compared with the control group (41.94°C; 95% CI, 40.54 to 43.34 vs. 44.79°C; 95% CI, 43.45 to 46.12; P=0.03). Mechanical hyperalgesia in orofacial and neck sites was significantly lower in the TMD and TMD+migraine groups compared with the control group. Mean total 12-item Allodynia Symptom Checklist score in the TMD+migraine group was significantly higher than in the migraine group (9.53; 95% CI, 7.45 to 11.60 vs. 6.95; 95% CI, 5.35 to 8.55; P=0.02). More pronounced levels of hyperalgesia and CA were found in patients with both TMD and migraine. Thus, it is suggested that the concomitant presence of TMD and migraine may be related to intensification of central sensitization.

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury

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Ellis, Amanda; Grace, Peter M.; Wieseler, Julie; Favret, Jacob; Springer, Kendra; Skarda, Bryce; Hutchinson, Mark R.; Falci, Scott; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

2016-01-01

Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 hr after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1β, and NLRP3, as well as IL-1β protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury. PMID:27519154

Spinal cord transection-induced allodynia in rats--behavioral, physiopathological and pharmacological characterization.

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Saïd M'Dahoma

Full Text Available In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i mechanical and thermal sensory alterations, (ii responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT. SCT was performed at thoracic T8-T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm2 cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT- versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury and glial activation markers (OX-42, GFAP, P2×4, P2×7, TLR4 was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1β, IL-6 and TNF-α were also markedly but differentially up-regulated at T6-T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p., morphine (3-10 mg/kg s.c. and tapentadol (10-20 mg/kg i.p. significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study.

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Lipton, Richard B; Munjal, Sagar; Buse, Dawn C; Bennett, Alix; Fanning, Kristina M; Burstein, Rami; Reed, Michael L

2017-07-01

In a population sample of persons with migraine treating with a single category of acute migraine medication, to identify rates and factors associated with acute treatment outcomes, including 2-hour pain freedom (2hPF), 24-hour pain response (24hPR), and 24-hour sustained pain response (24hSPR). Key predictors include acute treatment type (triptans and other medication categories), the influence of allodynia on response to medication, and the interaction between medication category and presence of allodynia in response to treatment among people with migraine. Cutaneous allodynia was previously associated with inadequate 2hPF, 24hPR, and 24hSPR (sustained response at 24 hours among those with adequate 2hPF) among people with migraine in the American Migraine Prevalence and Prevention (AMPP) Study. The AMPP Study obtained data from a representative US sample of persons with migraine by mailed questionnaire. The 2006 survey included 8233 people with migraine aged 18 or over who completed the Migraine Treatment Optimization Questionnaire (mTOQ). mTOQ was used to assess acute treatment outcomes including 2hPF, 24hPR, and 24hSPR. Eligible individuals used only a single category of acute prescription migraine treatments (n  =  5236, 63.6%). This sample was stratified into 5 categories of type of acute prescription headache medication used (triptans, nonsteroidal anti-inflammatory drugs, barbiturate-combinations, opioids, and opioid combinations and ergot alkaloids). Separate binary logistic regression models evaluated: (1) triptans vs other medication types; (2) presence of allodynia vs no allodynia; and (3) the interaction of medication category with allodynia. Sociodemographic variables, health insurance status, over-the-counter and preventive medication use were included as covariates. Odds ratios (OR) and 95% confidence intervals (CI) were generated for each acute treatment outcome. Among eligible participants, the mean age was 46 years, and 82.5% were women

The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy

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Deng Liting

2012-09-01

Full Text Available Abstract Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel. A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4 signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p. suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p., but not the CB1 antagonist AM251 (3 mg/kg i.p., consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p. failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.

Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study

OpenAIRE

Keizer, D.; van Wijhe, M.; Post, W.J.; Uges, D.R.A.; Wierda, J.M.K.H.

2007-01-01

Background: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with p...

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

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Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study

NARCIS (Netherlands)

Keizer, D.; van Wijhe, M.; Post, W.J.; Uges, D.R.A.; Wierda, J.M.K.H.

Background: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical

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.

Presurgical ketoprofen, but not morphine, dipyrone, diclofenac or tenoxicam, preempts post-incisional mechanical allodynia in rats

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Prado W.A.

2002-01-01

Full Text Available The treatment of pain before it initiates may prevent the persistent pain-induced changes in the central nervous system that amplify pain long after the initial stimulus. The effects of pre- or postoperative intraperitoneal administration of morphine (2 to 8 mg/kg, dipyrone (40 and 80 mg/kg, diclofenac (2 to 8 mg/kg, ketoprofen (10 and 20 mg/kg, and tenoxicam (10 and 20 mg/kg were studied in a rat model of post-incisional pain. Groups of 5 to 8 male Wistar rats (140-160 g were used to test each drug dose. An incision was made on the plantar surface of a hind paw and the changes in the withdrawal threshold to mechanical stimulation were evaluated with Von Frey filaments at 1, 2, 6 and 24 h after the surgery. Tenoxicam was given 12 or 6 h preoperatively, whereas the remaining drugs were given 2 h or 30 min preoperatively. Postoperative drugs were all given 5 min after surgery. No drug abolished allodynia when injected before or after surgery, but thresholds were significantly higher than in control during up to 2 h following ketoprofen, 6 h following diclofenac, and 24 h following morphine, dipyrone or tenoxicam when drugs were injected postoperatively. Significant differences between pre- and postoperative treatments were obtained only with ketoprofen administered 30 min before surgery. Preoperative (2 h intraplantar, but not intrathecal, ketoprofen reduced the post-incisional pain for up to 24 h after surgery. It is concluded that stimuli generated in the inflamed tissue, rather than changes in the central nervous system are relevant for the persistence of pain in the model of post-incisional pain.

N-hexane neuropathy with vertigo and cold allodynia in a silk screen printer: A case study

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Sunil Pradhan

2015-10-01

Full Text Available N-hexane neuropathy is an occupational disease caused by exposure to n-hexane, which is used as a solvent in silk screen printing. Here, we describe a 35-year-old man, a silk screen printer by profession, who presented with dizziness, distal swelling of both lower limbs for 10 months and tingling and burning sensation in both feet for 9.5 months along with cold allodynia. The patient had normal results of a motor and sensory system examination, apart from an impaired temperature sense. Nerve conduction tests showed a conduction block in bilateral common peroneal nerves and absence of conduction in bilateral sural nerves. These symptoms resolved when further exposure to n-hexane was ceased but cold allodynia remained. Thus, cold allodynia and impaired temperature sense can be a manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction studies can be detected in n-hexane neuropathy patients, even before clinical examination detects any such abnormalities. In the case of the patients presenting with sensory motor neuropathy, history of occupational exposure to n-hexane becomes important, as the sooner the disease is detected, the better the chances of recovery.

Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

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Willing, Ryan; King, Graham J W; Johnson, James A

2015-11-26

Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (pengineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

DEFF Research Database (Denmark)

Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.

2006-01-01

affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically......Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result in a deficiency of the lysosomal enzyme α-galactosidase A causing accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. Given the X-linked inheritance, male patients are severely....... The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p...

N-hexane neuropathy with vertigo and cold allodynia in a silk screen printer: A case study.

Science.gov (United States)

Pradhan, Sunil; Tandon, Ruchika

2015-01-01

N-hexane neuropathy is an occupational disease caused by exposure to n-hexane, which is used as a solvent in silk screen printing. Here, we describe a 35-year-old man, a silk screen printer by profession, who presented with dizziness, distal swelling of both lower limbs for 10 months and tingling and burning sensation in both feet for 9.5 months along with cold allodynia. The patient had normal results of a motor and sensory system examination, apart from an impaired temperature sense. Nerve conduction tests showed a conduction block in bilateral common peroneal nerves and absence of conduction in bilateral sural nerves. These symptoms resolved when further exposure to n-hexane was ceased but cold allodynia remained. Thus, cold allodynia and impaired temperature sense can be a manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction studies can be detected in n-hexane neuropathy patients, even before clinical examination detects any such abnormalities. In the case of the patients presenting with sensory motor neuropathy, history of occupational exposure to n-hexane becomes important, as the sooner the disease is detected, the better the chances of recovery. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Nociceptin/orphanin FQ peptide receptor antagonist JTC-801 reverses pain and anxiety symptoms in a rat model of post-traumatic stress disorder

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Zhang, Y; Simpson-Durand, C D; Standifer, K M

2015-01-01

BACKGROUND AND PURPOSE Single-prolonged stress (SPS), a rat model of post-traumatic stress disorder (PTSD), also induces long-lasting hyperalgesia associated with hypocortisolism and elevated nociceptin/orphanin FQ (N/OFQ) levels in serum and CSF. Here, we determined the effect of JTC-801 (N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride), a nociceptin/orphanin FQ peptide (NOP) receptor antagonist, on symptoms of pain and anxiety in rats after SPS exposure, and examined N/OFQ-NOP receptor system changes. EXPERIMENTAL APPROACH Male Sprague Dawley rats received JTC-801 (6 mg kg−1 i.p., once daily) during days 7–21 of SPS. The ability of JTC-801 to inhibit N/OFQ-stimulated [35S]-GTPγS binding was confirmed in rat brain membranes. Anxiety-like behaviour and pain sensitivity were monitored by changes in elevated plus maze performance and withdrawal responses to thermal and mechanical stimuli. Serum corticosterone and N/OFQ content in CSF, serum and brain tissues were determined by radioimmunoassay; NOP receptor protein and gene expression in amygdala, hippocampus and periaqueductal grey (PAG) were examined by immunoblotting and real-time PCR respectively. KEY RESULTS JTC-801 treatment reversed SPS-induced mechanical allodynia, thermal hyperalgesia, anxiety-like behaviour and hypocortisolism. Elevated N/OFQ levels in serum, CSF, PAG and hippocampus at day 21 of SPS were blocked by JTC-801; daily JTC-801 treatment also reversed NOP receptor protein and mRNA up-regulation in amygdala and PAG. CONCLUSION AND IMPLICATIONS JTC-801 reversed SPS-induced anxiety- and pain-like behaviours, and NOP receptor system up-regulation. These findings suggest that N/OFQ plays an important role in hyperalgesia and allodynia maintenance after SPS. NOP receptor antagonists may provide effective treatment for co-morbid PTSD and pain. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view

Nociceptin/orphanin FQ peptide receptor antagonist JTC-801 reverses pain and anxiety symptoms in a rat model of post-traumatic stress disorder.

Science.gov (United States)

Zhang, Y; Simpson-Durand, C D; Standifer, K M

2015-01-01

Single-prolonged stress (SPS), a rat model of post-traumatic stress disorder (PTSD), also induces long-lasting hyperalgesia associated with hypocortisolism and elevated nociceptin/orphanin FQ (N/OFQ) levels in serum and CSF. Here, we determined the effect of JTC-801 (N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride), a nociceptin/orphanin FQ peptide (NOP) receptor antagonist, on symptoms of pain and anxiety in rats after SPS exposure, and examined N/OFQ-NOP receptor system changes. Male Sprague Dawley rats received JTC-801 (6 mg kg(-1) i.p., once daily) during days 7-21 of SPS. The ability of JTC-801 to inhibit N/OFQ-stimulated [(35) S]-GTPγS binding was confirmed in rat brain membranes. Anxiety-like behaviour and pain sensitivity were monitored by changes in elevated plus maze performance and withdrawal responses to thermal and mechanical stimuli. Serum corticosterone and N/OFQ content in CSF, serum and brain tissues were determined by radioimmunoassay; NOP receptor protein and gene expression in amygdala, hippocampus and periaqueductal grey (PAG) were examined by immunoblotting and real-time PCR respectively. JTC-801 treatment reversed SPS-induced mechanical allodynia, thermal hyperalgesia, anxiety-like behaviour and hypocortisolism. Elevated N/OFQ levels in serum, CSF, PAG and hippocampus at day 21 of SPS were blocked by JTC-801; daily JTC-801 treatment also reversed NOP receptor protein and mRNA up-regulation in amygdala and PAG. JTC-801 reversed SPS-induced anxiety- and pain-like behaviours, and NOP receptor system up-regulation. These findings suggest that N/OFQ plays an important role in hyperalgesia and allodynia maintenance after SPS. NOP receptor antagonists may provide effective treatment for co-morbid PTSD and pain. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014

The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

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Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

2009-10-08

Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

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Ombretta Caspani

Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

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Koh, Won Uk; Choi, Seong Soo; Lee, Jong Hyuk; Lee, So Hee; Lee, Sun Kyung; Lee, Yoon Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

2014-11-04

Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

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Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration?

DEFF Research Database (Denmark)

Sjøgren, P; Thunedborg, L P; Christrup, Lona Louring

1998-01-01

Recently, clinical reports have suggested a relationship between the occurrence of hyperalgesia, allodynia and/or myoclonus and treatment with high doses of morphine in humans. Although few clinical descriptions of these phenomena are available, experimental work supports the notion that high dos...

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

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Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. PMID:27746208

The criterion for time symmetry of probabilistic theories and the reversibility of quantum mechanics

International Nuclear Information System (INIS)

Holster, A T

2003-01-01

Physicists routinely claim that the fundamental laws of physics are 'time symmetric' or 'time reversal invariant' or 'reversible'. In particular, it is claimed that the theory of quantum mechanics is time symmetric. But it is shown in this paper that the orthodox analysis suffers from a fatal conceptual error, because the logical criterion for judging the time symmetry of probabilistic theories has been incorrectly formulated. The correct criterion requires symmetry between future-directed laws and past-directed laws. This criterion is formulated and proved in detail. The orthodox claim that quantum mechanics is reversible is re-evaluated. The property demonstrated in the orthodox analysis is shown to be quite distinct from time reversal invariance. The view of Satosi Watanabe that quantum mechanics is time asymmetric is verified, as well as his view that this feature does not merely show a de facto or 'contingent' asymmetry, as commonly supposed, but implies a genuine failure of time reversal invariance of the laws of quantum mechanics. The laws of quantum mechanics would be incompatible with a time-reversed version of our universe

Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

Science.gov (United States)

Shahid, M; Subhan, F; Ahmad, N; Ali, G; Akbar, S; Fawad, K; Sewell, R D E

2017-04-01

Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the

Different mechanisms to explain the reversed effects of mental health on work characteristics

NARCIS (Netherlands)

Lange, A.H. de; Taris, T.W.; Kompier, M.A.J.; Houtman, I.L.D.; Bongers, P.M.

2005-01-01

Objectives: The number of longitudinal studies reporting evidence for reversed effects of strain on work is growing, but evidence regarding the mechanisms underlying such effects is scarce. In this study, earlier longitudinal findings were reviewed, and the following four mechanisms for reversed

The analgesic effect of orexin-A in a murine model of chemotherapy-induced neuropathic pain.

Science.gov (United States)

Toyama, Satoshi; Shimoyama, Naohito; Shimoyama, Megumi

2017-02-01

Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN). Several chemotherapeutic agents used for the treatment of malignant diseases induce dose-limiting neuropathic pain that compromises patients' quality of life. Here, we examined the analgesic effect of orexin-A in a murine model of CIPN, and compared it with the effect of duloxetine, the only drug recommended for the treatment of CIPN pain in patients. CIPN was induced in male BALB/c mice by repeated intraperitoneal injection of oxaliplatin, a platinum chemotherapeutic agent used for the treatment of advanced colorectal cancer. Neuropathic mechanical allodynia was assessed by the von Frey test, and the effect on acute thermal pain was assessed by the tail flick test. Intracerebroventricularly administered orexin-A dose-dependently attenuated oxaliplatin-induced mechanical allodynia and increased tail flick latencies. Oxaliplatin-induced mechanical allodynia was completely reversed by orexin-A at a low dose that did not increase tail flick latency. Duloxetine only partially reversed mechanical allodynia and had no effect on tail flick latency. The analgesic effect of orexin-A on oxaliplatin-induced mechanical allodynia was completely antagonized by prior intraperitoneal injection of SB-408124 (orexin type-1 receptor antagonist), but not by prior intraperitoneal injection of TCS-OX2-29 (orexin type-2 receptor antagonist). Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is

The paleomagnetic field and possible mechanisms for the formation of reversed rock magnetization

International Nuclear Information System (INIS)

Trukhin, Vladimir I.; Bezaeva, Natalia; Kurochkina, Evgeniya

2006-01-01

Investigations of ancient magnetized rocks show that their natural remanent magnetization (NRM) can be oriented in the direction of modern geomagnetic field (GMF) as well as in the opposite direction. It is supposed that reversed NRM is related to reversals of the GMF in the past geological periods. During reversals, the strength of the GMF is near zero and can cause the destruction of living organisms as a result of powerful space and solar radiation, which, in the absence of the GMF, can reach the Earth's surface. That is why the question of reality of the GMF reversals is of global ecological importance. There is also another natural mechanism for the formation of reversed NRM-the self-reversal of magnetization as a result of thermomagnetization of rocks. In the paper, both natural processes for the formation of reversed NRM in rocks are discussed, and the results of experimental research on the physical mechanism of self-reversal of magnetization in continental and oceanic rocks are presented. The results of computer modeling of the self-reversal phenomenon are also presented

The paleomagnetic field and possible mechanisms for the formation of reversed rock magnetization

Energy Technology Data Exchange (ETDEWEB)

Trukhin, Vladimir I. [Faculty of Physics, Moscow State University, 119992 Moscow (Russian Federation)]. E-mail: trukhin@phys.msu.ru; Bezaeva, Natalia [Faculty of Physics, Moscow State University, 119992 Moscow (Russian Federation); Kurochkina, Evgeniya [Faculty of Physics, Moscow State University, 119992 Moscow (Russian Federation)

2006-05-15

Investigations of ancient magnetized rocks show that their natural remanent magnetization (NRM) can be oriented in the direction of modern geomagnetic field (GMF) as well as in the opposite direction. It is supposed that reversed NRM is related to reversals of the GMF in the past geological periods. During reversals, the strength of the GMF is near zero and can cause the destruction of living organisms as a result of powerful space and solar radiation, which, in the absence of the GMF, can reach the Earth's surface. That is why the question of reality of the GMF reversals is of global ecological importance. There is also another natural mechanism for the formation of reversed NRM-the self-reversal of magnetization as a result of thermomagnetization of rocks. In the paper, both natural processes for the formation of reversed NRM in rocks are discussed, and the results of experimental research on the physical mechanism of self-reversal of magnetization in continental and oceanic rocks are presented. The results of computer modeling of the self-reversal phenomenon are also presented.

Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain.

Science.gov (United States)

Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J

2013-01-01

Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

Mechanism design of reverse auction on concession period and generalized quality for PPP projects

Institute of Scientific and Technical Information of China (English)

Xianjia WANG; Shiwei WU

2017-01-01

Reverse auctions of PPP projects usually require the bid to specify several characteristics of quality and the concession period to be fulfilled.This paper sets up a summary function of generalized quality,which contributes to reducing the dimensions of information.Thus,the multidimensional reverse auction model of a PPP project can be replaced by a two-dimensional direct mechanism based on the concession period and the generalized quality.Based on the theory of the revelation principle,the feasibility conditions,equilibrium solution and generalized quality requirements of such a mechanism,considering the influence of a variable investment structure are described.Moreover,two feasible multidimensional reverse auctions for implementing such a direct mechanism:Adjusting the scoring function and establishing a special reverse auction rule are built.The analysis shows that in these types of reverse auctions,optimal allocation can be achieved,the social benefit under the incomplete information will be maximized,and the private sector with the highest integrated management level wins the bid.In such a direct mechanism,the investment and financial pressure of the public sector can be reduced.

Upregulation of calcium channel alpha-2-delta-1 subunit in dorsal horn contributes to spinal cord injury-induced tactile allodynia.

Science.gov (United States)

Kusuyama, Kazuki; Tachibana, Toshiya; Yamanaka, Hiroki; Okubo, Masamichi; Yoshiya, Shinichi; Noguchi, Koichi

2018-01-31

Spinal cord injury (SCI) commonly results not only in motor paralysis but also in the emergence of neuropathic pain (NeuP), both of which can impair the quality of life for patients with SCI. In the clinical field, it is well known that pregabalin, which binds to the voltage-gated calcium channel alpha-2-delta-1 (α 2 δ-1) subunit has therapeutic effects on NeuP after SCI. A previous study has demonstrated that SCI increased α 2 δ-1 in the L4-L6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase of α 2 δ-1 was correlated with tactile allodynia of the hind paw. However, the detailed feature of an increase in α 2 δ-1 protein in the spinal dorsal horn and the mechanism of pregabalin effect on SCI-induced NeuP have not been fully examined. This study aimed to examine the detailed distribution of α 2 δ-1 expression in the lumbar spinal cord after thoracic SCI in rats and the correlation of the therapeutic effect of pregabalin in SCI rats. Male Sprague-Dawley rats underwent thoracic (T10) spinal cord contusion injury using the IH impactor device. Spinal cord injury rats received pregabalin (30 mg/kg) once a day for 2 weeks over a 4-week period after SCI. The mechanical threshold in the rat hind paw was measured over 4 weeks. Alpha-2-delta-1 expression in the lumbar spinal cord and in the dorsal root ganglion (DRG) was analyzed using immunohistochemistry and in situ hybridization histochemistry. A significant reduction of the withdrawal threshold of mechanical stimuli to the hind paw was observed for 2 weeks and continued at least 4 weeks after SCI. In the control rats, expression of α 2 δ-1 immunoreactivity was detected mainly in laminae I and II in the lumbar dorsal horn. Thoracic SCI significantly increased α 2 δ-1 immunoreactivity in laminae I and II in the lumbar dorsal horn 4 weeks after SCI; however, thoracic SCI did not affect the expression of α 2 δ-1 mRNA in the L4 and L5 DRGs. Meanwhile, the signal intensity of α 2 �

Virtual visual reminiscing pain stimulation of allodynia patients activates cortical representation of pain and emotions. fMRI study

International Nuclear Information System (INIS)

Ikemoto, Tatsunori; Ushida, Takahiro; Taniguchi, Shinichirou; Tania, Toshikazu; Zinchuk, V.; Morio, Kazuo; Sasaki, Toshikazu

2004-01-01

It is widely known that sensation of the pain is derived from sensory-discriminative factor and emotional factor. Especially in chronic pain, emotional factors and psychosocial backgrounds are more likely to contribute for the patients' discomfort. The aim of this study is to investigate how emotional factor of pain participates in intractable pain. We employed functional MRI (fMRI) to compare the brain activations occurring in the orthopaedic neuropathic pain patients with allodynia and normal individuals in response to the visual virtual painful experience. During fMRI scanning, a video demonstrating an actual tactile stimulation of the palm and its imitation were shown to participants. In contrast to normal individuals, allodynia patients also displayed activation of the areas reflecting emotions: frontal lobe and anterior cingulate. These findings suggest that brain have important role in the development and maintaining of peripheral originated chronic painful condition. (author)

Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

Science.gov (United States)

Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

2015-12-01

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

Reversible Guest Exchange Mechanisms in Supramolecular Host-GuestAssemblies

Energy Technology Data Exchange (ETDEWEB)

Pluth, Michael D.; Raymond, Kenneth N.

2006-09-01

Synthetic chemists have provided a wide array of supramolecular assemblies able to encapsulate guest molecules. The scope of this tutorial review focuses on supramolecular host molecules capable of reversibly encapsulating polyatomic guests. Much work has been done to determine the mechanism of guest encapsulation and guest release. This review covers common methods of monitoring and characterizing guest exchange such as NMR, UV-VIS, mass spectroscopy, electrochemistry, and calorimetry and also presents representative examples of guest exchange mechanisms. The guest exchange mechanisms of hemicarcerands, cucurbiturils, hydrogen-bonded assemblies, and metal-ligand assemblies are discussed. Special attention is given to systems which exhibit constrictive binding, a motif common in supramolecular guest exchange systems.

Enhancement of mechanical properties of a TRIP-aided austenitic stainless steel by controlled reversion annealing

Energy Technology Data Exchange (ETDEWEB)

Hamada, A.S., E-mail: atef.hamada@suezuniv.edu.eg [Centre for Advanced Steels Research, Box 4200, University of Oulu, 90014 Oulu (Finland); Metallurgical and Materials Engineering Department, Faculty of Petroleum & Mining Engineering, Suez University, Box 43721, Suez (Egypt); Kisko, A.P. [Centre for Advanced Steels Research, Box 4200, University of Oulu, 90014 Oulu (Finland); Sahu, P. [Department of Physics, Jadavpur University, Kolkata 700032 (India); Karjalainen, L.P. [Centre for Advanced Steels Research, Box 4200, University of Oulu, 90014 Oulu (Finland)

2015-03-25

Controlled martensitic reversion annealing was applied to a heavily cold-worked metastable austenitic low-Ni Cr–Mn austenitic stainless steel (Type 201) to obtain different ultrafine austenite grain sizes to enhance the mechanical properties, which were then compared with the conventional coarse-grained steel. Characterization of the deformed and reversion annealed microstructures was performed by electron back scattered diffraction (EBSD), X-ray diffraction (XRD) and light and transmission electron microscopy (TEM). The steel with a reverted grain size ~1.5 μm due to annealing at 800 °C for 10 s showed significant improvements in the mechanical properties with yield stress ~800 MPa and tensile strength ~1100 MPa, while the corresponding properties of its coarse grained counterpart were ~450 MPa and ~900 MPa, respectively. However, the fracture elongation of the reversion annealed steel was ~50% as compared to ~70% in the coarse grained steel. A further advantage is that the anisotropy of mechanical properties present in work-hardened steels also disappears during reversion annealing.

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

Directory of Open Access Journals (Sweden)

Nikele Nadur-Andrade

2016-10-01

Full Text Available Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv, as well as the mechanisms involved was investigated.Bmv (1 μg was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

Directory of Open Access Journals (Sweden)

Li Li

2014-01-01

Full Text Available The present study examined nociceptive behaviors and the expression of phosphorylated cAMP response element-binding protein (pCREB in the dorsal horn of the lumbar spinal cord and the dorsal root ganglion (DRG evoked by bee venom (BV. The effect of intraplantar preapplication of the somatostatin analog octreotide on nociceptive behaviors and pCREB expression was also examined. Subcutaneous injection of BV into the rat unilateral hindpaw pad induced significant spontaneous nociceptive behaviors, primary mechanical allodynia, primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide pretreatment significantly attenuated the BV-induced lifting/licking response and mechanical allodynia. Local injection of octreotide also significantly reduced pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore, pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed the octreotide-induced inhibition of the lifting/licking response, mechanical allodynia, and the expression of pCREB. These results suggest that BV can induce nociceptive responses and somatostatin receptors are involved in mediating the antinociception, which provides new evidence for peripheral analgesic action of somatostatin in an inflammatory pain state.

How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

Science.gov (United States)

Truini, Andrea; Cruccu, Giorgio

2016-02-01

Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

Reverse mechanical after effect during hydrogenation of zone refined iron

Energy Technology Data Exchange (ETDEWEB)

Spivak, L.V.; Skryabina, N.E.; Kurmaeva, L.D.; Smirnov, L.V. (Permskij Gosudarstvennyj Univ. (USSR); AN SSSR, Sverdlovsk. Inst. Fiziki Metallov)

1984-12-01

The relationship between the process of hydrogenation and the reverse mechanical after effect (RMA) microplastic deformation in the zone refined iron has been studied. Metallographic investigations and mechanical testing of the samples hydrogenated under torsional strain have been performed. It is shown that in the zone refined iron the formation of voids responsible for irreversible hydrogen embrittlement does not occur, but the hydrogen-initiated RMA strain is conserved, i. e. the RMA effects are independent of the presence of discontinuities.

The effect of temperature on the magnetization reversal mechanism in sintered PrFeB

International Nuclear Information System (INIS)

Crew, D. C.; Lewis, L. H.; Welch, D. O.; Pourarian, F.

2000-01-01

To understand the effects of nucleation fields and intergranular dipolar interactions on the magnetization reversal mechanism, recoil curves from the major hysteresis loop have been measured on a sample of sintered PrFeB as a function of temperature from 150 to 300 K. At room temperature the reversible magnetization behavior indicates a reversal mechanism of nucleation of domain walls whose motion after nucleation is resisted by dipolar fields. As the temperature is reduced, the coercivity, and hence the nucleation field, is observed to increase while the dipolar fields, dependent on microstructure and saturation magnetization, remain approximately constant. These temperature-dependent changes in the relative magnitudes of the dipolar field and nucleation field cause the reversible magnetization behavior to change from domain wall motion to rotation. This change in behavior is attributed to the supposition that at temperatures where the nucleation field exceeds the dipolar field, once nucleated, domain walls are swept out of the material. (c) 2000 American Institute of Physics

Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

Science.gov (United States)

Peng, Zhang

2018-03-01

the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

Synthetically chemical-electrical mechanism for controlling large scale reversible deformation of liquid metal objects

Science.gov (United States)

Zhang, Jie; Sheng, Lei; Liu, Jing

2014-11-01

Reversible deformation of a machine holds enormous promise across many scientific areas ranging from mechanical engineering to applied physics. So far, such capabilities are still hard to achieve through conventional rigid materials or depending mainly on elastomeric materials, which however own rather limited performances and require complicated manipulations. Here, we show a basic strategy which is fundamentally different from the existing ones to realize large scale reversible deformation through controlling the working materials via the synthetically chemical-electrical mechanism (SCHEME). Such activity incorporates an object of liquid metal gallium whose surface area could spread up to five times of its original size and vice versa under low energy consumption. Particularly, the alterable surface tension based on combination of chemical dissolution and electrochemical oxidation is ascribed to the reversible shape transformation, which works much more flexible than many former deformation principles through converting electrical energy into mechanical movement. A series of very unusual phenomena regarding the reversible configurational shifts are disclosed with dominant factors clarified. This study opens a generalized way to combine the liquid metal serving as shape-variable element with the SCHEME to compose functional soft machines, which implies huge potential for developing future smart robots to fulfill various complicated tasks.

Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

Directory of Open Access Journals (Sweden)

Ma Fei

2012-12-01

Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

Nano/ultrafine grained austenitic stainless steel through the formation and reversion of deformation-induced martensite: Mechanisms, microstructures, mechanical properties, and TRIP effect

Energy Technology Data Exchange (ETDEWEB)

Shirdel, M., E-mail: mshirdel1989@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Mirzadeh, H., E-mail: hmirzadeh@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Parsa, M.H., E-mail: mhparsa@ut.ac.ir [School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, P.O. Box 11155-4563, Tehran (Iran, Islamic Republic of); Center of Excellence for High Performance Materials, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of); Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran (Iran, Islamic Republic of)

2015-05-15

A comprehensive study was carried out on the strain-induced martensitic transformation, its reversion to austenite, the resultant grain refinement, and the enhancement of strength and strain-hardening ability through the transformation-induced plasticity (TRIP) effect in a commercial austenitic 304L stainless steel with emphasis on the mechanisms and the microstructural evolution. A straightforward magnetic measurement device, which is based on the measurement of the saturation magnetization, for evaluating the amount of strain-induced martensite after cold rolling and reversion annealing in metastable austenitic stainless steels was used, which its results were in good consistency with those of the X-ray diffraction (XRD) method. A new parameter called the effective reduction in thickness was introduced, which corresponds to the reasonable upper bound on the obtainable martensite fraction based on the saturation in the martensitic transformation. By means of thermodynamics calculations, the reversion mechanisms were estimated and subsequently validated by experimental results. The signs of thermal martensitic transformation at cooling stage after reversion at 850 °C were found, which was attributed to the rise in the martensite start temperature due to the carbide precipitation. After the reversion treatment, the average grain sizes were around 500 nm and the nanometric grains of the size of ~ 65 nm were also detected. The intense grain refinement led to the enhanced mechanical properties and observation of the change in the work-hardening capacity and TRIP effect behavior. A practical map as a guidance for grain refining and characterizing the stability against grain growth was proposed, which shows the limitation of the reversion mechanism for refinement of grain size. - Graphical abstract: Display Omitted - Highlights: • Nano/ultrafine grained austenitic stainless steel through martensite treatment • A parameter descriptive of a reasonable upper bound on

Nano/ultrafine grained austenitic stainless steel through the formation and reversion of deformation-induced martensite: Mechanisms, microstructures, mechanical properties, and TRIP effect

International Nuclear Information System (INIS)

Shirdel, M.; Mirzadeh, H.; Parsa, M.H.

2015-01-01

A comprehensive study was carried out on the strain-induced martensitic transformation, its reversion to austenite, the resultant grain refinement, and the enhancement of strength and strain-hardening ability through the transformation-induced plasticity (TRIP) effect in a commercial austenitic 304L stainless steel with emphasis on the mechanisms and the microstructural evolution. A straightforward magnetic measurement device, which is based on the measurement of the saturation magnetization, for evaluating the amount of strain-induced martensite after cold rolling and reversion annealing in metastable austenitic stainless steels was used, which its results were in good consistency with those of the X-ray diffraction (XRD) method. A new parameter called the effective reduction in thickness was introduced, which corresponds to the reasonable upper bound on the obtainable martensite fraction based on the saturation in the martensitic transformation. By means of thermodynamics calculations, the reversion mechanisms were estimated and subsequently validated by experimental results. The signs of thermal martensitic transformation at cooling stage after reversion at 850 °C were found, which was attributed to the rise in the martensite start temperature due to the carbide precipitation. After the reversion treatment, the average grain sizes were around 500 nm and the nanometric grains of the size of ~ 65 nm were also detected. The intense grain refinement led to the enhanced mechanical properties and observation of the change in the work-hardening capacity and TRIP effect behavior. A practical map as a guidance for grain refining and characterizing the stability against grain growth was proposed, which shows the limitation of the reversion mechanism for refinement of grain size. - Graphical abstract: Display Omitted - Highlights: • Nano/ultrafine grained austenitic stainless steel through martensite treatment • A parameter descriptive of a reasonable upper bound on

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

Science.gov (United States)

Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Thickness dependence of magnetization reversal mechanism in perpendicularly magnetized L1{sub 0} FePt films

Energy Technology Data Exchange (ETDEWEB)

Bi, Mei; Wang, Xin, E-mail: xinwang@uestc.edu.cn; Lu, Haipeng; Zhang, Li; Deng, Longjiang; Xie, Jianliang

2017-04-15

We have studied the magnetic switching behavior of L1{sub 0}-ordered FePt films with varying thickness. It was found that coercivity is strongly dependent on the film thickness. The obvious variations of the coercivity in the thin films are confirmed by the measurements of structural and magnetic properties. With increasing thickness, the degree of L1{sub 0} chemical ordering increased, while the magnetization reversal process transforms from a pinned two-steps magnetization reversal to a comparatively smooth domain wall motion behavior. Although considering anisotropy, exchange interaction and applied magnetic field, the switching behavior in films is quite complex, the main features of the magnetization reversal mechanism can be understood by performing detailed investigation on the effect of the deposition temperature and the angle of magnetic field. - Highlights: • Series of FePt films with L1{sub 0} phase have been prepared. • We focused on the magnetization reversal mechanism with varying thicknesses. • The angle-dependence of switching process is revealed in the FePt films. • Different switching mechanisms were found by increasing the film thickness.

Neural mechanisms underlying sensitivity to reverse-phi motion in the fly.

Science.gov (United States)

Leonhardt, Aljoscha; Meier, Matthias; Serbe, Etienne; Eichner, Hubert; Borst, Alexander

2017-01-01

Optical illusions provide powerful tools for mapping the algorithms and circuits that underlie visual processing, revealing structure through atypical function. Of particular note in the study of motion detection has been the reverse-phi illusion. When contrast reversals accompany discrete movement, detected direction tends to invert. This occurs across a wide range of organisms, spanning humans and invertebrates. Here, we map an algorithmic account of the phenomenon onto neural circuitry in the fruit fly Drosophila melanogaster. Through targeted silencing experiments in tethered walking flies as well as electrophysiology and calcium imaging, we demonstrate that ON- or OFF-selective local motion detector cells T4 and T5 are sensitive to certain interactions between ON and OFF. A biologically plausible detector model accounts for subtle features of this particular form of illusory motion reversal, like the re-inversion of turning responses occurring at extreme stimulus velocities. In light of comparable circuit architecture in the mammalian retina, we suggest that similar mechanisms may apply even to human psychophysics.

Reverse Transcriptase Mechanism of Somatic Hypermutation: 60 Years of Clonal Selection Theory

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Edward J. Steele

2017-11-01

Full Text Available The evidence for the reverse transcriptase mechanism of somatic hypermutation is substantial and multifactorial. In this 60th anniversary year of the publication of Sir MacFarlane Burnet’s Clonal Selection Theory, the evidence is briefly reviewed and updated.

Asymmetric effect of mechanical stress on the forward and reverse reaction catalyzed by an enzyme.

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Collin Joseph

Full Text Available The concept of modulating enzymatic activity by exerting a mechanical stress on the enzyme has been established in previous work. Mechanical perturbation is also a tool for probing conformational motion accompanying the enzymatic cycle. Here we report measurements of the forward and reverse kinetics of the enzyme Guanylate Kinase from yeast (Saccharomyces cerevisiae. The enzyme is held in a state of stress using the DNA spring method. The observation that mechanical stress has different effects on the forward and reverse reaction kinetics suggests that forward and reverse reactions follow different paths, on average, in the enzyme's conformational space. Comparing the kinetics of the stressed and unstressed enzyme we also show that the maximum speed of the enzyme is comparable to the predictions of the relaxation model of enzyme action, where we use the independently determined dissipation coefficient [Formula: see text] for the enzyme's conformational motion. The present experiments provide a mean to explore enzyme kinetics beyond the static energy landscape picture of transition state theory.

Bis(phenylimidazoselenazolyl) diselenide elicits antinociceptive effect by modulating myeloperoxidase activity, NOx and NFkB levels in the collagen-induced arthritis mouse model.

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Chagas, Pietro M; Fulco, Bruna C W; Sari, Marcel H M; Roehrs, Juliano A; Nogueira, Cristina W

2017-08-01

Bis(phenylimidazoselenazolyl) diselenide (BPIS) is an organoselenium with acute antinociceptive and antioxidant properties. The aim of this study was to investigate BPIS effect on a collagen-induced arthritis (CIA) model in mice. Protocol of exposure consisted in arthritis induction by chicken collagen type II on day 0 with booster injection on day 21. On day 60 after collagen injection, incidence of mechanic allodynia (Von Frey test) or thermal hyperalgesia (hot plate test) was evaluated. During following 5 days, mice were treated with BPIS (0.1-1 mg/kg; p.o.; daily) or vehicle. On day 65, mice were killed, and paws and spinal cord were removed for analyses. Mice submitted to CIA model developed both mechanical allodynia and thermal hyperalgesia, which were reversed by BPIS at the highest dose. In paw, BPIS reversed the increase in myeloperoxidase activity in the CIA group. In the spinal cord, BPIS decreased NOx and NFkB levels increased in the CIA group. BPIS-treated animals had lower cyclooxygenase-2 levels in the spinal cord. The myeloperoxidase activity in paw and NOx and NFkB levels in spinal cord are related to antinociceptive properties of BPIS in CIA model. © 2017 Royal Pharmaceutical Society.

In Situ Transmission Electron Microscopy Studies of the Magnetization Reversal Mechanism in Information Storage Materials.

Science.gov (United States)

Petford-Long; Portier; Bayle-Guillemaud; Anthony; Brug

1998-05-01

: The Foucault and Fresnel modes of Lorentz microscopy, together with a quantitative magnetization mapping technique, summed image differential phase-contrast imaging, were used to study the magnetization reversal mechanism of the sense layer in spin-valve structures exhibiting the giant magnetoresistance effect. In addition to studies of sheet film, lithographically defined spin-valve elements were investigated. A current can be passed through the element during magnetizing so that the effect of the applied current on the giant magnetoresistance and magnetization reversal mechanism can be studied. Results are presented for a number of different spin-valve structures.

Neural mechanisms underlying sensitivity to reverse-phi motion in the fly

Science.gov (United States)

Meier, Matthias; Serbe, Etienne; Eichner, Hubert; Borst, Alexander

2017-01-01

Optical illusions provide powerful tools for mapping the algorithms and circuits that underlie visual processing, revealing structure through atypical function. Of particular note in the study of motion detection has been the reverse-phi illusion. When contrast reversals accompany discrete movement, detected direction tends to invert. This occurs across a wide range of organisms, spanning humans and invertebrates. Here, we map an algorithmic account of the phenomenon onto neural circuitry in the fruit fly Drosophila melanogaster. Through targeted silencing experiments in tethered walking flies as well as electrophysiology and calcium imaging, we demonstrate that ON- or OFF-selective local motion detector cells T4 and T5 are sensitive to certain interactions between ON and OFF. A biologically plausible detector model accounts for subtle features of this particular form of illusory motion reversal, like the re-inversion of turning responses occurring at extreme stimulus velocities. In light of comparable circuit architecture in the mammalian retina, we suggest that similar mechanisms may apply even to human psychophysics. PMID:29261684

Water Diffusion Mechanism in Carbon Nanotube and Polyamide Nanocomposite Reverse Osmosis Membranes: A Possible Percolation-Hopping Mechanism

Science.gov (United States)

Araki, Takumi; Cruz-Silva, Rodolfo; Tejima, Syogo; Ortiz-Medina, Josue; Morelos-Gomez, Aaron; Takeuchi, Kenji; Hayashi, Takuya; Terrones, Mauricio; Endo, Morinobu

2018-02-01

This paper is a contribution to the Physical Review Applied collection in memory of Mildred S. Dresselhaus. The mechanism of water diffusion across reverse osmosis nanocomposite membranes made of carbon nanotubes (CNTs) and aromatic polyamide is not completely understood despite its high potential for desalination applications. While most of the groups have proposed that superflow inside the CNT might positively impact the water flow across membranes, here we show theoretical evidence that this is not likely the case in composite membranes because CNTs are usually oriented parallel to the membrane surface, not to mention that sometimes the nanotube cores are occluded. Instead, we propose an oriented diffusion mechanism that explains the high water permeation by decreasing the diffusion path of water molecules across the membranes, even in the presence of CNTs that behave as impermeable objects. Finally, we provide a comprehensive description of the molecular dynamics occurring in water desalination membranes by considering the bond polarizability caused by dynamic charge transfer and explore the use of molecular-dynamics-derived stochastic diffusion simulations. The proposed water diffusion mechanism offers an alternative and most likely explanation for the high permeation phenomena observed in CNTs and PA nanocomposite membranes, and its understanding can be helpful to design the next generation of reverse osmosis desalination membranes.

Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

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Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

2017-08-01

Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in

Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: A quantitative proteomics approach.

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Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

2016-04-14

Marine bioadhesives have unmatched performances in wet environments, being an inspiration for biomedical applications. In sea urchins specialized adhesive organs, tube feet, mediate reversible adhesion, being composed by a disc, producing adhesive and de-adhesive secretions, and a motile stem. After tube foot detachment, the secreted adhesive remains bound to the substratum as a footprint. Sea urchin adhesive is composed by proteins and sugars, but so far only one protein, Nectin, was shown to be over-expressed as a transcript in tube feet discs, suggesting its involvement in sea urchin adhesion. Here we use high-resolution quantitative mass-spectrometry to perform the first study combining the analysis of the differential proteome of an adhesive organ, with the proteome of its secreted adhesive. This strategy allowed us to identify 163 highly over-expressed disc proteins, specifically involved in sea urchin reversible adhesion; to find that 70% of the secreted adhesive components fall within five protein groups, involved in exocytosis and microbial protection; and to provide evidences that Nectin is not only highly expressed in tube feet discs but is an actual component of the adhesive. These results give an unprecedented insight into the molecular mechanisms underlying sea urchin adhesion, and opening new doors to develop wet-reliable, reversible, and ecological biomimetic adhesives. Sea urchins attach strongly but in a reversible manner to substratum, being a valuable source of inspiration for industrial and biomedical applications. Yet, the molecular mechanisms governing reversible adhesion are still poorly studied delaying the engineering of biomimetic adhesives. We used the latest mass spectrometry techniques to analyze the differential proteome of an adhesive organ and the proteome of its secreted adhesive, allowing us to uncover the key players in sea urchin reversible adhesion. We demonstrate, that Nectin, a protein previously pointed out as potentially

Geomagnetic polarity reversals as a mechanism for the punctuated equilibrium model of biological evolution

International Nuclear Information System (INIS)

Welsh, J.S.; Welsh, A.L.; Welsh, W.F.

2003-01-01

In contrast to what is predicted by classical Darwinian theory (phyletic gradualism), the fossil record typically displays a pattern of relatively sudden, dramatic changes as detailed by Eldregde and Gould's model of punctuated equilibrium. Evolutionary biologists have been at a loss to explain the ultimate source of the new mutations that drive evolution. One hypothesis holds that the abrupt speciation seen in the punctuated equilibrium model is secondary to an increased mutation rate resulting from periodically increased levels of ionizing radiation on the Earth's surface. Sporadic geomagnetic pole reversals, occurring every few million years on the average, are accompanied by alterations in the strength of the Earth's magnetic field and magnetosphere. This diminution may allow charged cosmic radiation to bombard Earth with less attenuation, thereby resulting in increased mutation rates. This episodic fluctuation in the magnetosphere is an attractive mechanism for the observed fossil record. Selected periods and epochs of geologic history for which data was available were reviewed for both geomagnetic pole reversal history and fossil record. Anomalies in either were scrutinized in greater depth and correlations were made. A 35 million year span (118-83 Ma) was identified during the Early/Middle Cretaceous period that was devoid of geomagnetic polarity reversals(the Cretaceous normal superchron). Examination of the fossil record (including several invertebrate and vertebrate taxons) during the Cretaceous normal superchron does not reveal any significant gap or slowing of speciation. Although increased terrestrial radiation exposure due to a diminution of the Earth's magnetosphere caused by a reversal of geomagnetic polarity is an attractive explanation for the mechanism of punctuated equilibrium, our investigation suggests that such polarity reversals cannot fully provide the driving force behind biological evolution. Further research is required to determine if

A Dynamic Pricing Reverse Auction-Based Resource Allocation Mechanism in Cloud Workflow Systems

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Xuejun Li

2016-01-01

Full Text Available Market-oriented reverse auction is an efficient and cost-effective method for resource allocation in cloud workflow systems since it can dynamically allocate resources depending on the supply-demand relationship of the cloud market. However, during the auction the price of cloud resource is usually fixed, and the current resource allocation mechanisms cannot adapt to the changeable market properly which results in the low efficiency of resource utilization. To address such a problem, a dynamic pricing reverse auction-based resource allocation mechanism is proposed. During the auction, resource providers can change prices according to the trading situation so that our novel mechanism can increase the chances of making a deal and improve efficiency of resource utilization. In addition, resource providers can improve their competitiveness in the market by lowering prices, and thus users can obtain cheaper resources in shorter time which would decrease monetary cost and completion time for workflow execution. Experiments with different situations and problem sizes are conducted for dynamic pricing-based allocation mechanism (DPAM on resource utilization and the measurement of Time⁎Cost (TC. The results show that our DPAM can outperform its representative in resource utilization, monetary cost, and completion time and also obtain the optimal price reduction rates.

A behavioral and pharmacological validation of the acetone spray test in gerbils with a chronic constriction injury.

NARCIS (Netherlands)

Vissers, K.C.P.; Meert, T.F.

2005-01-01

Cold and mechanical allodynia are important symptoms in patients with neuropathic pain. The study of cold allodynia in animals can help us to understand the underlying pathophysiological mechanisms of neuropathic pain and to validate drugs. The evaluation of cold allodynia in gerbils with a chronic

Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

Science.gov (United States)

Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

2015-12-01

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

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Jimcy Platholi

Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

Floral reversion mechanism in longan (Dimocarpus longan Lour.) revealed by proteomic and anatomic analyses.

Science.gov (United States)

You, Xiangrong; Wang, Lingxia; Liang, Wenyu; Gai, Yonghong; Wang, Xiaoyan; Chen, Wei

2012-02-02

Two-dimensional gel electrophoresis (2-DE) was used to analyze the proteins related to floral reversion in Dimocarpus longan Lour. Proteins were extracted from buds undergoing the normal process of flowering and from those undergoing floral reversion in three developing stages in D. longan. Differentially expressed proteins were identified from the gels after 2-DE analysis, which were confirmed using matrix-assisted laser desorption/ionization-time of flying-mass spectroscopy and protein database search. A total of 39 proteins, including 18 up-regulated and 21 down-regulated proteins, were classified into different categories, such as energy and substance metabolism, protein translation, secondary metabolism, phytohormone, cytoskeleton structure, regulation, and stress tolerance. Among these, the largest functional class was associated with primary metabolism. Down-regulated proteins were involved in photosynthesis, transcription, and translation, whereas up-regulated proteins were involved in respiration. Decreased flavonoid synthesis and up-regulated GA20ox might be involved in the floral reversion process. Up-regulated 14-3-3 proteins played a role in the regulation of floral reversion in D. longan by responding to abiotic stress. Observations via transmission electron microscopy revealed the ultrastructure changes in shedding buds undergoing floral reversion. Overall, the results provided insights into the molecular basis for the floral reversion mechanism in D. longan. Copyright © 2011 Elsevier B.V. All rights reserved.

Proteomic Identification of an Upregulated Isoform of Annexin A3 in the Spinal Cords of Rats in a Neuropathic Pain Model

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Wangyuan Zou

2017-09-01

Full Text Available Neuropathic pain (NP is induced by nerve damage or a disturbance in the peripheral or central nervous systems. Nerve damage causes the activation of sensitizing mechanisms in the peripheral and central nervous systems, which induces transcriptional and post-transcriptional alterations in sensory nerves. However, the underlying mechanisms of NP remain elusive. In the study, Two-dimensional gel electrophoresis (2DGE-based comparative proteomics identified 38 differential gel spots, and 15 differentially expressed proteins (DEPs between the sham and the chronic constriction injury (CCI-induced neuropathic pain rats. Of them, Annexin A3 (ANXA3 was significantly increased after CCI with Western blot analysis and immunofluorescence imaging. A lentivirus delivering ANXA3 shRNA (LV-shANXA3 was administered intrathecally to determine the analgesic effects of ANXA3 on allodynia and hyperalgesia in a CCI-induced neuropathic pain model in rats. Further study showed that LV-shANXA3 reversed the upregulation of ANXA3, alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. The study indicated that ANXA3 may play an important role in neuropathic pain.

Biophysical Insights into the Inhibitory Mechanism of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

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Nicolas Sluis-Cremer

2013-11-01

Full Text Available HIV-1 reverse transcriptase (RT plays a central role in HIV infection. Current United States Federal Drug Administration (USFDA-approved antiretroviral therapies can include one of five approved non-nucleoside RT inhibitors (NNRTIs, which are potent inhibitors of RT activity. Despite their crucial clinical role in treating and preventing HIV-1 infection, their mechanism of action remains elusive. In this review, we introduce RT and highlight major advances from experimental and computational biophysical experiments toward an understanding of RT function and the inhibitory mechanism(s of NNRTIs.

Quantum control of a chiral molecular motor driven by femtosecond laser pulses: Mechanisms of regular and reverse rotations

International Nuclear Information System (INIS)

Yamaki, M.; Hoki, K.; Kono, H.; Fujimura, Y.

2008-01-01

Rotational mechanisms of a chiral molecular motor driven by femtosecond laser pulses were investigated on the basis of results of a quantum control simulation. A chiral molecule, (R)-2-methyl-cyclopenta-2,4-dienecarboaldehyde, was treated as a molecular motor within a one-dimensional model. It was assumed that the motor is fixed on a surface and driven in the low temperature limit. Electric fields of femtosecond laser pulses driving both regular rotation of the molecular motor with a plus angular momentum and reverse rotation with a minus one were designed by using a global control method. The mechanism of the regular rotation is similar to that obtained by a conventional pump-dump pulse method: the direction of rotation is the same as that of the initial wave packet propagation on the potential surface of the first singlet (nπ*) excited state S 1 . A new control mechanism has been proposed for the reverse rotation that cannot be driven by a simple pump-dump pulse method. In this mechanism, a coherent Stokes pulse creates a wave packet localized on the ground state potential surface in the right hand side. The wave packet has a negative angular momentum to drive reverse rotation at an early time

A Review of Neuropathic Pain: From Diagnostic Tests to Mechanisms

OpenAIRE

Truini, Andrea

2017-01-01

Neuropathic pain develops when the somatosensory nervous system is affected by a lesion or disease. Diagnostic tests aimed at assessing somatosensory afferent pathway damage are therefore useful for diagnosing neuropathic pain. Neuropathic pain manifests with a range of different symptoms such as ongoing burning pain, squeezing or pressure pain, paroxysmal electric shock-like sensations, stabbing pain, or mechanical dynamic allodynia. The various types of neuropathic pain are associated with ...

Mechanism of flow reversal during solidification of an anomalous liquid

Science.gov (United States)

Kumar, Virkeshwar; Kumawat, Mitesh; Srivastava, Atul; Karagadde, Shyamprasad

2017-12-01

In a wide variety of fluidic systems involving thermal and compositional gradients, local density changes lead to the onset of natural convection that influences the process itself, for example, during phase-change phenomena and magmatic flows. Accurate knowledge of the flow characteristics is essential to quantify the impact of the flow of the processes. In this work, the first-ever demonstration of flow reversal during bottom-up solidification of water using full-field thermal and flow measurements and its direct impact on the solidifying interface is presented. Based on prior optical interferometric measurements of full-field temperature distribution in water during solidification, we use the particle image velocimetry technique to quantify and reveal the changing natural convection pattern arising solely due to the density anomaly of water between 0 °C and 4 °C. The independently captured thermal and flow fields show striking similarities and clearly elucidate the plausible mechanism explaining the formation of a curved interface at the stagnation point and the subsequent reversal of flow direction due to a changed interface morphology. A control volume analysis is further presented to estimate the energy invested in the formation of a perturbation and the resulting flip in the flow direction caused by this perturbation.

Analysis of reverse gate leakage mechanism of AlGaN/GaN HEMTs with N2 plasma surface treatment

Science.gov (United States)

Liu, Hui; Zhang, Zongjing; Luo, Weijun

2018-06-01

The mechanism of reverse gate leakage current of AlGaN/GaN HEMTs with two different surface treatment methods are studied by using C-V, temperature dependent I-V and theoretical analysis. At the lower reverse bias region (VR >- 3.5 V), the dominant leakage current mechanism of the device with N2 plasma surface treatment is the Poole-Frenkel emission current (PF), and Trap-Assisted Tunneling current (TAT) is the principal leakage current of the device which treated by HCl:H2O solution. At the higher reverse bias region (VR current of the device with N2 plasma surface treatment is one order of magnitude smaller than the device which treated by HCl:H2O solution. This is due to the recovery of Ga-N bond in N2 plasma surface treatment together with the reduction of the shallow traps in post-gate annealing (PGA) process. The measured results agree well with the theoretical calculations and demonstrate N2 plasma surface treatment can reduce the reverse leakage current of the AlGaN/GaN HEMTs.

The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer.

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Shanshan Wang

Full Text Available Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR. To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (--Epigallocatechin gallate (EGCG and Tetramethylpyrazine (TMP to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM-resistant Pumc-91 cells (Pumc-91/ADM were assessed by Cell Counting Kit-8 (CCK-8 cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR, immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer

Phytotherapeutic activity of curcumol: Isolation, GC-MS identification, and assessing potentials against acute and subchronic hyperglycemia, tactile allodynia, and hyperalgesia.

Science.gov (United States)

Raafat, Karim M; Omar, Amal G

2016-08-01

Curcumol has recently attracted special attention due to its potential activities in many chronic disorders. Moreover, the traditional role of turmeric [Curcuma longa L. (Zingiberaceae)] in suppression of hyperglycemia is of great interest. The present work explores the potential acute and subchronic antihyperglycemic, antinociceptive, and in vivo antioxidant effects of curcumol in alloxan-diabetic mice. Bio-guided fractionation, column-chromatography, and GC-MS were utilized to identify the most active compound of turmeric (curcumol). Turmeric (25, 50, and 100 mg/kg), the curcumol rich fraction (CRF) (7 mg/kg), and curcumol (20, 30, and 40 mg/kg) were assessed for their acute (6 h) and subchronic (8 d) antihyperglycemic potentials and antinociceptive effects (8 weeks) were measured, using hot-plate and tail-flick latencies and von-Frey filaments method and in vivo antioxidant effects in alloxan-diabetic mice. The most-active turmeric fraction was found to be rich in curcumol (45.5%) using GC-MS analysis method. The results proved that the highest dose levels of turmeric extract and curcumol exerted remarkable hypoglycemic activity with 41.4 and 39.3% drop in the mice glucose levels after 6 h, respectively. Curcumol (40 mg/kg) was found to be 9.4% more potent than turmeric extract (100 mg/kg) in subchronic management of diabetes. Curcumol also showed a significant improvement of peripheral nerve function as observed from the latency and tactile tests. The antioxidant potential of curcumol may cause its ability to ameliorate diabetes and diabetes-related complications. Curcumol, a natural metabolite with a good safety-profile, showed results comparable with tramadol in reversing diabetes-induced tactile allodynia and hyperalgesia.

Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

Science.gov (United States)

Lotfipour, Shahrdad; Smith, Maree T

2018-01-01

Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

Mechanisms of reversible photodegradation in disperse orange 11 dye doped in PMMA polymer

International Nuclear Information System (INIS)

Embaye, Natnael B.; Ramini, Shiva K.; Kuzyk, Mark G.

2008-01-01

We use amplified spontaneous emission (ASE) and linear absorption spectroscopy to study the mechanisms of reversible photodegradation of 1-amino-2-methylanthraquinone (disperse orange 11-DO11) in solid poly(methyl methacrylate). Measurements as a function of intensity, concentration, and time suggest that ASE originates in a state (be it a tautomer or a vibronic level) that can form a dimer or some other aggregate upon relaxation, which through fluorescence quenching leads to degradation of the ASE signal. Whatever the degradation route, a high concentration of DO11 is required and the polymer plays a key role in the process of opening a new reversible degradation pathway that is not available at lower concentrations or in liquid solutions. We construct an energy level diagram that describes all measured quantities in the decay and recovery processes and propose a hypothesis of the nature of the associated states

Magnetic reversals from planetary dynamo waves.

Science.gov (United States)

Sheyko, Andrey; Finlay, Christopher C; Jackson, Andrew

2016-11-24

A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines by columnar convection. Here we present an example of another class of reversing-geodynamo model, which operates in a regime of comparatively low viscosity and high magnetic diffusivity. This class does not fit into the paradigm of reversal regimes that are dictated by the value of the local Rossby number (the ratio of advection to Coriolis force). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.

Magnetization Reversal Mechanism for CoFeB Ferromagnetic Nanotube Arrays

International Nuclear Information System (INIS)

Hai-Rui, Liu; Qing-Feng, Lu; Shamaila, S.; Jun-Yang, Chen; Sharif, R.; Xiu-Feng, Han

2009-01-01

CoFeB nanotube arrays are fabricated in anodic aluminum oxide (AAO) membranes and track etched polycarbonate (PCTE) membranes by using an electrochemical method, and their magnetic properties are investigated by vibrating sample magnetometry. The coercivity H c and remanent squareness S Q of these CoFeB nanotube arrays are derived from hysteresis loops as a function of angle between the field and tube axis. The H c (θ) curves for CoFeB nanotube arrays in AAO and PCTE membranes show M-type variation, while they change shape from M to mountain-type as the tube length increases. However, the overall easy axis perpendicular to tube axis does not change with tube length. The different angular dependences are attributed to different magnetization reversal mechanisms. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)

The influence of ictal cutaneous allodynia on the response to occipital transcutaneous electrical stimulation in chronic migraine and chronic tension-type headache: a randomized, sham-controlled study.

Science.gov (United States)

Bono, F; Salvino, D; Mazza, M R; Curcio, M; Trimboli, M; Vescio, B; Quattrone, A

2015-04-01

The objective of this article is to determine whether cutaneous allodynia (CA) influences the response to treatment with occipital transcutaneous electrical stimulation (OTES) in chronic migraine (CM) and chronic tension-type headache (CTTH). One hundred and sixty consecutive patients with CM or CTTH were randomized to be treated with real or sham OTES stimulation three times a day for two consecutive weeks. All patients completed the validated 12-item allodynia symptom checklist for assessing the presence and the severity of CA during headache attack. Primary end-point was change (≥50%) in number of monthly headache-free days. There was a significant difference in the percentage of responders in the real OTES compared with sham OTES group (p headache-free days in the allodynic patients with CM and CTTH treated both with real and sham OTES, while the number of headache-free days per month was significantly reduced in the real (86%) but not in the sham group (7%) of non-allodynic patients with CTTH and CM. Severe CA is associated with decreased response to treatment with OTES in patients with CM and CTTH. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Study on the crystallographic orientation relationship and formation mechanism of reversed austenite in economical Cr12 super martensitic stainless steel

International Nuclear Information System (INIS)

Ye, Dong; Li, Shaohong; Li, Jun; Jiang, Wen; Su, Jie; Zhao, Kunyu

2015-01-01

Effect of carbides and crystallographic orientation relationship on the formation mechanism of reversed austenite of economical Cr12 super martensitic stainless steel (SMSS) has been investigated mainly by transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). The results indicate that the M_2_3C_6 precipitation and the formation of the reversed austenite have the interaction effect during tempering process in SMSS. The reversed austenite forms intensively at the sub-block boundary and the lath boundary within a misorientation range of 0–60°. M_2_3C_6 has the same crystallographic orientation relationship with reversed austenite. There are two different kinds of formation modes for reversed austenite. One is a nondiffusional shear reversion; the other is a diffusion transformation. Both are strictly limited by crystallographic orientation relationship. The austenite variants are limited to two kinds within one packet and five kinds within one prior austenite grain. - Highlights: • Reversed austenite forms at martensite boundaries with misorientation of 0–60° • M_2_3C_6 precipitation and reversed austenite formation have the interaction effect. • Two austenite variants with different orientations can be formed inside a packet. • Two reversed austenite formation modes: shear reversion; diffusion transformation

Study on the crystallographic orientation relationship and formation mechanism of reversed austenite in economical Cr12 super martensitic stainless steel

Energy Technology Data Exchange (ETDEWEB)

Ye, Dong; Li, Shaohong; Li, Jun; Jiang, Wen [Faculty of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093 (China); Su, Jie [Institute for Structural Materials, Central Iron and Steel Research Institute, Beijing 100081 (China); Zhao, Kunyu, E-mail: kyzhaoy@sina.com [Faculty of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093 (China)

2015-11-15

Effect of carbides and crystallographic orientation relationship on the formation mechanism of reversed austenite of economical Cr12 super martensitic stainless steel (SMSS) has been investigated mainly by transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). The results indicate that the M{sub 23}C{sub 6} precipitation and the formation of the reversed austenite have the interaction effect during tempering process in SMSS. The reversed austenite forms intensively at the sub-block boundary and the lath boundary within a misorientation range of 0–60°. M{sub 23}C{sub 6} has the same crystallographic orientation relationship with reversed austenite. There are two different kinds of formation modes for reversed austenite. One is a nondiffusional shear reversion; the other is a diffusion transformation. Both are strictly limited by crystallographic orientation relationship. The austenite variants are limited to two kinds within one packet and five kinds within one prior austenite grain. - Highlights: • Reversed austenite forms at martensite boundaries with misorientation of 0–60° • M{sub 23}C{sub 6} precipitation and reversed austenite formation have the interaction effect. • Two austenite variants with different orientations can be formed inside a packet. • Two reversed austenite formation modes: shear reversion; diffusion transformation.

Magnetic reversals from planetary dynamo waves

DEFF Research Database (Denmark)

Sheyko, Andrey; Finlay, Chris; Jackson, Andrew

2016-01-01

A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes ...... to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.......A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes...... place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines...

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

Science.gov (United States)

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Etiopathogenetic mechanisms of fibromyalgia syndrome

Directory of Open Access Journals (Sweden)

R.H. Gracely

2011-09-01

Full Text Available Fibromyalgia syndrome (FMS is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskel - etal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. From a pathogenetic point of view, indeed, no clear muscle pathology has been demonstrated in FMS (1, 2, while increasing evidence suggests a disturbance in pain perception that is genetically conditioned. In our review we will consider five “keypoints” that we think determine the origin and maintenance of the pain syndrome that we define as fibromyalgia...

Introduction to time reversal theory

International Nuclear Information System (INIS)

Henley, E.M.

1987-01-01

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

Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation.

Science.gov (United States)

Sharma, Neelam; Arora, Sandeep; Madan, Jitender

2018-02-01

Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

Thermodynamic restrictions on linear reversible and irreversible thermo-electro-magneto-mechanical processes

Directory of Open Access Journals (Sweden)

Sushma Santapuri

2016-10-01

Full Text Available A unified thermodynamic framework for the characterization of functional materials is developed. This framework encompasses linear reversible and irreversible processes with thermal, electrical, magnetic, and/or mechanical effects coupled. The comprehensive framework combines the principles of classical equilibrium and non-equilibrium thermodynamics with electrodynamics of continua in the infinitesimal strain regime.In the first part of this paper, linear Thermo-Electro-Magneto-Mechanical (TEMM quasistatic processes are characterized. Thermodynamic stability conditions are further imposed on the linear constitutive model and restrictions on the corresponding material constants are derived. The framework is then extended to irreversible transport phenomena including thermoelectric, thermomagnetic and the state-of-the-art spintronic and spin caloritronic effects. Using Onsager's reciprocity relationships and the dissipation inequality, restrictions on the kinetic coefficients corresponding to charge, heat and spin transport processes are derived. All the constitutive models are accompanied by multiphysics interaction diagrams that highlight the various processes that can be characterized using this framework. Keywords: Applied mathematics, Materials science, Thermodynamics

Reversal modes in asymmetric Ni nanowires

Energy Technology Data Exchange (ETDEWEB)

Leighton, B.; Pereira, A. [Departamento de Fisica, Universidad de Santiago de Chile (USACH), Avda. Ecuador 3493, 917-0124 Santiago (Chile); Escrig, J., E-mail: jescrigm@gmail.com [Departamento de Fisica, Universidad de Santiago de Chile (USACH), Avda. Ecuador 3493, 917-0124 Santiago (Chile); Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Avda. Ecuador 3493, 917-0124 Santiago (Chile)

2012-11-15

We have investigated the evolution of the magnetization reversal mechanism in asymmetric Ni nanowires as a function of their geometry. Circular nanowires are found to reverse their magnetization by the propagation of a vortex domain wall, while in very asymmetric nanowires the reversal is driven by the propagation of a transverse domain wall. The effect of shape asymmetry of the wire on coercivity and remanence is also studied. Angular dependence of the remanence and coercivity is also addressed. Tailoring the magnetization reversal mechanism in asymmetric nanowires can be useful for magnetic logic and race-track memory, both of which are based on the displacement of magnetic domain walls. Finally, an alternative method to detect the presence of magnetic drops is proposed. - Highlights: Black-Right-Pointing-Pointer Asymmetry strongly modifies the magnetic behavior of a wire. Black-Right-Pointing-Pointer Very asymmetric nanowires reverse their magnetization by a transverse domain wall. Black-Right-Pointing-Pointer An alternative method to detect the presence of magnetic drops is proposed. Black-Right-Pointing-Pointer Tailoring the reversal mode in asymmetric nanowires can be useful for potential applications.

Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.

Science.gov (United States)

Li, Dongxing; Lee, Younju; Kim, Woojin; Lee, Kyungjin; Bae, Hyunsu; Kim, Sun Kwang

2015-06-29

A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system.

Mirror reversal and visual rotation are learned and consolidated via separate mechanisms: recalibrating or learning de novo?

Science.gov (United States)

Telgen, Sebastian; Parvin, Darius; Diedrichsen, Jörn

2014-10-08

Motor learning tasks are often classified into adaptation tasks, which involve the recalibration of an existing control policy (the mapping that determines both feedforward and feedback commands), and skill-learning tasks, requiring the acquisition of new control policies. We show here that this distinction also applies to two different visuomotor transformations during reaching in humans: Mirror-reversal (left-right reversal over a mid-sagittal axis) of visual feedback versus rotation of visual feedback around the movement origin. During mirror-reversal learning, correct movement initiation (feedforward commands) and online corrections (feedback responses) were only generated at longer latencies. The earliest responses were directed into a nonmirrored direction, even after two training sessions. In contrast, for visual rotation learning, no dependency of directional error on reaction time emerged, and fast feedback responses to visual displacements of the cursor were immediately adapted. These results suggest that the motor system acquires a new control policy for mirror reversal, which initially requires extra processing time, while it recalibrates an existing control policy for visual rotations, exploiting established fast computational processes. Importantly, memory for visual rotation decayed between sessions, whereas memory for mirror reversals showed offline gains, leading to better performance at the beginning of the second session than in the end of the first. With shifts in time-accuracy tradeoff and offline gains, mirror-reversal learning shares common features with other skill-learning tasks. We suggest that different neuronal mechanisms underlie the recalibration of an existing versus acquisition of a new control policy and that offline gains between sessions are a characteristic of latter. Copyright © 2014 the authors 0270-6474/14/3413768-12$15.00/0.

Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

International Nuclear Information System (INIS)

Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

1985-01-01

Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa. (orig.)

Reversible and non-reversible enlargement of cerebral spinal fluid spaces in anorexia nervosa

Energy Technology Data Exchange (ETDEWEB)

Artmann, H.; Grau, H.; Adelmann, M.; Schleiffer, R.

1985-07-01

Brain CT studies of 35 patients with anoxia nervosa confirmed the observations of other authors: cerebral dystrophic changes correlate with weight loss and the reversibility of these changes also correlates with the normalization of body weight. Other corroborated facts are: the most numerous and most pronounced enlargements are of the cortical sulci and the interhemispheric fissure, moderate widening affects the ventricles and the rarest and most insignificant changes are those of the cerebellum. The reversibility of the changes showed a parallel to the extent of the changes themselves and to the duration of improvement of the body weight. The reversibility of the enlargement of the cortical sulci and of the distances between the frontal horns of the lateral ventricles was more often significant than that of the abnormal measurements of the cella media. This difference is based on minimal early acquired brain damage which occurs in 60% of our patients. This high incidence of early acquired minimal brain disease in patients with anorexia nervosa is here discussed as a nonspecific predisposing factor. Although there is no exact explanation of the etiology of the reversible enlargement of cerenral spinal fluid (CSF) spaces in anorexia nervosa, the changes resemble those in alcoholics. The mechanisms of brain changes in alcoholism, as shown experimentally, seem to us to throw light on the probable mechanism of reversible dystrophic brain changes in anorexia nervosa.

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

Science.gov (United States)

Lu, Kai; Gordon, Richard; Cao, Tong

2015-03-01

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in cichlid fish.

Science.gov (United States)

Lande, R; Seehausen, O; van Alphen, J J

2001-01-01

Mechanisms of speciation in cichlid fish were investigated by analyzing population genetic models of sexual selection on sex-determining genes associated with color polymorphisms. The models are based on a combination of laboratory experiments and field observations on the ecology, male and female mating behavior, and inheritance of sex-determination and color polymorphisms. The models explain why sex-reversal genes that change males into females tend to be X-linked and associated with novel colors, using the hypothesis of restricted recombination on the sex chromosomes, as suggested by previous theory on the evolution of recombination. The models reveal multiple pathways for rapid sympatric speciation through the origin of novel color morphs with strong assortative mating that incorporate both sex-reversal and suppressor genes. Despite the lack of geographic isolation or ecological differentiation, the new species coexists with the ancestral species either temporarily or indefinitely. These results may help to explain different patterns and rates of speciation among groups of cichlids, in particular the explosive diversification of rock-dwelling haplochromine cichlids.

Design and Experiment of 1LFQ-325 Pneumatic Reversible Plough

OpenAIRE

Zheng, Xuan; Chen, Xuefeng; Qin, Chaomin; Jia, Libo

2013-01-01

A pneumatic reversible plough is developed, which complements to the tractor of 25.7-36.8 kW. The plough adopts the cylinder as reversing mechanism between the right and left plough bodies, and the cylinder can substitute the mechanical reversing mechanism. The pneumatic turnover allows the plough to be operated easily and turned over flexibly. Field experiment results show that indicators of plough performance meet the requirements of the relevant national standards.

Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states.

Science.gov (United States)

Boroujerdi, Amin; Zeng, Jun; Sharp, Kelli; Kim, Donghyun; Steward, Oswald; Luo, Z David

2011-03-01

Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI-induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage-gated calcium channel alpha-2-delta-1 subunit (Ca(v)α2δ-1) proteins is effective in the management of SCI-induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Ca(v)α2δ-1 in dorsal spinal cord. To test this hypothesis, we examined whether SCI-induced dysregulation of spinal Ca(v)α2δ-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Ca(v)α2δ-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hind paw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI-induced Ca(v)α2δ-1 protein upregulation by intrathecal Ca(v)α2δ-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI-induced Ca(v)α2δ-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain states, and selectively targeting this pathway may provide effective pain relief for SCI patients. Spinal cord contusion injury caused increased calcium channel Ca(v)α2δ-1 subunit expression in dorsal spinal cord that contributes to neuropathic pain states. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Elements of a Reversible Object-Oriented Language

DEFF Research Database (Denmark)

Schultz, Ulrik Pagh; Axelsen, Holger Bock

2016-01-01

This paper presents initial ideas for the design and implementation of a reversible object-oriented language based on extending Janus with object-oriented concepts such as classes that encapsulate behavior and state, inheritance, virtual dispatching, as well as constructors. We show that virtual...... dispatching is a reversible decision mechanism easily translatable to a standard reversible programming model such as Janus, and we argue that reversible management of state can be accomplished using reversible constructors. The language is implemented in terms of translation to standard Janus programs....

Martensite phase reversion-induced nano/ ultrafine grained AISI 304L stainless steel with magnificent mechanical properties

Directory of Open Access Journals (Sweden)

Mohammad Shirdel

2015-06-01

Full Text Available Austenitic stainless steels are extensively used in various applications requiring good corrosion resistance and formability. In the current study, the formation of nano/ ultrafine grained austenitic microstructure in a microalloyed AISI 304L stainless steel was investigated by the advanced thermomechanical process of reversion of strain-induced martensite. For this purpose, samples were subjected to heavy cold rolling to produce a nearly complete martensitic structure. Subsequently, a wide range of annealing temperatures (600 to 800°C and times (1 to 240 min were employed to assess the reversion behavior and to find the best annealing condition for the production of the nano/ultrafine grained austenitic microstructure. Microstructural characterizations have been performed using X-ray diffraction (XRD, scanning electron microscopy (SEM, and magnetic measurement, whereas the mechanical properties were assessed by tensile and hardness tests. After thermomechanical treatment, a very fine austenitic structure was obtained, which was composed of nano sized grains of ~ 85 nm in an ultrafine grained matrix with an average grain size of 480 nm. This microstructure exhibited superior mechanical properties: high tensile strength of about 1280 MPa with a desirable elongation of about 41%, which can pave the way for the application of these sheets in the automotive industry.

Geomagnetic reversal rates following Palaeozoic superchrons have a fast restart mechanism.

Science.gov (United States)

Hounslow, Mark W

2016-08-30

Long intervals of single geomagnetic polarity (superchrons) reflect geodynamo processes, driven by core-mantle boundary interactions; however, it is not clear what initiates the start and end of superchrons, other than superchrons probably reflect lower heat flow across the core-mantle boundary compared with adjacent intervals. Here geomagnetic polarity timescales, with confidence intervals, are constructed before and following the reverse polarity Kiaman (Carboniferous-Permian) and Moyero (Ordovician) superchrons, providing a window into the geodynamo processes. Similar to the Cretaceous, asymmetry in reversal rates is seen in the Palaeozoic superchrons, but the higher reversal rates imply higher heatflow thresholds for entering the superchron state. Similar to the Cretaceous superchron, unusually long-duration chrons characterize the ∼10 Myr interval adjacent to the superchrons, indicating a transitional reversing state to the superchrons. This may relate to a weak pattern in the clustering of chron durations superimposed on the dominant random arrangement of chron durations.

Acidic pH facilitates peripheral αβmeATP-mediated nociception in rats: differential roles of P2X, P2Y, ASIC and TRPV1 receptors in ATP-induced mechanical allodynia and thermal hyperalgesia.

Science.gov (United States)

Seo, Hyoung-Sig; Roh, Dae-Hyun; Kwon, Soon-Gu; Yoon, Seo-Yeon; Kang, Suk-Yun; Moon, Ji-Young; Choi, Sheu-Ran; Beitz, Alvin J; Lee, Jang-Hern

2011-03-01

Peripheral ischemia is commonly associated with an increase in tissue ATP concentration and a decrease in tissue pH. Although in vitro data suggest that low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic relationship between ATP and low pH on peripheral nociception has not been fully examined. This study was designed to investigate the potential role of an acidified environment on intraplantar αβmeATP-induced peripheral pain responses in rats. The mechanical allodynia (MA) produced by injection of αβmeATP was significantly increased in animals that received the drug diluted in pH 4.0 saline compared to those that received the drug diluted in pH 7.0 saline. Moreover, animals injected with αβmeATP (100 nmol) in pH 4.0 saline developed thermal hyperalgesia (TH), which did not occur in animals treated with αβmeATP diluted in pH 7.0 saline. To elucidate which receptors were involved in this pH-related facilitation of αβmeATP-induced MA and TH, rats were pretreated with PPADS (P2 antagonist), TNP-ATP (P2X antagonist), MRS2179 (P2Y1 antagonist), AMG9810 (TRPV1 antagonist) or amiloride (ASIC blocker). Both PPADS and TNP-ATP dose-dependently blocked pH-facilitated MA, while TH was significantly reduced by pre-treatment with MRS2179 or AMG9810. Moreover, amiloride injection significantly reduced low pH-induced facilitation of αβmeATP-mediated MA, but not TH. These results demonstrate that low tissue pH facilitates ATP-mediated MA via the activation of P2X receptors and ASICs, whereas TH induced by ATP under low pH conditions is mediated by the P2Y1 receptor and TRPV1, but not ASIC. Thus distinct mechanisms are responsible for the development of MA and TH under conditions of tissue acidosis and increased ATP. Copyright © 2010 Elsevier Ltd. All rights reserved.

Thermodynamic reversibility and irreversibility of the reverse transformation in stabilized Cu-Zn-Al martensite

International Nuclear Information System (INIS)

Kustov, S.; Corro, M.; Pons, J.; Cesari, E.; Van Humbeeck, J.

2006-01-01

It has been shown that both pinning- (mechanical) and reordering-induced (chemical) stabilization components contribute to the overall stabilization effect. An algorithm has been developed for quantitative analysis of the chemical and mechanical stabilization components, using routine calorimetry results. The basic idea underlying this algorithm is that chemical and mechanical stabilization components stem, respectively, from the factors, affecting thermodynamically reversible and irreversible factors during the first reverse transformation of the stabilized martensite. On a thermodynamical level, application of the suggested algorithm has been illustrated using experimental calorimetry results for a Cu-Zn-Al alloy. Here we report analysis of pinning and reordering processes on a microscopic scale, using experimental data on non-linear anelasticity in the same Cu-Zn-Al alloy to track different spatial and temporal localization of these processes during martensite ageing

Comparison of Electroacupuncture and Morphine-Mediated Analgesic Patterns in a Plantar Incision-Induced Pain Model

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Yen-Jing Zeng

2014-01-01

Full Text Available Electroacupuncture (EA is a complementary therapy to improve morphine analgesia for postoperative pain, but underlying mechanism is not well-known. Herein, we investigated EA-induced analgesic effect in a plantar incision (PI model in male Sprague-Dawley rats. PI was performed at the left hind paw. EA of 4 Hz and high intensity or sham needling was conducted at right ST36 prior to PI and repeated for another 2 days. Behavioral responses to mechanical and thermal stimuli, spinal phospho-ERK, and Fos expression were all analyzed. In additional groups, naloxone and morphine were administered to elucidate involvement of opioid receptors and for comparison with EA. EA pretreatment significantly reduced post-PI tactile allodynia for over 1 day; repeated treatments maintained analgesic effect. Intraperitoneal naloxone could reverse EA analgesia. Low-dose subcutaneous morphine (1 mg/kg had stronger inhibitory effect on PI-induced allodynia than EA for 1 h. However, analgesic tolerance appeared after repeated morphine injections. Both EA and morphine could equally inhibit PI-induced p-ERK and Fos inductions. We conclude that though EA and morphine attenuate postincision pain through opioid receptor activations, daily EA treatments result in analgesic accumulation whereas daily morphine injections develop analgesic tolerance. Discrepant pathways and mechanisms underlying two analgesic means may account for the results.

A Novel Operant-based Behavioral Assay of Mechanical Allodynia in the Orofacial Region of Rats

Science.gov (United States)

Rohrs, Eric L.; Kloefkorn, Heidi E.; Lakes, Emily H.; Jacobs, Brittany Y.; Neubert, John K.; Caudle, Robert M.; Allen, Kyle D.

2015-01-01

Background Detecting behaviors related to orofacial pain in rodent models often relies on subjective investigator grades or methods that place the animal in a stressful environment. In this study, an operant-based behavioral assay is presented for the assessment of orofacial tactile sensitivity in the rat. New Methods In the testing chamber, rats are provided access to a sweetened condensed milk bottle; however, a 360° array of stainless steel wire loops impedes access. To receive the reward, an animal must engage the wires across the orofacial region. Contact with the bottle triggers a motor, requiring the animal to accept increasing pressure on the face during the test. To evaluate this approach, tolerated bottle distance was measured for 10 hairless Sprague-Dawley rats at baseline and 30 minutes after application of capsaicin cream (0.1%) to the face. The experiment was repeated to evaluate the ability of morphine to reverse this effect. Results The application of capsaicin cream reduced tolerated bottle distance measures relative to baseline (porofacial sensitivity is presented using an operant system. Conclusions This operant device allows for consistent measurement of heightened tactile sensitivity in the orofacial regions of the rat. PMID:25823368

Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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Couture Réjean

2010-06-01

Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

Mechanism of improving forward and reverse blocking voltages in AlGaN/GaN HEMTs by using Schottky drain

International Nuclear Information System (INIS)

Zhao Sheng-Lei; Mi Min-Han; Luo Jun; Wang Yi; Dai Yang; Zhang Jin-Cheng; Ma Xiao-Hua; Hao Yue; Hou Bin

2014-01-01

In this paper, we demonstrate that a Schottky drain can improve the forward and reverse blocking voltages (BVs) simultaneously in AlGaN/GaN high-electron mobility transistors (HEMTs). The mechanism of improving the two BVs is investigated by analysing the leakage current components and by software simulation. The forward BV increases from 72 V to 149 V due to the good Schottky contact morphology. During the reverse bias, the buffer leakage in the Ohmicdrain HEMT increases significantly with the increase of the negative drain bias. For the Schottky-drain HEMT, the buffer leakage is suppressed effectively by the formation of the depletion region at the drain terminal. As a result, the reverse BV is enhanced from −5 V to −49 V by using a Schottky drain. Experiments and the simulation indicate that a Schottky drain is desirable for power electronic applications. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Spinal SIRT1 activation attenuates neuropathic pain in mice.

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Haijun Shao

Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

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Dickenson Anthony H

2009-02-01

Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

Science.gov (United States)

Nguyen, David; Deng, Ping; Matthews, Elizabeth A; Kim, Doo-Sik; Feng, Guoping; Dickenson, Anthony H; Xu, Zao C; Luo, Z David

2009-01-01

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous

Pathological mechanism of musculoskeletal manifestations associated with CRPS type II: an animal study.

Science.gov (United States)

Ota, Hideyuki; Arai, Tetsuya; Iwatsuki, Katsuyuki; Urano, Hideki; Kurahashi, Toshikazu; Kato, Shuichi; Yamamoto, Michiro; Hirata, Hitoshi

2014-10-01

Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor β was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

[Molecular mechanism of cisplatin to enhance the ability of TRAIL in reversing multidrug resistance in gastric cancer cells].

Science.gov (United States)

Zhu, Xingchao; Zhang, Kaiguang; Wang, Qiaomin; Chen, Si; Gou, Yawen; Cui, Yufang; Li, Qin

2015-06-01

To study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in reversing multidrug resistance in vincristine-resistant human gastric cancer SGC7901/VCR cells. MTT assay was used to measure the 50% inhibiting concentration (IC₅₀) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments. SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT-PCR, RT-qPCR and Western-blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c-myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c-myc were determined by RT-PCR and Western-blot analysis. After combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC₅₀ of VCR, DDP, ADM, and 5-Fu treatment was significantly decreased compared with the control group or TRAIL-treated group (P mechanism of DDP-induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

Reversible infantile mitochondrial diseases.

Science.gov (United States)

Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

2015-05-01

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

Reverse preferential spread in complex networks

Science.gov (United States)

Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

2012-08-01

Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

Drift reversal capability in helical systems

International Nuclear Information System (INIS)

Yokoyama, M.; Itoh, K.; Okamura, S.

2002-10-01

The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

Drift reversal capability in helical systems

International Nuclear Information System (INIS)

Yokoyama, M.; Itoh, K.; Okamura, S.; Matsuoka, K.; Nakajima, N.; Itoh, S.-I.; Neilson, G.H.; Zarnstorff, M.C.; Rewoldt, G.

2003-01-01

The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

Time reversibility in the quantum frame

Energy Technology Data Exchange (ETDEWEB)

Masot-Conde, Fátima [Escuela Superior Ingenieros, Dpt. Física Aplicada III, Universidad de Sevilla Isla Mágica, 41092- Sevilla (Spain)

2014-12-04

Classic Mechanics and Electromagnetism, conventionally taken as time-reversible, share the same concept of motion (either of mass or charge) as the basis of the time reversibility in their own fields. This paper focuses on the relationship between mobile geometry and motion reversibility. The goal is to extrapolate the conclusions to the quantum frame, where matter and radiation behave just as elementary mobiles. The possibility that the asymmetry of Time (Time’s arrow) is an effect of a fundamental quantum asymmetry of elementary particles, turns out to be a consequence of the discussion.

Simulation study of self-sustainment mechanism in reversed-field pinch configuration

International Nuclear Information System (INIS)

Kusano, Kanya; Sato, Tetsuya.

1989-09-01

3D magnetohydrodynamic (MHD) simulations are carried out in order to reveal the fundamental mechanism of the self-sustainment process in the reversed-field pinch plasma. It is confirmed that the RFP configuration is sustained in a cyclic process, where the MHD relaxation phase and the resistive diffusion phase appear cyclically and alternatively. In the MHD relaxation process, the RFP plasma approaches a Taylor's minimum energy state, but it departs from there in the diffusion process. In other words, since MHD relaxation processes periodically release excess magnetic energy accumulated in the resistive diffusion phase, RFP plasma can stay in the neighborhood of the minimum energy state. The mechanism of this cyclic process is disclosed. Namely, when at least two ideal kink (m = 1) modes becomes unstable, MHD relaxation can take place. This is because the MHD relaxation progresses through nonlinear reconnection of the m = 0 mode, which is driven by nonlinear coupling between the unstable kink modes. Therefore, self-sustainment processes can be achieved by the nonlinear effects of essentially the m = 0 and 1 modes. The quantitative dependence of the relaxation-diffusion cycle on the aspect ratio of the device is considered along with its dependence on the magnetic Reynolds, number. These results are consistent with recent experiments and indicate that a coherent oscillation, which is often observed in experiments, is necessary for self-sustainment. The influence of self-sustainment processes on particle confinement is briefly discussed. (author)

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

Science.gov (United States)

Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal

2014-02-01

This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

Magnetization reversal mechanism and coercivity enhancement in three-dimensional granular Nd-Fe-B magnets studied by micromagnetic simulations

Science.gov (United States)

Lee, Jae-Hyeok; Choe, Jinhyeok; Hwang, Shinwon; Kim, Sang-Koog

2017-08-01

We studied the mechanism of magnetization reversals and coercivity enhancements in three-dimensional (3D) granular Nd-Fe-B permanent magnets using finite-element micromagnetic simulations. The magnetization reversals in the hard magnets consisting of hard-phase grains separated by relatively soft-phase grain boundaries were analyzed with reference to the simulation results for the magnetic field-dependent distributions of the local magnetizations. The saturation magnetization of the grain-boundary phase plays a crucial role in the transition between nucleation- and domain-wall-propagation-controlled reversal processes. The smaller the saturation magnetization of the grain-boundary phase is, the more preferable is the nucleation-controlled process, which results in a larger coercivity. The exchange stiffness of the grain-boundary phase determines the preferred paths of domain-wall propagations, whether inward into grains or along the grain boundaries for relatively small and large exchange stiffness, respectively. However, the exchange stiffness of the grain-boundary phase alone does not significantly contribute to coercivity enhancement in cases where the size of hard-phase grains is much greater than the exchange length. This work paves the way for the design of high-performance hard magnets of large coercivity and maximum-energy-product values.

Reverse remodeling and the mechanism of mitral regurgitation improvement in patients with dilated cardiomyopathy.

Science.gov (United States)

Kuperstein, Rafael; Blechman, Ido; Ben Zekry, Sagit; Klempfner, Robert; Freimark, Dov; Arad, Michael

2015-01-01

Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

Directory of Open Access Journals (Sweden)

Laurence Meyer

Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

Kinetic Line Voronoi Operations and Their Reversibility

DEFF Research Database (Denmark)

Mioc, Darka; Anton, François; Gold, Christopher

2010-01-01

In Geographic Information Systems the reversibility of map update operations has not been explored yet. In this paper we are using the Voronoi based Quad-edge data structure to define reversible map update operations. The reversibility of the map operations has been formalised at the lowest level...... mechanisms and dynamic map visualisations. In order to use the reversibility within the kinetic Voronoi diagram of points and open oriented line segments, we need to assure that reversing the map commands will produce exactly the changes in the map equivalent to the previous map states. To prove...... that reversing the map update operations produces the exact reverse changes, we show an isomorphism between the set of complex operations on the kinetic Voronoi diagram of points and open oriented line segments and the sets of numbers of new / deleted Voronoi regions induced by these operations, and its...

Reflex mechanisms in CRPS-related dystonia

NARCIS (Netherlands)

Mugge, W.

2011-01-01

Complex Regional Pain Syndrome (CRPS) is a disabling syndrome associated with sensory (e.g., burning pain, allodynia, hyperalgesia), autonomic (e.g., edema, skin color and temperature changes), and motor impairments (e.g., tremor, myoclonus, dystonia). Approximately 25% of the patients with CRPS

Magnetization reversal mechanisms in hybrid resin-bonded Nd Fe B magnets

Science.gov (United States)

Plusa, D.; Dospial, M.; Slusarek, B.; Kotlarczyk, U.

2006-11-01

The magnetic properties of isotropic epoxy resin-bonded magnets prepared by mixing a hard magnetic powder made from melt quenched Nd-Fe-Co-B ribbons and a soft magnetic iron powder have been examined. The magnetization reversal processes and the magnetic parameters have been studied by the measurement of the virgin magnetization curves, the major and minor hysteresis loops and sets of recoil curves. From these recoil curves the field dependence of the reversible and irreversible magnetization components during the magnetization and demagnetization processes has been derived. The remanence relationship was used to study the nature of magnetic interaction between the grains. A study of interaction domains was conducted using optical microscopy. Groups of domains, each over several grains, were observed. It was found that the reversal process in the samples investigated involves the rotation of magnetization vectors in the iron powder grains and pinning of domain walls at the MQP-B grain boundaries.

Magnetization reversal mechanisms in hybrid resin-bonded Nd-Fe-B magnets

International Nuclear Information System (INIS)

Plusa, D.; Dospial, M.; Slusarek, B.; Kotlarczyk, U.

2006-01-01

The magnetic properties of isotropic epoxy resin-bonded magnets prepared by mixing a hard magnetic powder made from melt quenched Nd-Fe-Co-B ribbons and a soft magnetic iron powder have been examined. The magnetization reversal processes and the magnetic parameters have been studied by the measurement of the virgin magnetization curves, the major and minor hysteresis loops and sets of recoil curves. From these recoil curves the field dependence of the reversible and irreversible magnetization components during the magnetization and demagnetization processes has been derived. The remanence relationship was used to study the nature of magnetic interaction between the grains. A study of interaction domains was conducted using optical microscopy. Groups of domains, each over several grains, were observed. It was found that the reversal process in the samples investigated involves the rotation of magnetization vectors in the iron powder grains and pinning of domain walls at the MQP-B grain boundaries

Reversal mechanisms and interactions in magnetic systems: coercivity versus switching field and thermally assisted demagnetization

Directory of Open Access Journals (Sweden)

Cebollada, F.

2005-06-01

Full Text Available In this paper we present a comparative analysis of the magnetic interactions and reversal mechanisms of two different systems: NdFeB-type alloys with grain sizes in the single domain range and Fe-SiO2 nanocomposites with Fe concentrations above and below the percolation threshold. We evidence that the use of the coercivity as the main parameter to analyse them might be misleading due to the convolution of both reversible and irreversible magnetization variations. We show that the switching field and thermally assisted demagnetization allow a better understanding of these mechanisms since they involve just irreversible magnetization changes. Specifically, the experimental analysis of the coercivity adquisition process for the NdFeB-type system suggests that the magnetization reversal is nucleated at the spin misalignments present due to intergranular exchange interactions. On the other hand, the study of the magnetic viscosity and of the isothermal remanent magnetization (IRM and direct field demagnetization (DCD remanence curves indicates that the dipolar interactions are responsible for the propagation of the switching started at individual particles.

En este artículo presentamos un análisis comparativo de la influencia de la microestructura a través de las interacciones magnéticas en los mecanismos de inversión de la magnetización en dos sistemas diferentes: aleaciones tipo NdFeB con tamaños de grano en el rango de monodominio y nanocompuestos de Fe-SiO2 con concentraciones de Fe tanto por encima como por debajo del umbral de percolación. Ponemos de manifiesto que el uso del campo coercitivo como parámetro de análisis puede llevar a equívocos debido a la coexistencia de variaciones reversibles e irreversibles de la magnetización. También mostramos que el campo de conmutación y la desimanación térmicamente asistida permiten una mejor comprensión de dichos mecanismos ya que reflejan exclusivamente cambios irreversibles de

Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

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Enrique J. Cobos

2018-01-01

Full Text Available Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.

Reversible perspective and splitting in time.

Science.gov (United States)

Hart, Helen Schoenhals

2012-01-01

The element of time--the experience of it and the defensive use of it--is explored in conjunction with the use of reversible perspective as a psychotic defense. Clinical material from a long analysis illustrates how a psychotic patient used the reversible perspective, with its static splitting, to abolish the experience of time. When he improved and the reversible perspective became less effective for him, he replaced it with a more dynamic splitting mechanism using time gaps. With further improvement, the patient began to experience the passage of time, and along with it the excruciating pain of separation, envy, and loss.

Influence of prior cold rolling reduction on microstructure and mechanical properties of a reversion annealed high-Mn austenitic steel

Energy Technology Data Exchange (ETDEWEB)

Behjati, P., E-mail: p.behjatipournaki@ma.iut.ac.ir [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Kermanpur, A. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Karjalainen, L.P.; Järvenpää, A.; Jaskari, M. [Centre for Advanced Steels Research, University of Oulu, FIN-90014 Oulu (Finland); Samaei Baghbadorani, H. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Najafizadeh, A. [Foulad Institute of Technology, Fouladshahr, Isfahan 84916-63763 (Iran, Islamic Republic of); Hamada, A. [Metallurgical and Materials Engineering Department, Faculty of Petroleum and Mining Engineering, Suez University, Suez 43721 (Egypt)

2016-01-05

The martensitic reversion is known to be effective in refining the grain size of metastable austenitic stainless steels. However, severe cold rolling reductions are generally required for this process. In this study, the influence of the degree of prior cold rolling and subsequent annealing on the microstructure and mechanical properties of a metastable high-Mn austenitic steel was investigated. Three cold rolling reductions of 20%, 35% and 50% were applied at ambient temperature before the annealing at 700 °C for the durations of 10, 100 and 1000 s. Microstructures were examined by optical, scanning and transmission electron microscopes. Mechanical properties were measured by hardness and tensile tests. The microstructure changes were followed by magnetic measurements and X-ray diffraction. It was shown that a relatively small reduction of 35% and 100 s annealing could provide efficient grain refinement (the average size of 0.5 µm) and accordingly an outstanding combination of strength-ductility properties with the yield strength 890 MPa, tensile strength 1340 MPa and elongation 41% was achieved. The occurrence of martensite reversion and recrystallization processes with different contributions in dependence on degree of prior deformation before annealing was discussed.

An easily reversible structural change underlies mechanisms enabling desert crust cyanobacteria to survive desiccation.

Science.gov (United States)

Bar-Eyal, Leeat; Eisenberg, Ido; Faust, Adam; Raanan, Hagai; Nevo, Reinat; Rappaport, Fabrice; Krieger-Liszkay, Anja; Sétif, Pierre; Thurotte, Adrien; Reich, Ziv; Kaplan, Aaron; Ohad, Itzhak; Paltiel, Yossi; Keren, Nir

2015-10-01

Biological desert sand crusts are the foundation of desert ecosystems, stabilizing the sands and allowing colonization by higher order organisms. The first colonizers of the desert sands are cyanobacteria. Facing the harsh conditions of the desert, these organisms must withstand frequent desiccation-hydration cycles, combined with high light intensities. Here, we characterize structural and functional modifications to the photosynthetic apparatus that enable a cyanobacterium, Leptolyngbya sp., to thrive under these conditions. Using multiple in vivo spectroscopic and imaging techniques, we identified two complementary mechanisms for dissipating absorbed energy in the desiccated state. The first mechanism involves the reorganization of the phycobilisome antenna system, increasing excitonic coupling between antenna components. This provides better energy dissipation in the antenna rather than directed exciton transfer to the reaction center. The second mechanism is driven by constriction of the thylakoid lumen which limits diffusion of plastocyanin to P700. The accumulation of P700(+) not only prevents light-induced charge separation but also efficiently quenches excitation energy. These protection mechanisms employ existing components of the photosynthetic apparatus, forming two distinct functional modes. Small changes in the structure of the thylakoid membranes are sufficient for quenching of all absorbed energy in the desiccated state, protecting the photosynthetic apparatus from photoinhibitory damage. These changes can be easily reversed upon rehydration, returning the system to its high photosynthetic quantum efficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid and reversible impairments of short- and long-term social recognition memory are caused by acute isolation of adult rats via distinct mechanisms.

Science.gov (United States)

Shahar-Gold, Hadar; Gur, Rotem; Wagner, Shlomo

2013-01-01

Mammalian social organizations require the ability to recognize and remember individual conspecifics. This social recognition memory (SRM) can be examined in rodents using their innate tendency to investigate novel conspecifics more persistently than familiar ones. Here we used the SRM paradigm to examine the influence of housing conditions on the social memory of adult rats. We found that acute social isolation caused within few days a significant impairment in acquisition of short-term SRM of male and female rats. Moreover, SRM consolidation into long-term memory was blocked following only one day of social isolation. Both impairments were reversible, but with different time courses. Furthermore, only the impairment in SRM consolidation was reversed by systemic administration of arginine-vasopressin (AVP). In contrast to SRM, object recognition memory was not affected by social isolation. We conclude that acute social isolation rapidly induces reversible changes in the brain neuronal and molecular mechanisms underlying SRM, which hamper its acquisition and completely block its consolidation. These changes occur via distinct, AVP sensitive and insensitive mechanisms. Thus, acute social isolation of rats swiftly causes changes in their brain and interferes with their normal social behavior.

Rapid and reversible impairments of short- and long-term social recognition memory are caused by acute isolation of adult rats via distinct mechanisms.

Directory of Open Access Journals (Sweden)

Hadar Shahar-Gold

Full Text Available Mammalian social organizations require the ability to recognize and remember individual conspecifics. This social recognition memory (SRM can be examined in rodents using their innate tendency to investigate novel conspecifics more persistently than familiar ones. Here we used the SRM paradigm to examine the influence of housing conditions on the social memory of adult rats. We found that acute social isolation caused within few days a significant impairment in acquisition of short-term SRM of male and female rats. Moreover, SRM consolidation into long-term memory was blocked following only one day of social isolation. Both impairments were reversible, but with different time courses. Furthermore, only the impairment in SRM consolidation was reversed by systemic administration of arginine-vasopressin (AVP. In contrast to SRM, object recognition memory was not affected by social isolation. We conclude that acute social isolation rapidly induces reversible changes in the brain neuronal and molecular mechanisms underlying SRM, which hamper its acquisition and completely block its consolidation. These changes occur via distinct, AVP sensitive and insensitive mechanisms. Thus, acute social isolation of rats swiftly causes changes in their brain and interferes with their normal social behavior.

Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

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Mao-yin Zhang

2015-01-01

Full Text Available Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI. Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg were administrated intragastrically at early phase of postoperation (before pain appearance and later phase of postoperation (after pain appearance, respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

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Ouyang Handong

2011-05-01

Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.

Science.gov (United States)

Tamaddonfard, Esmaeal; Farshid, Amir-Abbas; Eghdami, Karim; Samadi, Farzad; Erfanparast, Amir

2013-01-01

Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.

Compound nucleus studies withy reverse kinematics

International Nuclear Information System (INIS)

Moretto, L.G.

1985-06-01

Reverse kinematics reactions are used to demonstrate the compound nucleus origin of intermediate mass particles at low energies and the extension of the same mechanism at higher energies. No evidence has appeared in our energy range for liquid-vapor equilibrium or cold fragmentation mechanisms. 11 refs., 12 figs

Reversal learning as a measure of impulsive and compulsive behavior in addictions.

Science.gov (United States)

Izquierdo, Alicia; Jentsch, J David

2012-01-01

Our ability to measure the cognitive components of complex decision-making across species has greatly facilitated our understanding of its neurobiological mechanisms. One task in particular, reversal learning, has proven valuable in assessing the inhibitory processes that are central to executive control. Reversal learning measures the ability to actively suppress reward-related responding and to disengage from ongoing behavior, phenomena that are biologically and descriptively related to impulsivity and compulsivity. Consequently, reversal learning could index vulnerability for disorders characterized by impulsivity such as proclivity for initial substance abuse as well as the compulsive aspects of dependence. Though we describe common variants and similar tasks, we pay particular attention to discrimination reversal learning, its supporting neural circuitry, neuropharmacology and genetic determinants. We also review the utility of this task in measuring impulsivity and compulsivity in addictions. We restrict our review to instrumental, reward-related reversal learning studies as they are most germane to addiction. The research reviewed here suggests that discrimination reversal learning may be used as a diagnostic tool for investigating the neural mechanisms that mediate impulsive and compulsive aspects of pathological reward-seeking and -taking behaviors. Two interrelated mechanisms are posited for the neuroadaptations in addiction that often translate to poor reversal learning: frontocorticostriatal circuitry dysregulation and poor dopamine (D2 receptor) modulation of this circuitry. These data suggest new approaches to targeting inhibitory control mechanisms in addictions.

Reversibility of female sterilization.

Science.gov (United States)

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

1985-04-01

results of SR according to the original sterilization procedure. The most commonly performed sterilization (Pomeroy) was the most frequently reported to have undergone a reversal attempt, with a 50% success rate based on term or intrauterine pregnancies. Electrocoagulation was the next most frequent technique for reversal, with a 41% success rate. The less destrictive mechanical tehcniques, clip and band, had a reversal rate of 84% and 72%, respectively. A table summarizes sterilization procedures devised for reversibility in women. A women seeking sterilization should be advised that sterilization is permanent if no further tubal surgery is performed and that reversal is possible but involves a major and expensive operation.

The Reverse Supply Chain: Configuration, Integration and Profitability

DEFF Research Database (Denmark)

Gobbi, Chiara

2008-01-01

This thesis presents the results of a qualitative investigation that has been conducted in order to enhance knowledge of the reverse supply chain management field. Two aspects of the reverse flow need to be taken into consideration: the importance of introducing mechanisms that promote the circui......This thesis presents the results of a qualitative investigation that has been conducted in order to enhance knowledge of the reverse supply chain management field. Two aspects of the reverse flow need to be taken into consideration: the importance of introducing mechanisms that promote...... the circuitry of resources in order to protect the environment, and the increasing awareness that if strategically managed, the reverse chain represents an opportunity for profit generation and for improving the competitive position of a firm. In the first case, the main stakeholders are represented...... within the 27 Member States, reaching approximately 14-24 Kg. per inhabitant in Western Europe and the 6-12 Kg. per inhabitant in the New Member States. In the second case, the main stakeholder is the firm, the producer that has the possibility of exploring new opportunities to achieve a competitive...

Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice

Science.gov (United States)

Crowe, Molly S; Leishman, Emma; Banks, Matthew L; Gujjar, Ramesh; Mahadevan, Anu; Bradshaw, Heather B; Kinsey, Steven G

2015-01-01

Background and Purpose Neuropathic pain is commonly treated with GABA analogues, steroids or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or more COX isozymes but chronic COX inhibition paradoxically increases gastrointestinal inflammation and risk of unwanted cardiovascular events. The cannabinoids also have analgesic and anti-inflammatory properties and reduce neuropathic pain in animal models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using low doses of both inhibitors. Experimental Approach Mice subjected to chronic constriction injury (CCI) were tested for mechanical and cold allodynia after administration of the MAGL inhibitor, JZL184, or the non-selective COX inhibitor diclofenac. Then, both drugs were co-administered at fixed dose proportions of 1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related lipids were quantified in lumbar spinal cord. Key Results Combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic effects of the JZL184 and diclofenac combination on mechanical allodynia, implying that CB1 receptors were primarily responsible for the anti-allodynia. Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2α in lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in the endocannabinoid metabolite, N-arachidonoyl glycine. Conclusions and Implications Combining COX and MAGL inhibition is a promising therapeutic approach for reducing neuropathic pain with minimal side effects. PMID:25393148

Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

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Hulse Richard P

2012-06-01

Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

Magnetization reversal modes in fourfold Co nano-wire systems

International Nuclear Information System (INIS)

Blachowicz, T; Ehrmann, A

2015-01-01

Magnetic nano-wire systems are, as well as other patterned magnetic structures, of special interest for novel applications, such as magnetic storage media. In these systems, the coupling between neighbouring magnetic units is most important for the magnetization reversal process of the complete system, leading to a variety of magnetization reversal mechanisms. This article examines the influence of the magnetic material on hysteresis loop shape, coercive field, and magnetization reversal modes. While iron nano-wire systems exhibit flat or one-step hysteresis loops, systems consisting of cobalt nano-wires show hysteresis loops with several longitudinal steps and transverse peaks, correlated to a rich spectrum of magnetization reversal mechanisms. We show that changing the material parameters while the system geometry stays identical can lead to completely different hysteresis loops and reversal modes. Thus, especially for finding magnetic nano-systems which can be used as quaternary or even higher-order storage devices, it is rational to test several materials for the planned systems. Apparently, new materials may lead to novel and unexpected behaviour - and can thus result in novel functionalities. (paper)

Magnetization reversal modes in fourfold Co nano-wire systems

Science.gov (United States)

Blachowicz, T.; Ehrmann, A.

2015-09-01

Magnetic nano-wire systems are, as well as other patterned magnetic structures, of special interest for novel applications, such as magnetic storage media. In these systems, the coupling between neighbouring magnetic units is most important for the magnetization reversal process of the complete system, leading to a variety of magnetization reversal mechanisms. This article examines the influence of the magnetic material on hysteresis loop shape, coercive field, and magnetization reversal modes. While iron nano-wire systems exhibit flat or one-step hysteresis loops, systems consisting of cobalt nano-wires show hysteresis loops with several longitudinal steps and transverse peaks, correlated to a rich spectrum of magnetization reversal mechanisms. We show that changing the material parameters while the system geometry stays identical can lead to completely different hysteresis loops and reversal modes. Thus, especially for finding magnetic nano-systems which can be used as quaternary or even higher-order storage devices, it is rational to test several materials for the planned systems. Apparently, new materials may lead to novel and unexpected behaviour - and can thus result in novel functionalities.

ON THE ANALYSIS OF IMPEDANCE-DRIVEN REVERSE FLOW DYNAMICS

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LEE V. C.-C.

2017-02-01

Full Text Available Impedance pump is a simple valve-less pumping mechanism, where an elastic tube is joined to a more rigid tube, at both ends. By inducing a periodic asymmetrical compression on the elastic tube will produce a unidirectional flow within the system. This pumping concept offers a low energy, low noise alternative, which makes it an effective driving mechanism, especially for micro-fluidic systems. In addition, the wave-based mechanism through which pumping occurs infers many benefits in terms of simplicity of design and manufacturing. Adjustment of simple parameters such as the excitation frequencies or compression locations will reverse the direction of flow, providing a very versatile range of flow outputs. This paper describes the experimental analysis of such impedance-driven flow with emphasis on the dynamical study of the reverse flow in open-loop environment. In this study, tapered section with converging steps is introduced at both ends of the elastic tube to amplify the magnitude of reverse flow. Study conducted shows that the reverse peak flow is rather significant with estimate of 23% lower than the forward peak flow. The flow dynamics on the other hand has shown to exhibit different characteristics as per the forward peak flow. The flow characteristics is then studied and showed that the tapered sections altered the impedance within the system and hence induce a higher flow in the reverse direction.

Supramolecular Cross-Links in Poly(alkyl methacrylate) Copolymers and Their Impact on the Mechanical and Reversible Adhesive Properties.

Science.gov (United States)

Heinzmann, Christian; Salz, Ulrich; Moszner, Norbert; Fiore, Gina L; Weder, Christoph

2015-06-24

Hydrogen-bonded, side-chain-functionalized supramolecular poly(alkyl methacrylate)s were investigated as light- and temperature-responsive reversible adhesives that are useful for bonding and debonding on demand applications. Here, 2-hydroxyethyl methacrylate (HEMA) was functionalized with 2-ureido-4[1H]pyrimidinone (UPy) via a hexamethylenediisocyanate (HMDI) linker, to create a monomer (UPy-HMDI-HEMA) that serves to form supramolecular cross-links by way of forming quadruple hydrogen bonded dimers. UPy-HMDI-HEMA was copolymerized with either hexyl methacrylate or butyl methacrylate to create copolymers comprising 2.5, 5, or 10 mol % of the cross-linker. The mechanical properties of all (co)polymers were investigated with stress-strain experiments and dynamic mechanical analysis. Furthermore, the adhesive properties were studied at temperatures between 20 and 60 °C by testing single lap joints formed with stainless steel substrates. It was found that increasing the concentration of the UPy-HMDI-HEMA cross-linker leads to improved mechanical and adhesive properties at elevated temperatures. Concurrently, the reversibility of the bond formation remained unaffected, where rebonded samples displayed the same adhesive strength as regularly bonded samples. Debonding on demand abilities were also tested exemplarily for one copolymer, which for light-induced debonding experiments was blended with a UV-absorber that served as light-heat converter. Single lap joints were subjected to a constant force and heated or irradiated with UV light until debonding occurred. The necessary debonding temperature was comparable for direct heating and UV irradiation and varied between 28 and 82 °C, depending on the applied force. The latter also influenced the debonding time, which under the chosen conditions ranged from 30 s to 12 min.

Ice ages and geomagnetic reversals

Science.gov (United States)

Wu, Patrick

1992-01-01

There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

Alcohol consumption stimulates early stemps in reverse cholesterol transport

NARCIS (Netherlands)

Gaag, van der M.S.; Tol, van A.; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

2001-01-01

Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

Alcohol consumption stimulates early steps in reverse cholesterol transport

NARCIS (Netherlands)

Gaag, M.S. van der; Tol, A. van; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

2001-01-01

Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

The physics of reversed-field pinch profile sustainment

International Nuclear Information System (INIS)

Moses, R.W.

1985-01-01

A description of the Reversed-Field Pinch (RFP) is given. There is experimental evidence that indicates that an RFP dynamo effect sustains field reversal in steady state. Three sustainment mechanisms are reviewed: the MHD model, the tangled discharge model, and the kinetic dynamo model. The relationship of these models to each another is discussed briefly

Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice.

Science.gov (United States)

Zhang, Linlin; Terrando, Niccolò; Xu, Zhen-Zhong; Bang, Sangsu; Jordt, Sven-Eric; Maixner, William; Serhan, Charles N; Ji, Ru-Rong

2018-01-01

Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP). Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia). In contrast, post-operative intrathecal (IT) administration of DHA (500 μg) 2 weeks after the surgery had no effects on established mechanical and cold allodynia. However, by direct comparison, IT post-operative treatment (500 ng) with neuroprotectin D1 (NPD1), MaR1, and D-resolvins, RvD1 and RvD5, but not RvD3 and RvD4, effectively reduced mechanical and cold allodynia. ELISA analysis showed that perioperative DHA treatment increased RvD1 levels in serum and spinal cord samples after bone fracture. Interestingly, sham surgery resulted in transient allodynia and increased RvD1 levels, suggesting a correlation of enhanced SPM levels with acute pain resolution after sham surgery. Our findings suggest that (1) perioperative treatment with DHA is effective in preventing and delaying the development of fPOP and (2) post-treatment with some SPMs can attenuate established fPOP. Our data also indicate that orthopedic surgery impairs SPM production. Thus, DHA and DHA-derived SPMs should be differentially supplemented for treating fPOP and improving recovery.

Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice

Directory of Open Access Journals (Sweden)

Linlin Zhang

2018-05-01

Full Text Available Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs, derived from fish oil docosahexaenoic acid (DHA, promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP. Intravenous perioperative treatment with DHA (500 μg, resolvin D1 (RvD1, 500 ng and maresin 1 (MaR1, 500 ng, 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia. In contrast, post-operative intrathecal (IT administration of DHA (500 μg 2 weeks after the surgery had no effects on established mechanical and cold allodynia. However, by direct comparison, IT post-operative treatment (500 ng with neuroprotectin D1 (NPD1, MaR1, and D-resolvins, RvD1 and RvD5, but not RvD3 and RvD4, effectively reduced mechanical and cold allodynia. ELISA analysis showed that perioperative DHA treatment increased RvD1 levels in serum and spinal cord samples after bone fracture. Interestingly, sham surgery resulted in transient allodynia and increased RvD1 levels, suggesting a correlation of enhanced SPM levels with acute pain resolution after sham surgery. Our findings suggest that (1 perioperative treatment with DHA is effective in preventing and delaying the development of fPOP and (2 post-treatment with some SPMs can attenuate established fPOP. Our data also indicate that orthopedic surgery impairs SPM production. Thus, DHA and DHA-derived SPMs should be differentially supplemented for treating fPOP and improving recovery.

Two-photon fluorescent polysiloxane-based films with thermally responsive self switching properties achieved by a unique reversible spirocyclization mechanism.

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Zuo, Yujing; Yang, Tingxin; Zhang, Yu; Gou, Zhiming; Tian, Minggang; Kong, Xiuqi; Lin, Weiying

2018-03-14

Responsiveness and reversibility are present in nature, and are ubiquitous in biological systems. The realization of reversibility and responsiveness is of great importance in the development of properties and the design of new materials. However, two-photon fluorescent thermal-responsive materials have not been reported to date. Herein, we engineered thermally responsive polysiloxane materials ( Dns-non ) that exhibited unique two-photon luminescence, and this is the first report about thermally responsive luminescent materials with two-photon fluorescence. The fluorescence of Dns-non could switch from the "on" to "off" state through a facile heating and cooling process, which could be observed by the naked eye. Monitoring the temperature of the CPU in situ was achieved by easily coating D1-non onto the CPU surface, which verified the potential application in devices of Dns-non . A unique alkaline tuned reversible transition mechanism of rhodamine-B from its spirocyclic to its ring-open state was proposed. Furthermore, Dns-non appeared to be a useful cell adhesive for the culture of cells on the surface. We believe that the constructed thermally responsive silicon films which have promising utilization as a new type of functional fluorescent material, may show broad applications in materials chemistry or bioscience.

Nature of unstable insertional mutations and reversions at the cut locus of Drosophila melanogaster: Molecular mechanism for transpositional memory

International Nuclear Information System (INIS)

Mizrokhi, L.Yu.; Georgieva, S.G.; Obolenkova, L.A.; Priimyagi, A.F.; Gerasimova, T.I.; Il'in, Yu.V.

1988-01-01

A segment of the cut locus containing an mdg4 insertion as a result of ct MR and ct MRp10 mutations was cloned. Clones were obtained for the phenotypically different ct MR2 and ct MRpN10 mutants and for stable and unstable revertants. All mutations studied are associated with mdg4 insertion at an identical nucleotide sequence of the cut locus, the same site at which mdg4 is inserted at the ct 6 allele. The ct MRpN line differs from ct MR2 in that the mobile element jockey (3 kbp) is inserted in mdg4. Jockey is represented by about 1,000 copies per genome; it is homogeneous and lacks long terminal repeats (LTRs). In stable ct + reversions, mdg4 is completely excised. In unstable ct + reversions, in which there is a high degree of reverse directed transposition of mdg4 to the cut locus, an LTR of mdg4 is preserved at the site of the mutation. It is a sequence along which new copies of mdg4 or jockey-containing mdg4 are inserted into the genome. The authors discuss a molecular mechanism for transpositional memory involving homologous recombination of the remnant LTR and circular extrachromosomal copies of mdg4

Time reversibility, computer simulation, algorithms, chaos

CERN Document Server

Hoover, William Graham

2012-01-01

A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful vocabulary and a set of concepts, which allow a fuller explanation of irreversibility than that available to Boltzmann or to Green, Kubo and Onsager. Clear illustration of concepts is emphasized throughout, and reinforced with a glossary of technical terms from the specialized fields which have been combined here to focus on a common theme. The book begins with a discussion, contrasting the idealized reversibility of ba...

Anti-allodynic effects of N-demethylsinomenine, an active metabolite of sinomenine, in a mouse model of postoperative pain.

Science.gov (United States)

Ou, Yuntao; Su, Man; Ling, Yong; Wei, Qianqian; Pan, Fei; Li, Jiejia; Li, Jun-Xu; Zhu, Qing

2018-03-15

Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N-demethylsinomenine (10-40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N-demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N-demethylsinomenine was quicker than sinomenine. Repeated treatment with N-demethylsinomenine (10-40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N-demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline, a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist. In addition, the doses of N-demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N-demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABA A receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

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Liu Huaqing

2012-06-01

Full Text Available Abstract Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia. The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI, are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1�

Immunodominant fragments of myelin basic protein initiate T cell-dependent pain.

Science.gov (United States)

Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

2012-06-07

The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia

A novel and selective poly (ADP-ribose polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

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Lauren E Ta

Full Text Available Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose polymerase (PARP inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888 would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice.An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p. injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment.Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

A novel and selective poly (ADP-ribose) polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

Science.gov (United States)

Ta, Lauren E; Schmelzer, James D; Bieber, Allan J; Loprinzi, Charles L; Sieck, Gary C; Brederson, Jill D; Low, Philip A; Windebank, Anthony J

2013-01-01

Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice. An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment. Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

Sex Reversal in Birds.

Science.gov (United States)

Major, Andrew T; Smith, Craig A

2016-01-01

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

Proteome and Transcriptome Analysis of Ovary, Intersex Gonads, and Testis Reveals Potential Key Sex Reversal/Differentiation Genes and Mechanism in Scallop Chlamys nobilis.

Science.gov (United States)

Shi, Yu; Liu, Wenguang; He, Maoxian

2018-04-01

Bivalve mollusks exhibit hermaphroditism and sex reversal/differentiation. Studies generally focus on transcriptional profiling and specific genes related to sex determination and differentiation. Few studies on sex reversal/differentiation have been reported. A combination analysis of gonad proteomics and transcriptomics was conducted on Chlamys nobilis to provide a systematic understanding of sex reversal/differentiation in bivalves. We obtained 4258 unique peptides and 93,731 unigenes with good correlation between messenger RNA and protein levels. Candidate genes in sex reversal/differentiation were found: 15 genes differentially expressed between sexes were identified and 12 had obvious sexual functions. Three novel genes (foxl2, β-catenin, and sry) were expressed highly in intersex individuals and were likely involved in the control of gonadal sex in C. nobilis. High expression of foxl2 or β-catenin may inhibit sry and activate 5-HT receptor and vitellogenin to maintain female development. High expression of sry may inhibit foxl2 and β-catenin and activate dmrt2, fem-1, sfp2, sa6, Amy-1, APCP4, and PLK to maintain male function. High expression of sry, foxl2, and β-catenin in C. nobilis may be involved in promoting and maintaining sex reversal/differentiation. The downstream regulator may not be dimorphic expressed genes, but genes expressed in intersex individuals, males and females. Different expression patterns of sex-related genes and gonadal histological characteristics suggested that C. nobilis may change its sex from male to female. These findings suggest highly conserved sex reversal/differentiation with diverged regulatory pathways during C. nobilis evolution. This study provides valuable genetic resources for understanding sex reversal/differentiation (intersex) mechanisms and pathways underlying bivalve reproductive regulation.

Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

Science.gov (United States)

Nashawi, Houda; Masocha, Willias; Edafiogho, Ivan O; Kombian, Samuel B

The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system. One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. The paclitaxel-treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel-treated rats produced a significantly higher maximal response (Emax) than those from untreated rats (p GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax in slices from untreated rats (p GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain (PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP. © 2016 S. Karger AG, Basel.

Reverse blocking characteristics and mechanisms in Schottky-drain AlGaN/GaN HEMT with a drain field plate and floating field plates

International Nuclear Information System (INIS)

Mao Wei; She Wei-Bo; Zhang Jin-Feng; Zheng Xue-Feng; Wang Chong; Hao Yue; Yang Cui

2016-01-01

In this paper, a novel AlGaN/GaN HEMT with a Schottky drain and a compound field plate (SD-CFP HEMT) is presented for the purpose of better reverse blocking capability. The compound field plate (CFP) consists of a drain field plate (DFP) and several floating field plates (FFPs). The physical mechanisms of the CFP to improve the reverse breakdown voltage and to modulate the distributions of channel electric field and potential are investigated by two-dimensional numerical simulations with Silvaco-ATLAS. Compared with the HEMT with a Schottky drain (SD HEMT) and the HEMT with a Schottky drain and a DFP (SD-FP HEMT), the superiorities of SD-CFP HEMT lie in the continuous improvement of the reverse breakdown voltage by increasing the number of FFPs and in the same fabrication procedure as the SD-FP HEMT. Two useful optimization laws for the SD-CFP HEMTs are found and extracted from simulation results. The relationship between the number of the FFPs and the reverse breakdown voltage as well as the FP efficiency in SD-CFP HEMTs are discussed. The results in this paper demonstrate a great potential of CFP for enhancing the reverse blocking ability in AlGaN/GaN HEMT and may be of great value and significance in the design and actual manufacture of SD-CFP HEMTs. (paper)

Martensite shear phase reversion-induced nanograined/ultrafine-grained Fe-16Cr-10Ni alloy: The effect of interstitial alloying elements and degree of austenite stability on phase reversion

Energy Technology Data Exchange (ETDEWEB)

Misra, R.D.K., E-mail: dmisra@louisiana.edu [Center for Structural and Functional Materials, University of Louisiana at Lafayette, Madison Hall Room 217, P.O. Box 44130, Lafayette, LA 70504-1430 (United States); Zhang, Z.; Venkatasurya, P.K.C. [Center for Structural and Functional Materials, University of Louisiana at Lafayette, Madison Hall Room 217, P.O. Box 44130, Lafayette, LA 70504-1430 (United States); Somani, M.C.; Karjalainen, L.P. [Department of Mechanical Engineering, University of Oulu, P.O. Box 4200, Oulu 90014 (Finland)

2010-11-15

Research highlights: {yields} Development of a novel process involving phase-reversion annealing process. {yields} Austensite stability strongly influences development of nanograined structure. {yields} Interstitial elements influence microstructural evolution during annealing. - Abstract: We describe here an electron microscopy study of microstructural evolution associated with martensitic shear phase reversion-induced nanograined/ultrafine-grained (NG/UFG) structure in an experimental Fe-16Cr-10Ni alloy with very low interstitial content. The primary objective is to understand and obtain fundamental insights on the influence of degree of austenite stability (Fe-16Cr-10Ni, 301LN, and 301 have different austenite stability index) and interstitial elements (carbon and nitrogen) in terms of phase reversion process, microstructural evolution during reversion annealing, and temperature-time annealing sequence. A relative comparison of Fe-16Cr-10Ni alloy with 301LN and 301 austenitic stainless steels indicated that phase reversion in Fe-16Cr-10Ni occurred by shear mechanism, which is similar to that observed for 301, but is different from the diffusional mechanism in 301LN steel. While the phase reversion in the experimental Fe-16Cr-10Ni alloy and 301 austenitic stainless steel occurred by shear mechanism, there were fundamental differences between these two alloys. The reversed strain-free austenite grains in Fe-16Cr-10Ni alloy were characterized by nearly same crystallographic orientation, where as in 301 steel there was evidence of break-up of martensite laths during reversion annealing resulting in several regions of misoriented austenite grains in 301 steel. Furthermore, a higher phase reversion annealing temperature range (800-900 deg. C) was required to obtain a fully NG/UFG structure of grain size 200-600 nm. The difference in the phase reversion and the temperature-time sequence in the three stages is explained in terms of Gibbs free energy change that

Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice.

Science.gov (United States)

Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

2016-07-11

Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

Science.gov (United States)

Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Magnetic reversal spurts: Rain gauges for comet showers

International Nuclear Information System (INIS)

Lutz, T.M.

1988-01-01

Abrupt increases in the rate of magnetic reversals (magnetic reversal spurts) were first studied by many others. They hypothesized that spurts result from increased turbulence in the earth's core dynamo during episodes of intense bolide bombardment of the earth. Mechanisms for creating episodes of intense bombardment of the earth involve gravitational perturbation of the Oort cloud of comets, either by a hidden planet, a solar companion, or massive matter in the galactic plane. Herein, the time variation in reversal rate is analyzed using methods of statistical density estimation. A smooth, continuous estimate of reversal rate is obtained using an adaptive kernel method, in which the kernel width is adjusted as a function of reversal rate. The estimates near the ends of the data series (at 165 my ago and the present) are obtained by extending the data by reflection. The results show that the reversal spurts are not associated demonstrably with extinctions or well-dated impacts. If the spurts do record episodes of intense bombardment of the earth, then the mass extinctions do not, in general, occur at times of impacts. Furthermore, the large impact craters seen are not obviously related to the spurts, suggesting that the craters may have been caused by bolides of a different nature and with a different temporal pattern. However, the most simple explanation seems to be that the spurts do not record comet showers, either because the recording mechanism suggested by Muller and Morris is not effective or because comet showers are not triggered in the ways considered by Hut et al

Reversible flowchart languages and the structured reversible program theorem

DEFF Research Database (Denmark)

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

2008-01-01

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

Light-induced reversible expansion of individual gold nanoplates

Directory of Open Access Journals (Sweden)

Jinsheng Lu

2017-10-01

Full Text Available Light-induced mechanical response of materials has been extensively investigated and widely utilized to convert light energy into mechanical energy directly. The metallic nanomaterials have excellent photothermal properties and show enormous potential in micromechanical actuators, etc. However, the photo-thermo-mechanical properties of individual metallic nanostructures have yet to be well investigated. Here, we experimentally demonstrate a way to realize light-induced reversible expansion of individual gold nanoplates on optical microfibers. The light-induced thermal expansion coefficient is obtained as 21.4 ± 4.6 ∼ 31.5 ± 4.2 μ·K-1 when the light-induced heating temperature of the gold nanoplates is 240 ∼ 490 °C. The photo-thermo-mechanical response time of the gold nanoplates is about 0.3 ± 0.1 s. This insight into the photo-thermo-mechanical properties of the gold nanoplates could deepen the understanding of the light-induced reversible expansion behavior in nanoscale and pave the way for applications based on this piezoelectric-like response, such as light-driven metallic micromotors.

Reverse blocking characteristics and mechanisms in Schottky-drain AlGaN/GaN HEMT with a drain field plate and floating field plates

Science.gov (United States)

Wei, Mao; Wei-Bo, She; Cui, Yang; Jin-Feng, Zhang; Xue-Feng, Zheng; Chong, Wang; Yue, Hao

2016-01-01

In this paper, a novel AlGaN/GaN HEMT with a Schottky drain and a compound field plate (SD-CFP HEMT) is presented for the purpose of better reverse blocking capability. The compound field plate (CFP) consists of a drain field plate (DFP) and several floating field plates (FFPs). The physical mechanisms of the CFP to improve the reverse breakdown voltage and to modulate the distributions of channel electric field and potential are investigated by two-dimensional numerical simulations with Silvaco-ATLAS. Compared with the HEMT with a Schottky drain (SD HEMT) and the HEMT with a Schottky drain and a DFP (SD-FP HEMT), the superiorities of SD-CFP HEMT lie in the continuous improvement of the reverse breakdown voltage by increasing the number of FFPs and in the same fabrication procedure as the SD-FP HEMT. Two useful optimization laws for the SD-CFP HEMTs are found and extracted from simulation results. The relationship between the number of the FFPs and the reverse breakdown voltage as well as the FP efficiency in SD-CFP HEMTs are discussed. The results in this paper demonstrate a great potential of CFP for enhancing the reverse blocking ability in AlGaN/GaN HEMT and may be of great value and significance in the design and actual manufacture of SD-CFP HEMTs. Project supported by the National Natural Science Foundation of China (Grant Nos. 61204085, 61334002, 61306017, 61474091, 61574112, and 61574110).

Mechanism of Thermal Reversal of the (Fulvalene)tetracarbonyldiruthenium Photoisomerization: Toward Molecular Solar-Thermal Energy Storage

Energy Technology Data Exchange (ETDEWEB)

Kanai, Y; Srinivasan, V; Meier, S K; Vollhardt, K P; Grossman, J C

2010-02-18

In the currently intensifying quest to harness solar energy for the powering of our planet, most efforts are centered around photoinduced generic charge separation, such as in photovoltaics, water splitting, other small molecule activation, and biologically inspired photosynthetic systems. In contrast, direct collection of heat from sunlight has received much less diversified attention, its bulk devoted to the development of concentrating solar thermal power plants, in which mirrors are used to focus the sun beam on an appropriate heat transfer material. An attractive alternative strategy would be to trap solar energy in the form of chemical bonds, ideally through the photoconversion of a suitable molecule to a higher energy isomer, which, in turn, would release the stored energy by thermal reversal. Such a system would encompass the essential elements of a rechargeable heat battery, with its inherent advantages of storage, transportability, and use on demand. The underlying concept has been explored extensively with organic molecules (such as the norbornadiene-quadricyclane cycle), often in the context of developing photoswitches. On the other hand, organometallic complexes have remained relatively obscure in this capacity, despite a number of advantages, including expanded structural tunability and generally favorable electronic absorption regimes. A highly promising organometallic system is the previously reported, robust photo-thermal fulvalene (Fv) diruthenium couple 1 {l_reversible} 2 (Scheme 1). However, although reversible and moderately efficient, lack of a full, detailed atom-scale understanding of its key conversion and storage mechanisms have limited our ability to improve on its performance or identify optimal variants, such as substituents on the Fv, ligands other than CO, and alternative metals. Here we present a theoretical investigation, in conjunction with corroborating experiments, of the mechanism for the heat releasing step of 2 {yields} 1 and

Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.

Science.gov (United States)

Shibuta, Kazuo; Suzuki, Ikuko; Shinoda, Masamichi; Tsuboi, Yoshiyuki; Honda, Kuniya; Shimizu, Noriyoshi; Sessle, Barry J; Iwata, Koichi

2012-04-27

The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves. Copyright © 2012 Elsevier B.V. All rights reserved.

Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

Directory of Open Access Journals (Sweden)

Shota Yamamoto

2015-09-01

Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

Reverse Algols

Science.gov (United States)

Leung, K. C.

1989-01-01

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

I2 basal stacking fault as a degradation mechanism in reverse gate-biased AlGaN/GaN HEMTs

Science.gov (United States)

Lang, A. C.; Hart, J. L.; Wen, J. G.; Miller, D. J.; Meyer, D. J.; Taheri, M. L.

2016-09-01

Here, we present the observation of a bias-induced, degradation-enhancing defect process in plasma-assisted molecular beam epitaxy grown reverse gate-biased AlGaN/GaN high electron mobility transistors (HEMTs), which is compatible with the current theoretical framework of HEMT degradation. Specifically, we utilize both conventional transmission electron microscopy and aberration-corrected transmission electron microscopy to analyze microstructural changes in not only high strained regions in degraded AlGaN/GaN HEMTs but also the extended gate-drain access region. We find a complex defect structure containing an I2 basal stacking fault and offer a potential mechanism for device degradation based on this defect structure. This work supports the reality of multiple failure mechanisms during device operation and identifies a defect potentially involved with device degradation.

Event-related potential responses to perceptual reversals are modulated by working memory load.

Science.gov (United States)

Intaitė, Monika; Koivisto, Mika; Castelo-Branco, Miguel

2014-04-01

While viewing ambiguous figures, such as the Necker cube, the available perceptual interpretations alternate with one another. The role of higher level mechanisms in such reversals remains unclear. We tested whether perceptual reversals of discontinuously presented Necker cube pairs depend on working memory resources by manipulating cognitive load while recording event-related potentials (ERPs). The ERPs showed early enhancements of negativity, which were obtained in response to the first cube approximately 500 ms before perceived reversals. We found that working memory load influenced reversal-related brain responses in response to the second cube over occipital areas at the 150-300 ms post-stimulus and over central areas at P3 time window (300-500 ms), suggesting that it modulates intermediate visual processes. Interestingly, reversal rates remained unchanged by the working memory load. We propose that perceptual reversals in discontinuous presentation of ambiguous stimuli are governed by an early (well preceding pending reversals) mechanism, while the effects of load on the reversal related ERPs may reflect general top-down influences on visual processing, possibly mediated by the prefrontal cortex. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reverse Cholesterol Transport: Molecular Mechanisms and the Non-medical Approach to Enhance HDL Cholesterol

Directory of Open Access Journals (Sweden)

Leandro R. Marques

2018-05-01

Full Text Available Dyslipidemia (high concentrations of LDL-c and low concentrations of HDL-c is a major cause of cardiovascular events, which are the leading cause of death in the world. On the other hand, nutrition and regular exercise can be an interesting strategy to modulate lipid profile, acting as prevention or treatment, inhibiting the risk of diseases due to its anti-inflammatory and anti-atherogenic characteristics. Additionally, the possibility of controlling different training variables, such as type, intensity and recovery interval, can be used to maximize the benefits of exercise in promoting cardiovascular health. However, the mechanisms by which exercise and nutrients act in the regulation of cholesterol and its fractions, such as reverse cholesterol transport, receptors and transcription factors involved, such as PPARs and their role related to exercise, deserve further discussion. Therefore, the objective of this review is to debate about non-medical approaches to increase HDL-c, such as nutritional and training strategies, and to discuss the central mechanisms involved in the modulation of lipid profile during exercise, as well as that can be controlled by physical trainers or sports specialists in attempt to maximize the benefits promoted by exercise. The search for papers was performed in the databases: Medline (Pubmed, Science Direct, Scopus, Sport Discus, Web of Science, Scielo and Lilacs until February 2016.

Suppression of Pax2 attenuates allodynia and hyperalgesia through ET-1-ETAR-NFAT5 signaling in a rat model of neuropathic pain.

Science.gov (United States)

Tai, Lydia Wai; Pan, Zhiqiang; Sun, Liting; Li, Haobo; Gu, Pan; Wong, Stanley Sau Ching; Chung, Sookja K; Cheung, Chi Wai

2018-05-27

Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1-ETAR-NFAT5 is a novel regulatory mechanism underlying neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Elucidating the mechanism of posterior reversible encephalopathy syndrome: a case of transient blindness after central venous catheterization.

Science.gov (United States)

Rao, Neal M; Raychev, Radoslav; Kim, Doojin; Liebeskind, David S

2012-11-01

Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible symptoms including headache, visual disturbances, focal neurological deficits, altered mentation, and seizures. It has been associated with circumstances that may affect the cerebrovascular system, such as hypertension, eclampsia, and immunosuppression with calcineurin inhibitors. The underlying etiology of PRES has remained unclear; however, cerebrovascular autoregulatory dysfunction, hyperperfusion, and endothelial activation have been implicated. We describe a case of a young patient with lung transplant, who presented with headache, acute binocular blindness, and seizure immediately after infusion of saline through a peripherally inserted central catheter line, which inadvertently terminated cephalad in the left internal jugular vein, near the jugular foramen. Subsequent brain magnetic resonance imaging revealed vasogenic edematous lesions in a pattern consistent with PRES--a diagnosis supported by his constellation of symptoms, history of lung transplantation on tacrolimus immunosuppression, and relative hypertension. This is the first reported case describing the development of PRES after the insertion of a peripherally inserted central catheter line. The development of PRES in a typical high-risk patient immediately after cerebral venous outflow obstruction implicates the role of the cerebral venous system and provides potential insight into the mechanism of this disorder that remains of unclear pathogenesis.

CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

DEFF Research Database (Denmark)

Rosendahl, A; Kasch, Helge

Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

Time in Science: Reversibility vs. Irreversibility

Science.gov (United States)

Pomeau, Yves

To discuss properly the question of irreversibility one needs to make a careful distinction between reversibility of the equations of motion and the choice of the initial conditions. This is also relevant for the rather confuse philosophy of the wave packet reduction in quantum mechanics. The explanation of this reduction requires also to make precise assumptions on what initial data are accessible in our world. Finally I discuss how a given (and long) time record can be shown in an objective way to record an irreversible or reversible process. Or: can a direction of time be derived from its analysis? This leads quite naturally to examine if there is a possible spontaneous breaking of the time reversal symmetry in many body systems, a symmetry breaking that would be put in evidence objectively by looking at certain specific time correlations.

Gibbs Free Energy of Hydrolytic Water Molecule in Acyl-Enzyme Intermediates of a Serine Protease: A Potential Application for Computer-Aided Discovery of Mechanism-Based Reversible Covalent Inhibitors.

Science.gov (United States)

Masuda, Yosuke; Yamaotsu, Noriyuki; Hirono, Shuichi

2017-01-01

In order to predict the potencies of mechanism-based reversible covalent inhibitors, the relationships between calculated Gibbs free energy of hydrolytic water molecule in acyl-trypsin intermediates and experimentally measured catalytic rate constants (k cat ) were investigated. After obtaining representative solution structures by molecular dynamics (MD) simulations, hydration thermodynamics analyses using WaterMap™ were conducted. Consequently, we found for the first time that when Gibbs free energy of the hydrolytic water molecule was lower, logarithms of k cat were also lower. The hydrolytic water molecule with favorable Gibbs free energy may hydrolyze acylated serine slowly. Gibbs free energy of hydrolytic water molecule might be a useful descriptor for computer-aided discovery of mechanism-based reversible covalent inhibitors of hydrolytic enzymes.

Dynamic evolution and biogenesis of small RNAs during sex reversal.

Science.gov (United States)

Liu, Jie; Luo, Majing; Sheng, Yue; Hong, Qiang; Cheng, Hanhua; Zhou, Rongjia

2015-05-06

Understanding origin, evolution and functions of small RNA (sRNA) genes has been a great challenge in the past decade. Molecular mechanisms underlying sexual reversal in vertebrates, particularly sRNAs involved in this process, are largely unknown. By deep-sequencing of small RNA transcriptomes in combination with genomic analysis, we identified a large amount of piRNAs and miRNAs including over 1,000 novel miRNAs, which were differentially expressed during gonad reversal from ovary to testis via ovotesis. Biogenesis and expressions of miRNAs were dynamically changed during the reversal. Notably, phylogenetic analysis revealed dynamic expansions of miRNAs in vertebrates and an evolutionary trajectory of conserved miR-17-92 cluster in the Eukarya. We showed that the miR-17-92 cluster in vertebrates was generated through multiple duplications from ancestor miR-92 in invertebrates Tetranychus urticae and Daphnia pulex from the Chelicerata around 580 Mya. Moreover, we identified the sexual regulator Dmrt1 as a direct target of the members miR-19a and -19b in the cluster. These data suggested dynamic biogenesis and expressions of small RNAs during sex reversal and revealed multiple expansions and evolutionary trajectory of miRNAs from invertebrates to vertebrates, which implicate small RNAs in sexual reversal and provide new insight into evolutionary and molecular mechanisms underlying sexual reversal.

Neutrophil Reverse Migration Becomes Transparent with Zebrafish

Directory of Open Access Journals (Sweden)

Taylor W. Starnes

2012-01-01

Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

Reversible Carnot cycle outside a black hole

International Nuclear Information System (INIS)

Xi-Hao, Deng; Si-Jie, Gao

2009-01-01

A Carnot cycle outside a Schwarzschild black hole is investigated in detail. We propose a reversible Carnot cycle with a black hole being the cold reservoir. In our model, a Carnot engine operates between a hot reservoir with temperature T 1 and a black hole with Hawking temperature T H . By naturally extending the ordinary Carnot cycle to the black hole system, we show that the thermal efficiency for a reversible process can reach the maximal efficiency 1 – T H /T 1 . Consequently, black holes can be used to determine the thermodynamic temperature by means of the Carnot cycle. The role of the atmosphere around the black hole is discussed. We show that the thermal atmosphere provides a necessary mechanism to make the process reversible. (general)

Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats

Directory of Open Access Journals (Sweden)

Karina Genaro

2017-06-01

Full Text Available Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD, a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection.Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg. Conditioned place preference (CPP paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 μL injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 μL did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness.Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a

Managing Reverse Logistics or Reversing Logistics Management?

OpenAIRE

Brito, Marisa

2004-01-01

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

Magnetic reversal processes and critical thickness in FePt/α-Fe/FePt trilayers

International Nuclear Information System (INIS)

Guo, N.L.; Zhao, G.P.; Zhang, H.W.; Zhou, X.L.; Deng, Y.

2011-01-01

Magnetic reversal processes of a FePt/α-Fe/FePt trilayer system with in-plane easy axes have been investigated within a micromagnetic approach. It is found that the magnetic reversal process consists of three steps: nucleation of a prototype of domain wall in the soft phase, the evolution as well as the motion of the domain wall from the soft to the hard phase and finally, the magnetic reversal of the hard phase. For small soft layer thickness L s , the three steps are reduced to one single step, where the magnetizations in the two phases reverses simultaneously and the hysteresis loops are square with nucleation as the coercivity mechanism. As L s increases, both nucleation and pinning fields decrease. In the meantime, the single-step reversal expands to a standard three-step one and the coercivity mechanism changes from nucleation to pinning. The critical thickness where the coercivity mechanism alters, could be derived analytically, which is found to be inversely proportional to the square root of the crystalline anisotropy of the hard phase. Such a scaling law might provide an easy way to test the present theory. Further increase of L s leads to the change of the coercivity mechanism from pinning to nucleation. - Highlights: → Analytical critical thickness scales with square root of anisotropy of hard phase. → Reversal process determined nucleation, motion and depinning of domain walls. → Coercivity mechanism is nucleation and pinning for thin and thick soft layers. → Microscopic and macroscopic hysteresis loops calculated.

Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent)

International Nuclear Information System (INIS)

Zhu Aizhi; Wang Xiangyun; Guo Zhenquan

2001-01-01

The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99m Tc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99m Tc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99m Tc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 μg/ml of tea polyphenol respectively. The uptake of 99m Tc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 μM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment

Temperature dependent polarization reversal mechanism in 0.94(Bi1/2Na1/2) TiO3-0.06Ba(Zr0.02Ti0.98)O3 relaxor ceramics

DEFF Research Database (Denmark)

Glaum, Julia; Simons, Hugh; Hudspeth, Jessica

2015-01-01

and structural investigation of the polarization reversal process in the prototypical lead-free relaxor 0.94(Bi1/2Na1/2)TiO3-0.06Ba(Zr0.02Ti0.98)O3 reveals that an applied electric field can trigger depolarization and onset of relaxor-like behavior well below TF-R. The polarization reversal process can...... as such be described as a combination of (1) ferroelectric domain switching and (2) a reversible phase transition between two polar ferroelectric states mediated by a non-polar relaxor state. Furthermore, the threshold fields of the second, mediated polarization reversal mechanism depend strongly on temperature....... These results are concomitant with a continuous ferroelectric to relaxortransition occurring over a broad temperature range, during which mixed behavior is observed. The nature of polarization reversal can be illustrated in electric-field-temperature (E-T) diagrams showing the electric field amplitudes...

Parity- and time-reversal-violating moments of light nuclei

Energy Technology Data Exchange (ETDEWEB)

Vries, Jordy de, E-mail: devries@kvi.nl [KVI, theory group (Netherlands)

2013-03-15

I present the calculation of parity- and time-reversal-violating moments of the nucleon and light nuclei, originating from the QCD {theta}-bar term and effective dimension-six operators. By applying chiral effective field theory these calculations are performed in a unified framework. I argue that measurements of a few light-nuclear electric dipole moments would shed light on the mechanism of parity and time-reversal violation.

Charge reversal at a planar boundary between two dielectrics

Science.gov (United States)

Wang, Zhi-Yong

2016-01-01

Despite the ubiquitous character and relevance of the electric double layer in the entire realm of interface and colloid science, very little is known of the effect that surface heterogeneity exerts on the underlying mechanisms of ion adsorption. Herein, computer simulations offer a perspective that, in sharp contrast to the homogeneously charged surface, discrete groups promote multivalent counterion binding, leading to charge reversal but possibly having not a sign change of the electrophoretic mobility. Counterintuitively, the introduction of dielectric images yields a significantly greater accumulation of counterions, which further facilitates the magnitude of charge reversal. The reported results are very sensitive to both the degree of ion hydration and the representation of surface charges. Our findings shed light on the mechanism for charge reversal over a broad range of coupling regimes operating the adsorption of counterions through surface group bridging attraction with their own images and provide opportunities for experimental studies and theoretical development.

Reversibly Bistable Flexible Electronics

KAUST Repository

Alfaraj, Nasir

2015-05-01

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

Thermally activated magnetization reversal in magnetic tunnel junctions

International Nuclear Information System (INIS)

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

2009-01-01

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

Reverse Logistics

OpenAIRE

Kulikova, Olga

2016-01-01

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

Spinal CPEB-mtROS-CBP signaling pathway contributes to perineural HIV gp120 with ddC-related neuropathic pain in rats.

Science.gov (United States)

Iida, Takafumi; Yi, Hyun; Liu, Shue; Huang, Wan; Kanda, Hirotsugu; Lubarsky, David A; Hao, Shuanglin

2016-07-01

Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously received them, and many have developed painful peripheral neuropathy. The exact mechanisms by which HIV with NRTIs contribute to the development of neuropathic pain are not known. Previous studies suggest that cytoplasmic polyadenylation element-binding protein (CPEB), reactive oxygen species (ROS), and cAMP-response element-binding protein (CREB)-binding protein (CBP), are involved in the neuroimmunological diseases including inflammatory/neuropathic pain. In this study, we investigated the role of CPEB, mitochondrial ROS (mtROS), or CBP in neuropathic pain induced by HIV envelope protein gp120 combined with antiretroviral drug. The application of recombinant gp120 into the sciatic nerve plus systemic ddC (one of NRTIs) induced mechanical allodynia. Knockdown of CPEB or CBP using intrathecal antisense oligodeoxynucleotide (AS-ODN) reduced mechanical allodynia. Intrathecal mitochondrial superoxide scavenger mito-tempol (Mito-T) increased mechanical withdrawal threshold. Knockdown of CPEB using intrathecal AS-ODN, reduced the up-regulated mitochondrial superoxide in the spinal dorsal horn in rats with gp120 combined with ddC. Intrathecal Mito-T lowered the increased expression of CBP in the spinal dorsal horn. Immunostaining studies showed that neuronal CPEB positive cells were co-localized with MitoSox positive profiles, and that MitoSox positive profiles were co-localized with neuronal CBP. Our studies suggest that neuronal CPEB-mtROS-CBP pathway in the spinal dorsal horn, plays an important role in the gp120/ddC-induced neuropathic pain in rats. Copyright © 2016. Published by Elsevier Inc.

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

Directory of Open Access Journals (Sweden)

Su Lin

2011-11-01

Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

Reversible aqueous zinc/manganese oxide energy storage from conversion reactions

Energy Technology Data Exchange (ETDEWEB)

Pan, Huilin; Shao, Yuyan; Yan, Pengfei; Cheng, Yingwen; Han, Kee Sung; Nie, Zimin; Wang, Chongmin; Yang, Jihui; Li, Xiaolin; Bhattacharya, Priyanka; Mueller, Karl T.; Liu, Jun

2016-04-18

Rechargeable aqueous batteries are attracting growing interest for energy storage due to their low cost and high safety. Fundamental understanding of highly reversible aqueous reactions is critical for building high-performance batteries. Herein, we studied the reversibility of Zn/MnO2 battery chemistry in mild aqueous MnSO4 electrolytes. α-MnO2 nanofibers were used as a high performance cathode. Our study provides good evidence for a conversion reaction mechanism through reversible formation of short nanorods and nanoparticle aggregates. This reversible conversion reaction provides an operating voltage of 1.44 V, high capacity of 285 mAh g-1, excellent rate and capacity retention of 92% after 5000 cycles. Zn metal anode also shows high reversibility in the mild aqueous MnSO4 electrolytes. The highly reversible and stable chemistries in aqueous Zn/MnO2 batteries open new opportunity for energy storage technologies with potentially high energy density, high safety, and low cost.

Preventive Effects of Bee Venom Derived Phospholipase A₂ on Oxaliplatin-Induced Neuropathic Pain in Mice.

Science.gov (United States)

Li, Dongxing; Kim, Woojin; Shin, Dasom; Jung, Yongjae; Bae, Hyunsu; Kim, Sun Kwang

2016-01-19

Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A₂ (bvPLA₂) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7-9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA₂ (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA₂ were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA₂ may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs.

Reversion of hyperhydricity in pink (Dianthus chinensis L.) plantlets by AgNO3 and its associated mechanism during in vitro culture.

Science.gov (United States)

Gao, Hongyang; Xia, Xiuying; An, Lijia; Xin, Xin; Liang, Yuan

2017-01-01

Hyperhydricity occurs frequently in plant tissue culture and can severely affect commercial micropropagation and genetic improvement of the cultured plantlets. Hyperhydric shoots are charaterzized by high water content, but how this occurs is still a subject of investigation. Silver ion (Ag + ) can reduce the extent of hyperhydricity in plants, but its effect on the reversion of hyperhydric plantlets and the underlying mechanism of reversion has not been clarified. In this study, about 67% of the hyperhydric Dianthus chinensis L. plantlets were found to revert to normal condition when the plantlets were cultured in medium supplemented with 29.4μmolL -1 AgNO 3 . Water content and hydrogen peroxide (H 2 O 2 ) content in the guard cells of these plantlets were reduced, while stomatal aperture and water loss rate were increased. AgNO 3 also reduced the content of endogenous ethylene and expression of ethylene synthesis and ethylene signal transduction-associated genes. Reduced accumulation of ethylene consequently led to an increase in stomatal aperture mediated by decreased H 2 O 2 content in the guard cells. These results adequately verified the role of AgNO 3 in the reversion of hyperhydricity in D. chinensis L. and also provided clues for exploring the cause of excessive water accumulation in hyperhydric plants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain.

Science.gov (United States)

Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

2015-01-01

We aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.

Sleep Deprivation and Recovery Sleep Prior to a Noxious Inflammatory Insult Influence Characteristics and Duration of Pain.

Science.gov (United States)

Vanini, Giancarlo

2016-01-01

Insufficient sleep and chronic pain are public health epidemics. Sleep loss worsens pain and predicts the development of chronic pain. Whether previous, acute sleep loss and recovery sleep determine pain levels and duration remains poorly understood. This study tested whether acute sleep deprivation and recovery sleep prior to formalin injection alter post-injection pain levels and duration. Male Sprague-Dawley rats (n = 48) underwent sleep deprivation or ad libitum sleep for 9 hours. Thereafter, rats received a subcutaneous injection of formalin or saline into a hind paw. In the recovery sleep group, rats were allowed 24 h between sleep deprivation and the injection of formalin. Mechanical and thermal nociception were assessed using the von Frey test and Hargreaves' method. Nociceptive measures were performed at 1, 3, 7, 10, 14, 17 and 21 days post-injection. Formalin caused bilateral mechanical hypersensitivity (allodynia) that persisted for up to 21 days post-injection. Sleep deprivation significantly enhanced bilateral allodynia. There was a synergistic interaction when sleep deprivation preceded a formalin injection. Rats allowed a recovery sleep period prior to formalin injection developed allodynia only in the injected limb, with higher mechanical thresholds (less allodynia) and a shorter recovery period. There were no persistent changes in thermal nociception. The data suggest that acute sleep loss preceding an inflammatory insult enhances pain and can contribute to chronic pain. The results encourage studies in a model of surgical pain to test whether enhancing sleep reduces pain levels and duration. © 2016 Associated Professional Sleep Societies, LLC.

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia.

Science.gov (United States)

López-Granero, Caridad; Antunes Dos Santos, Alessandra; Ferrer, Beatriz; Culbreth, Megan; Chakraborty, Sudipta; Barrasa, Angel; Gulinello, Maria; Bowman, Aaron B; Aschner, Michael

2017-06-01

Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers. Specifically, we assessed social preference, elevated plus maze, forced swim, and Von Frey tests at 3-4 months-of-age, as well as activation of cytokines and antioxidant mRNA levels in the cortex at 7 months-of-age. We report that (1) the BXD84/RwwJ RI strain exhibits anxiety disorder and social avoidance-like behavior (2) BXD21/TyJ RI strain shows a resistance to depression illness, and (3) sex-dependent cytokine profiles and allodynia with elevated inflammatory activity were inherent to male BXD21/TyJ RI mice. In conclusion, we provide novel data in favor of the use of BXD recombinant inbred mice to further understand anxiety and depression disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on the coherence degree of magnetization reversal in Permalloy single-domain nano-ellipses

Energy Technology Data Exchange (ETDEWEB)

Júnior, D.S. Vieira [Departamento Acadêmico de Matemática, Física, e Estatística, Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais – Campus Rio Pomba, Rio Pomba, Minas Gerais 36180-000 (Brazil); Leonel, S.A. [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil); Toscano, D., E-mail: danilotoscano@fisica.ufjf.br [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil); Sato, F.; Coura, P.Z.; Dias, R.A. [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil)

2017-03-15

Numerical simulations have been performed to study the magnetization reversal in Permalloy nano-ellipses, under combined in-plane magnetic fields along the longitudinal and the transverse directions. We have considered nano-ellipses with two different aspect ratios and five thicknesses: 220×80×t nm{sup 3} and 70×50×t nm{sup 3}, where t ranging from 5 to 25 nm in steps of 5 nm. We found that the mechanism of magnetization reversal is not only dependent on the parameters of the magnetic field pulse but also related to the ellipse dimensions. It is known that the reversal time is related to the mechanism behind the magnetization reversal. In particular, ultrafast magnetization reversals occur by coherent rotation, when applying a field oriented mainly perpendicular to the initial magnetization. In order to evaluate the degree of coherence of the magnetization reversal we have introduced a quantity called “coherence index”. Besides complementing the previous studies by including the effect of the thickness on the magnetization reversal, our results indicate that it is possible to obtain magnetization reversals with high degree of coherence in small nano-ellipses by adjusting the geometric factors of the ellipse and the parameters of the magnetic field pulse simultaneously. - Highlights: • Magnetization reversals in single-domain nano-ellipses were investigated. • A parameter to evaluate the degree of coherence of the magnetization reversal was proposed. • A higher coherence index indicates a complete, coherent, rotation of the magnetization.

Origin of reverse annealing effect in hydrogen-implanted silicon

Energy Technology Data Exchange (ETDEWEB)

Di, Zengfeng [Los Alamos National Laboratory; Nastasi, Michael A [Los Alamos National Laboratory; Wang, Yongqiang [Los Alamos National Laboratory

2009-01-01

In contradiction to conventional damage annealing, thermally annealed H-implanted Si exhibits an increase in damage or reverse annealing behavior, whose mechanism has remained elusive. On the basis of quantitative high resolution transmission electron microscopy combined with channeling Rutherford backscattering analysis, we conclusively elucidate that the reverse annealing effect is due to the nucleation and growth of hydrogen-induce platelets. Platelets are responsible for an increase in the height and width the channeling damage peak following increased isochronal anneals.

Monoamines stimulate sex reversal in the saddleback wrasse.

Science.gov (United States)

Larson, Earl T; Norris, David O; Gordon Grau, E; Summers, Cliff H

2003-02-15

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a

Ropivacaine and Bupivacaine prevent increased pain sensitivity without altering neuroimmune activation following repeated social defeat stress.

Science.gov (United States)

Sawicki, Caroline M; Kim, January K; Weber, Michael D; Jarrett, Brant L; Godbout, Jonathan P; Sheridan, John F; Humeidan, Michelle

2018-03-01

Mounting evidence indicates that stress influences the experience of pain. Exposure to psychosocial stress disrupts bi-directional communication pathways between the central nervous system and peripheral immune system, and can exacerbate the frequency and severity of pain experienced by stressed subjects. Repeated social defeat (RSD) is a murine model of psychosocial stress that recapitulates the immune and behavioral responses to stress observed in humans, including activation of stress-reactive neurocircuitry and increased pro-inflammatory cytokine production. It is unclear, however, how these stress-induced neuroimmune responses contribute to increased pain sensitivity in mice exposed to RSD. Here we used a technique of regional analgesia with local anesthetics in mice to block the development of mechanical allodynia during RSD. We next investigated the degree to which pain blockade altered stress-induced neuroimmune activation and depressive-like behavior. Following development of a mouse model of regional analgesia with discrete sensory blockade over the dorsal-caudal aspect of the spine, C57BL/6 mice were divided into experimental groups and treated with Ropivacaine (0.08%), Liposomal Bupivacaine (0.08%), or Vehicle (0.9% NaCl) prior to exposure to stress. This specific region was selected for analgesia because it is the most frequent location for aggression-associated pain due to biting during RSD. Mechanical allodynia was assessed 12 h after the first, third, and sixth day of RSD after resolution of the sensory blockade. In a separate experiment, social avoidance behavior was determined after the sixth day of RSD. Blood, bone marrow, brain, and spinal cord were collected for immunological analyses after the last day of RSD in both experiments following behavioral assessments. RSD increased mechanical allodynia in an exposure-dependent manner that persisted for at least one week following cessation of the stressor. Mice treated with either Ropivacaine or

Spin-orbit torque induced magnetic vortex polarity reversal utilizing spin-Hall effect

Science.gov (United States)

Li, Cheng; Cai, Li; Liu, Baojun; Yang, Xiaokuo; Cui, Huanqing; Wang, Sen; Wei, Bo

2018-05-01

We propose an effective magnetic vortex polarity reversal scheme that makes use of spin-orbit torque introduced by spin-Hall effect in heavy-metal/ferromagnet multilayers structure, which can result in subnanosecond polarity reversal without endangering the structural stability. Micromagnetic simulations are performed to investigate the spin-Hall effect driven dynamics evolution of magnetic vortex. The mechanism of magnetic vortex polarity reversal is uncovered by a quantitative analysis of exchange energy density, magnetostatic energy density, and their total energy density. The simulation results indicate that the magnetic vortex polarity is reversed through the nucleation-annihilation process of topological vortex-antivortex pair. This scheme is an attractive option for ultra-fast magnetic vortex polarity reversal, which can be used as the guidelines for the choice of polarity reversal scheme in vortex-based random access memory.

Reversible Splenial Lesion Syndrome (RESLES) Following Glufosinate Ammonium Poisoning.

Science.gov (United States)

Jeong, Tae Oh; Yoon, Jae Chol; Lee, Jae Baek; Jin, Young Ho; Hwang, Seung Bae

2015-01-01

Isolated and reversible lesion restricted to the splenium of the corpus callosum, known as reversible splenial lesion syndrome, have been reported in patients with infection, high-altitude cerebral edema, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Here, we report a 39-year-old female patient with glufosinate ammonium (GLA) poisoning who presented with confusion and amnesia. Diffusion-weighted magnetic resonance imaging of the brain revealed cytotoxic edema of the splenium of the corpus callosum. The lesion was not present on follow-up MR imaging performed 9 months later. We postulate that a GLA-induced excitotoxic mechanism was the cause of this reversible splenial lesion. Copyright © 2015 by the American Society of Neuroimaging.

Botulinum toxin type A for cephalic cutaneous allodynia in chronic migraine: a randomized, double-blinded, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Luciano Hollanda

2014-12-01

Full Text Available Cephalic allodynia (CA can be observed in 50-70% of patients with chronic migraine (CM. The aim of this trial was to assess the efficacy of botulinum toxin type A (Botx-A in the treatment of CA associated with CM. In this placebo-controlled trial, patients were randomized either into Botx-A or 0.9% saline injections and efficacy measures were assessed every 4 weeks for 3 months. Efficacy endpoints were number of migraine episodes associated with CA, changes from baseline in visual analogical scale scores for pain (VAS and frequency of common analgesics use for migraine. A total of 38 subjects were randomized to saline (n=18 or Botx-A (n=20. There were no significant differences in baseline between active intervention or placebo groups regarding mean age, number of headache episodes [mean 12.1 (9.22 and 17.00 (9.69 respectively; P=0.12], pain severity as measured by the VAS or frequency of analgesic use for headache episodes. Efficacy analysis showed that Botx-A injections led to an important decrease from baseline in the mean migraine episodes associated with CA after 12 weeks (5.20 versus 11.17; P=0.01. Also, VAS scores and frequency of analgesics use for headache were significantly reduced in the Botx-A group. This study suggests that Botx-A injections are superior to saline in the treatment of CA associated with CM, with mild self limited side effects.

Reversible a-Fe2O3 to Fe3O4 transformation during ball milling

DEFF Research Database (Denmark)

Linderoth, Søren; Jiang, Jianzhong; Mørup, Steen

1997-01-01

The transformation of hematite to magnetite by high-energy ball milling in a sealed container has been studied by Mossbauer spectroscopy and x-ray diffraction. Mechanisms for this transformation are critically discussed. The dominant mechanism is concluded to be due to bond breaking during the high...... energy ball milling followed by release of the oxygen from the vial. The reverse transformation, magnetite to hematite, is demonstrated to occur by ball milling in air. Mechanisms for this reverse transformation are also put forward....

Inherited XX sex reversal originating from wild medaka populations.

Science.gov (United States)

Shinomiya, A; Otake, H; Hamaguchi, S; Sakaizumi, M

2010-11-01

The teleost fish, medaka (Oryzias latipes), has an XX/XY sex-determining mechanism. A Y-linked DM domain gene, DMY, has been isolated by positional cloning as the sex-determining gene in this species. Previously, we conducted a field survey of genotypic sex and found that approximately 1% of wild medaka are sex-reversed (XX males and XY females). Here, we performed genetic analyses of nine spontaneous XX sex-reversed males to elucidate its genetic basis. In all cases, the F(1) progeny were all females, whereas XX males reappeared in the backcross (BC) progeny, suggesting that XX sex reversal is a recessive trait. Although the incidences of sex reversal in the BC progeny were mostly low, 40% were males derived from one XX male. We performed linkage analysis using 55 BC males and located a single major factor, sda-1 (sex-determining autosomal factor-1), controlling sex reversal in an autosomal linkage group. Thus, genes involved in the sex-determining pathway can be isolated from spontaneous mutants in wild populations.

The GABAergic Anterior Paired Lateral Neurons Facilitate Olfactory Reversal Learning in "Drosophila"

Science.gov (United States)

Wu, Yanying; Ren, Qingzhong; Li, Hao; Guo, Aike

2012-01-01

Reversal learning has been widely used to probe the implementation of cognitive flexibility in the brain. Previous studies in monkeys identified an essential role of the orbitofrontal cortex (OFC) in reversal learning. However, the underlying circuits and molecular mechanisms are poorly understood. Here, we use the T-maze to investigate the neural…

TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

Science.gov (United States)

Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

2018-05-08

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

Reversible adaptive plasticity: A mechanism for neuroblastoma cell heterogeneity and chemo-resistance

Directory of Open Access Journals (Sweden)

Lina eChakrabarti

2012-08-01

Full Text Available We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD or sphere forming, anchorage independent (AI growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

Reversible Adaptive Plasticity: A Mechanism for Neuroblastoma Cell Heterogeneity and Chemo-Resistance

Energy Technology Data Exchange (ETDEWEB)

Chakrabarti, Lina; Abou-Antoun, Thamara; Vukmanovic, Stanislav; Sandler, Anthony D., E-mail: asandler@childrensnational.org [The Joseph E. Robert Center for Surgical Care, Children’s National Medical Center, Washington, DC (United States); The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Medical Center, Washington, DC (United States)

2012-08-02

We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD) or sphere forming, anchorage independent (AI) growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity, and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin, and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic, and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma.

Measurement of variable magnetic reversal paths in electrically contacted pseudo-spin-valve rings

International Nuclear Information System (INIS)

Hayward, T J; Llandro, J; Schackert, F D O; Morecroft, D; Balsod, R B; Bland, J A C; Castano, F J; Ross, C A

2007-01-01

In this work we show that the measurement of single magnetic reversal events is of critical importance in order to correctly characterize the switching of magnetic microstructures. Magnetoresistance measurements are performed on two pseudo-spin-valve ring structures with high enough signal to noise to allow the probing of single reversal events. Using this technique we acquire 'switching spectra' which demonstrate that the rings exhibit a range of variable reversal paths, including a bistable reversal mechanism of the hard layer, where the two switching routes have substantially different switching fields. The signature of the variable reversal paths would have been obscured in field cycle averaged data and in the bistable case would cause a fundamental misinterpretation of the reversal behaviour

Reversible Thermoset Adhesives

Science.gov (United States)

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

2016-01-01

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

Temperature dependent polarization reversal mechanism in 0.94(Bi1/2Na1/2)TiO3-0.06Ba(Zr0.02Ti0.98)O3 relaxor ceramics

Science.gov (United States)

Glaum, Julia; Simons, Hugh; Hudspeth, Jessica; Acosta, Matias; Daniels, John E.

2015-12-01

The temperature at which the electric field induced long-range ordered ferroelectric state undergoes transition into the short-range ordered relaxor state, TF-R, is commonly defined by the onset of strong dispersion of the dielectric permittivity. However, this combined macroscopic property and structural investigation of the polarization reversal process in the prototypical lead-free relaxor 0.94(Bi1/2Na1/2)TiO3-0.06Ba(Zr0.02Ti0.98)O3 reveals that an applied electric field can trigger depolarization and onset of relaxor-like behavior well below TF-R. The polarization reversal process can as such be described as a combination of (1) ferroelectric domain switching and (2) a reversible phase transition between two polar ferroelectric states mediated by a non-polar relaxor state. Furthermore, the threshold fields of the second, mediated polarization reversal mechanism depend strongly on temperature. These results are concomitant with a continuous ferroelectric to relaxor transition occurring over a broad temperature range, during which mixed behavior is observed. The nature of polarization reversal can be illustrated in electric-field-temperature (E-T) diagrams showing the electric field amplitudes associated with different polarization reversal processes. Such diagrams are useful tools for identifying the best operational temperature regimes for a given composition in actuator applications.

Zero field reversal probability in thermally assisted magnetization reversal

Science.gov (United States)

Prasetya, E. B.; Utari; Purnama, B.

2017-11-01

This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

Dynamical similarity of geomagnetic field reversals.

Science.gov (United States)

Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent; Herrero-Bervera, Emilio

2012-10-04

No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components. Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 180° polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments.

Analysis of Reverse-Bias Leakage Current Mechanisms in Metal/GaN Schottky Diodes

Directory of Open Access Journals (Sweden)

P. Pipinys

2010-01-01

Full Text Available Temperature-dependent reverse-bias current-voltage characteristics obtained by other researchers for Schottky diodes fabricated on GaN are reinterpreted in terms of phonon-assisted tunneling (PhAT model. Temperature dependence of reverse-bias leakage current is shown could be caused by the temperature dependence of electron tunneling rate from traps in the metal-semiconductor interface to the conduction band of semiconductor. A good fit of experimental data with the theory is received in a wide temperature range (from 80 K to 500 K using for calculation the effective mass of 0.222 me. and for the phonon energy the value of 70 meV. The temperature and bias voltages dependences of an apparent barrier height (activation energy are also explicable in the framework of the PhAT model.

Reversible temper brittleness on tensile tests at room temperature

International Nuclear Information System (INIS)

Quadros, N.F. de; Cabral, U.Q.

1976-01-01

Tensile tests were carried out on unnotched test pieces at room temperature and three strain rates: 2,5x10 -4 , 2,5x10 -3 and 1,0x10 -2 s -1 in a low alloy No-Cr-Mo steel to observe the variation in its mechanical properties with the occurrence of reversible temper brittleness. The brittle samples showed a sensitivity of 50 0 C in a 48 hour heat treatment at 500 0 C. The tests showed that at the strain rate of 2,5x10 -4 s -1 there are statistically significant differences between the elongations of the material in the brittle and the nonbrittle and regenerated states. A short review of reversible temper brittleness is given and a theory suggested for the mechanism [pt

Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

African Journals Online (AJOL)

NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan. Abstract. Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni.

Reverse Osmosis

Indian Academy of Sciences (India)

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

Acute versus chronic phase mechanisms in a rat model of CRPS.

Science.gov (United States)

Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism

Science.gov (United States)

Kim, Eunkyoung; Panzella, Lucia; Micillo, Raffaella; Bentley, William E.; Napolitano, Alessandra; Payne, Gregory F.

2015-01-01

Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin’s pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin’s redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism. PMID:26669666

Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

Directory of Open Access Journals (Sweden)

Carlton Susan M

2010-03-01

Full Text Available Abstract Background Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR, we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.

Early reversal cells in adult human bone remodeling

DEFF Research Database (Denmark)

Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

2016-01-01

The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter...... of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts....... Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...

Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury.

Science.gov (United States)

Nyland, Jennifer E; McLean, Samuel A; Averitt, Dayna L

2015-12-01

Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Poloidal flux loss in a field-reversed theta pinch

International Nuclear Information System (INIS)

Hoffman, A.L.; Milroy, R.D.; Steinhauer, L.C.

1981-01-01

Poloidal flux loss has been measured in field-reversed configurations and related to anomalous resistivity near the magnetic field null. The results indicate that mechanisms in addition to the lower-hybrid drift instability are affecting transport

Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.

Science.gov (United States)

Sun, Rao; Zhang, Zuoxia; Lei, Yishan; Liu, Yue; Lu, Cui'e; Rong, Hui; Sun, Yu'e; Zhang, Wei; Ma, Zhengliang; Gu, Xiaoping

2016-01-01

The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder. © The Author(s) 2016.

Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

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Kanako So

2015-03-01

Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

Molecular Hydrogen Attenuates Neuropathic Pain in Mice

Science.gov (United States)

Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

2014-01-01

Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

Epigenetic modification and inheritance in sexual reversal of fish.

Science.gov (United States)

Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

2014-04-01

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

Physics of reversed-field pinch profile sustainment

International Nuclear Information System (INIS)

Moses, R.W.

1984-01-01

A description of the Reversed-Field Pinch (RFP) is given, emphasizing the necessity of a magnetohydrodynamic (MHD) or kinetic process to sustain field reversal. Three sustainment mechanisms are reviewed: the MHD dynamo, the tangled discharge model, and nonlocal resistivity. A slab model of steady (ohmic) states is described. A relationship between ohmic state wave numbers and the minimum amplitude of nonsymmetric field components is given. If ohmic states are the sole source of the sustainment process, their wave lengths are probably much longer than the minor diameter of the plasma. Otherwise field asymmetries would exceed those observed in experiments. It is noted that internal field data are still limited, restricting the generality of our comments

Reversible brazing process

Science.gov (United States)

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

1999-01-01

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

Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia.

Science.gov (United States)

Montilla-García, Ángeles; Tejada, Miguel Á; Perazzoli, Gloria; Entrena, José M; Portillo-Salido, Enrique; Fernández-Segura, Eduardo; Cañizares, Francisco J; Cobos, Enrique J

2017-10-01

Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dynamic evolution and biogenesis of small RNAs during sex reversal

OpenAIRE

Liu, Jie; Luo, Majing; Sheng, Yue; Hong, Qiang; Cheng, Hanhua; Zhou, Rongjia

2015-01-01

Understanding origin, evolution and functions of small RNA (sRNA) genes has been a great challenge in the past decade. Molecular mechanisms underlying sexual reversal in vertebrates, particularly sRNAs involved in this process, are largely unknown. By deep-sequencing of small RNA transcriptomes in combination with genomic analysis, we identified a large amount of piRNAs and miRNAs including over 1,000 novel miRNAs, which were differentially expressed during gonad reversal from ovary to testis...

Inorganic fouling mitigation by salinity cycling in batch reverse osmosis

OpenAIRE

Maswadeh, Laith A.; Warsinger, David Elan Martin; Tow, Emily W.; Connors, Grace B.; Swaminathan, Jaichander; Lienhard, John H

2018-01-01

Enhanced fouling resistance has been observed in recent variants of reverse osmosis (RO) desalination which use time-varying batch or semi-batch processes, such as closed-circuit RO (CCRO) and pulse flow RO (PFRO). However, the mechanisms of batch processes' fouling resistance are not well-understood, and models have not been developed for prediction of their fouling performance. Here, a framework for predicting reverse osmosis fouling is developed by comparing the fluid residence time in bat...

Deciphering the molecular mechanisms underlying sea urchin reversible adhesion : A quantitative proteomics approach

NARCIS (Netherlands)

Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen|info:eu-repo/dai/nl/313939780; Cordeiro, Carlos; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Santos, Romana

2016-01-01

Marine bioadhesives have unmatched performances in wet environments, being an inspiration for biomedical applications. In sea urchins specialized adhesive organs, tube feet, mediate reversible adhesion, being composed by a disc, producing adhesive and de-adhesive secretions, and a motile stem. After

Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI.

Science.gov (United States)

Rudick, Charles N; Taylor, Aisha K; Yaggie, Ryan E; Schaeffer, Anthony J; Klumpp, David J

2014-01-01

Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.

The RNA binding protein HuR does not interact directly with HIV-1 reverse transcriptase and does not affect reverse transcription in vitro

Directory of Open Access Journals (Sweden)

Gronenborn Angela M

2010-05-01

Full Text Available Abstract Background Lemay et al recently reported that the RNA binding protein HuR directly interacts with the ribonuclease H (RNase H domain of HIV-1 reverse transcriptase (RT and influences the efficiency of viral reverse transcription (Lemay et al., 2008, Retrovirology 5:47. HuR is a member of the embryonic lethal abnormal vision protein family and contains 3 RNA recognition motifs (RRMs that bind AU-rich elements (AREs. To define the structural determinants of the HuR-RT interaction and to elucidate the mechanism(s by which HuR influences HIV-1 reverse transcription activity in vitro, we cloned and purified full-length HuR as well as three additional protein constructs that contained the N-terminal and internal RRMs, the internal and C-terminal RRMs, or the C-terminal RRM only. Results All four HuR proteins were purified and characterized by biophysical methods. They are well structured and exist as monomers in solution. No direct protein-protein interaction between HuR and HIV-1 RT was detected using NMR titrations with 15N labeled HuR variants or the 15N labeled RNase H domain of HIV-1 RT. Furthermore, HuR did not significantly affect the kinetics of HIV-1 reverse transcription in vitro, even on RNA templates that contain AREs. Conclusions Our results suggest that HuR does not impact HIV-1 replication through a direct protein-protein interaction with the viral RT.

Managing Reverse Logistics or Reversing Logistics Management?

NARCIS (Netherlands)

M.P. de Brito (Marisa)

2004-01-01

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

Stainless austenitic steels strengthened due to reversible phase transformations and by ageing

International Nuclear Information System (INIS)

Sagaradze, V.V.; Kositsyna, I.I.; Ozhiganov, A.V.

1981-01-01

The effect of the reversible phase transformations, consisting in the conduction of the direct and reverse martensite transformations and aging, during which the intermetallide γ'-phase of the composition Ni 3 Ti is formed, on the streng-thening of alloys in the Fe-Cr-Ni-Ti system is considered. Stainless austenitic steels Kh12N12T3 and Kh12N14T3, which acquire high mechanical properties: σsub(0.2)=685-785 MPa, σsub(B)=1275 MPa, delta >= 20%, as a result of reversible phase transformations and aging, are suggested. After the reversible phase transformations and ageing the steels possess a high resistance to γ-α-transformation during cold treatment [ru

Electrochemical transformation of trichloroethylene in aqueous solution by electrode polarity reversal.

Science.gov (United States)

Rajic, Ljiljana; Fallahpour, Noushin; Yuan, Songhu; Alshawabkeh, Akram N

2014-12-15

Electrode polarity reversal is evaluated for electrochemical transformation of trichloroethylene (TCE) in aqueous solution using flow-through reactors with mixed metal oxide electrodes and Pd catalyst. The study tests the hypothesis that optimizing electrode polarity reversal will generate H2O2 in Pd presence in the system. The effect of polarity reversal frequency, duration of the polarity reversal intervals, current intensity and TCE concentration on TCE removal rate and removal mechanism were evaluated. TCE removal efficiencies under 6 cycles h(-1) were similar in the presence of Pd catalyst (50.3%) and without Pd catalyst (49.8%), indicating that Pd has limited impact on TCE degradation under these conditions. The overall removal efficacies after 60 min treatment under polarity reversal frequencies of 6, 10, 15, 30 and 90 cycles h(-1) were 50.3%, 56.3%, 69.3%, 34.7% and 23.4%, respectively. Increasing the frequency of polarity reversal increases TCE removal as long as sufficient charge is produced during each cycle for the reaction at the electrode. Electrode polarity reversal shifts oxidation/reduction and reduction/oxidation sequences in the system. The optimized polarity reversal frequency (15 cycles h(-1) at 60 mA) enables two reaction zones formation where reduction/oxidation occurs at each electrode surface. Published by Elsevier Ltd.

"ALS reversals": demographics, disease characteristics, treatments, and co-morbidities.

Science.gov (United States)

Harrison, Daniel; Mehta, Paul; van Es, Michael A; Stommel, Elijah; Drory, Vivian E; Nefussy, Beatrice; van den Berg, Leonard H; Crayle, Jesse; Bedlack, Richard

2018-04-02

To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS. Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study.

Quinolone Resistance Reversion by Targeting the SOS Response.

Science.gov (United States)

Recacha, E; Machuca, J; Díaz de Alba, P; Ramos-Güelfo, M; Docobo-Pérez, F; Rodriguez-Beltrán, J; Blázquez, J; Pascual, A; Rodríguez-Martínez, J M

2017-10-10

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog 10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog 10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

Science.gov (United States)

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

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Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

Magnetization reversal in single molecule magnets

Science.gov (United States)

Bokacheva, Louisa

2002-09-01

I have studied the magnetization reversal in single molecule magnets (SMMs). SMMs are Van der Waals crystals, consisting of identical molecules containing transition metal ions, with high spin and large uniaxial magnetic anisotropy. They can be considered as ensembles of identical, iso-oriented nanomagnets. At high temperature, these materials behave as superparamagnets and their magnetization reversal occurs by thermal activation. At low temperature they become blocked, and their magnetic relaxation occurs via thermally assisted tunneling or pure quantum tunneling through the anisotropy barrier. We have conducted detailed experimental studies of the magnetization reversal in SMM material Mn12-acetate (Mn12) with S = 10. Low temperature measurements were conducted using micro-Hall effect magnetometry. We performed hysteresis and relaxation studies as a function of temperature, transverse field, and magnetization state of the sample. We identified magnetic sublevels that dominate the tunneling at a given field, temperature and magnetization. We observed a crossover between thermally assisted and pure quantum tunneling. The form of this crossover depends on the magnitude and direction of the applied field. This crossover is abrupt (first-order) and occurs in a narrow temperature interval (tunneling mechanisms in Mn12.

Facile synthesis, growth mechanism and reversible superhydrophobic and superhydrophilic properties of non-flaking CuO nanowires grown from porous copper substrates

International Nuclear Information System (INIS)

Zhang Qiaobao; Xu Daguo; Zhang Kaili; Hung, Tak Fu

2013-01-01

Reversible superhydrophobic and superhydrophilic surfaces based on porous substrates covered with CuO nanowires are developed in this study. A facile thermal oxidation method is used to synthesize non-flaking bicrystalline CuO nanowires on porous copper substrates in static air. The effects of thermal oxidation temperature and duration are systemically studied. The growth mechanism of the obtained non-flaking CuO nanowires is presented and the compression stress is believed to be the key driving force. The wettability of the CuO nanowires after chemical modification with trichloro(1H,1H,2H,2H-perfluorooctyl)silane is systemically investigated. The porous substrates covered with CuO nanowires exhibit excellent superhydrophobic performance with almost no water adhesion and no apparent drag resistance, and a maximum static water contact angle of 162 ± 2° is observed. Moreover, a rapid reversibly switchable wettability between superhydrophobic and superhydrophilic states is realized by the alternation of air–plasma treatment and surface fluorination. The porous substrates covered with CuO nanowires will find promising applications in surface and corrosion protection, liquid transportation, oil–water separation, and self-cleaning surfaces. (paper)

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase.

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Kopera, Huira C; Moldovan, John B; Morrish, Tammy A; Garcia-Perez, Jose Luis; Moran, John V

2011-12-20

Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that contain activities required for conventional retrotransposition by a mechanism termed target-site primed reverse transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic subunit-deficient CHO cell lines, which are defective for the nonhomologous end-joining DNA repair pathway, revealed an alternative endonuclease-independent (ENi) pathway for L1 retrotransposition. Interestingly, some ENi retrotransposition events in DNA protein kinase catalytic subunit-deficient cells are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease-defective L1 ribonucleoprotein particles can use oligonucleotide adapters that mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA. Importantly, these ribonucleoprotein particles also contain a nuclease activity that can process the oligonucleotide adapters before the initiation of reverse transcription. Finally, we demonstrate that ORF1p is not strictly required for ENi retrotransposition at dysfunctional telomeres. Thus, these data further highlight similarities between the mechanism of ENi L1 retrotransposition and telomerase.

Reverse leakage current characteristics of InGaN/GaN multiple quantum well ultraviolet/blue/green light-emitting diodes

Science.gov (United States)

Zhou, Shengjun; Lv, Jiajiang; Wu, Yini; Zhang, Yuan; Zheng, Chenju; Liu, Sheng

2018-05-01

We investigated the reverse leakage current characteristics of InGaN/GaN multiple quantum well (MQW) near-ultraviolet (NUV)/blue/green light-emitting diodes (LEDs). Experimental results showed that the NUV LED has the smallest reverse leakage current whereas the green LED has the largest. The reason is that the number of defects increases with increasing nominal indium content in InGaN/GaN MQWs. The mechanism of the reverse leakage current was analyzed by temperature-dependent current–voltage measurement and capacitance–voltage measurement. The reverse leakage currents of NUV/blue/green LEDs show similar conduction mechanisms: at low temperatures, the reverse leakage current of these LEDs is attributed to variable-range hopping (VRH) conduction; at high temperatures, the reverse leakage current of these LEDs is attributed to nearest-neighbor hopping (NNH) conduction, which is enhanced by the Poole–Frenkel effect.

Nonlinear Time-Reversal in a Wave Chaotic System

Science.gov (United States)

Frazier, Matthew; Taddese, Biniyam; Ott, Edward; Antonsen, Thomas; Anlage, Steven

2012-02-01

Time reversal mirrors are particularly simple to implement in wave chaotic systems and form the basis for a new class of sensors [1-3]. These sensors work by applying the quantum mechanical concepts of Loschmidt echo and fidelity decay to classical waves. The sensors make explicit use of time-reversal invariance and spatial reciprocity in a wave chaotic system to remotely measure the presence of small perturbations to the system. The underlying ray chaos increases the sensitivity to small perturbations throughout the volume explored by the waves. We extend our time-reversal mirror to include a discrete element with a nonlinear dynamical response. The initially injected pulse interacts with the nonlinear element, generating new frequency components originating at the element. By selectively filtering for and applying the time-reversal mirror to the new frequency components, we focus a pulse only onto the element, without knowledge of its location. Furthermore, we demonstrate transmission of arbitrary patterns of pulses to the element, creating a targeted communication channel to the exclusion of 'eavesdroppers' at other locations in the system. [1] Appl. Phys. Lett. 95, 114103 (2009) [2] J. Appl. Phys. 108, 1 (2010) [3] Acta Physica Polonica A 112, 569 (2007)

Sliding-induced non-uniform pre-tension governs robust and reversible adhesion: a revisit of adhesion mechanisms of geckos.

Science.gov (United States)

Cheng, Q H; Chen, B; Gao, H J; Zhang, Y W

2012-02-07

Several mechanisms have been proposed in the literature to explain the robust attachment and rapid, controllable detachment of geckos' feet on vertical walls or ceilings, yet, it is still debatable, which one is ultimately responsible for geckos' extraordinary capabilities for robust and reversible adhesion. In this paper, we re-examine some of the key movements of geckos' spatula pads and seta hairs during attachment and detachment, and propose a sequence of simple mechanical steps that would lead to the extraordinary properties of geckos observed in experiments. The central subject under study here is a linear distribution of pre-tension along the spatula pad induced by its sliding motion with respect to a surface. The resulting pre-tension, together with a control of setae's pulling force and angle, not only allows for robust and strong attachment, but also enables rapid and controllable detachment. We perform computational modelling and simulations to validate the following key steps of geckos' adhesion: (i) creation of a linear distribution of pre-tension in spatula through sliding, (ii) operation of an instability envelope controlled by setae's pulling force and angle, (iii) triggering of an adhesion instability leading to partial decohesion along the interface, and (iv) complete detachment of spatula through post-instability peeling. The present work not only reveals novel insights into the adhesion mechanism of geckos, but also develops a powerful numerical simulation approach as well as additional guidelines for bioinspired materials and devices.

Biaxially mechanical tuning of 2-D reversible and irreversible surface topologies through simultaneous and sequential wrinkling.

Science.gov (United States)

Yin, Jie; Yagüe, Jose Luis; Boyce, Mary C; Gleason, Karen K

2014-02-26

Controlled buckling is a facile means of structuring surfaces. The resulting ordered wrinkling topologies provide surface properties and features desired for multifunctional applications. Here, we study the biaxially dynamic tuning of two-dimensional wrinkled micropatterns under cyclic mechanical stretching/releasing/restretching simultaneously or sequentially. A biaxially prestretched PDMS substrate is coated with a stiff polymer deposited by initiated chemical vapor deposition (iCVD). Applying a mechanical release/restretch cycle in two directions loaded simultaneously or sequentially to the wrinkled system results in a variety of dynamic and tunable wrinkled geometries, the evolution of which is investigated using in situ optical profilometry, numerical simulations, and theoretical modeling. Results show that restretching ordered herringbone micropatterns, created through sequential release of biaxial prestrain, leads to reversible and repeatable surface topography. The initial flat surface and the same wrinkled herringbone pattern are obtained alternatively after cyclic release/restretch processes, owing to the highly ordered structure leaving no avenue for trapping irregular topological regions during cycling as further evidenced by the uniformity of strains distributions and negligible residual strain. Conversely, restretching disordered labyrinth micropatterns created through simultaneous release shows an irreversible surface topology whether after sequential or simultaneous restretching due to creation of irregular surface topologies with regions of highly concentrated strain upon formation of the labyrinth which then lead to residual strains and trapped topologies upon cycling; furthermore, these trapped topologies depend upon the subsequent strain histories as well as the cycle. The disordered labyrinth pattern varies after each cyclic release/restretch process, presenting residual shallow patterns instead of achieving a flat state. The ability to

Experiment-based thermal micromagnetic simulations of the magnetization reversal for ns-range clocked nanomagnetic logic

Science.gov (United States)

Ziemys, Grazvydas; Breitkreutz-v. Gamm, Stephan; Csaba, Gyorgy; Schmitt-Landsiedel, Doris; Becherer, Markus

2017-05-01

Extensive thermal micromagnetic simulations, based on experimental data and parameters, were performed to investigate the magnetization reversal in Co/Pt nanomagnets with locally reduced perpendicular anisotropy on the nanosecond range. The simulations were supported by experimental data gained on manufactured Co/Pt nanomagnets, as used in nanomagnetic logic. It is known that magnetization reversal is governed by two mechanisms. At pulse lengths longer than 100 ns, thermal activation dominates the magnetization reversal processes and follows the common accepted Arrhenius law. For pulse lengths shorter than 100 ns, the dynamic reversal dominates. With the help of thermal micro-magnetic simulations we found out that the point where the both mechanisms meet is determined by the damping constant α of the multilayer film stack. The optimization of ferromagnetic multilayer film stacks enables higher clocking rates with lower power consumption and, therefore, further improve the performance of pNML.

SMA bellows as reversible thermal sensors/actuators

International Nuclear Information System (INIS)

Damanpack, A R; Bodaghi, M; Liao, W H

2015-01-01

In this paper, the feasibility of reversible bellows made of shape memory alloys (SMAs) in sensory and actuated applications to transfer pressure and/or temperature into a linear motion is investigated. An analytical three-dimensional model is developed to simulate key features of SMAs including martensitic transformation, reorientation of martensite variants, the shape memory effect, and pseudo-elasticity. Axisymmetric two-dimensional theory of thermo-inelasticity based on the non-linear Green–Lagrange strain tensor is employed to derive the equilibrium equations. A finite element method along with an iterative incremental elastic-predictor–inelastic-corrector procedure is developed to solve the governing equations with both material and geometrical non-linearities. The feasibility of reversible SMA bellows in transferring pressure and/or temperature into a linear motion is numerically demonstrated. In this respect, the effects of geometric parameters, magnitude of thermo-mechanical loadings and end conditions on the performances of SMA bellows are evaluated and discussed in depth. This study provides pertinent results toward an efficient and reliable design of reversible thermally-driven SMA bellows. (paper)

Reversible martensitic ω-α transformation in Ti and Zr

International Nuclear Information System (INIS)

Al'shevskij, Yu.L.; Kul'nitskij, B.A.; Konyaev, Yu.S.; Rojtburt, A.L.

1985-01-01

The mechanism of phase transformation in pure Ti and Zr in samples with initial ω-structure, produced as a result of heating to 1400 K with subsequent increase in pressure up to 8 GPa and a sharp decrease in temperature and pressure to normal values, has been studies. As a result of α → β → ω transformation, occurring in the process of the above-mentioned treatment, grains of ω-phase with perfect rystal structure are formed. With ω-phase heating to 650 K formation of α-phase takes place, and it is accompanied by the appearance of characteristic martensitic relief on the sample surface. Subsequent application of high pressure results in the reverse α → ω transformation with the disappearance of surface relief.The data suggest that direct ω → α transformation while heating and reverse α → ω transformation under pressure are realized according to martensitic mechanism

Time reversal imaging, Inverse problems and Adjoint Tomography}

Science.gov (United States)

Montagner, J.; Larmat, C. S.; Capdeville, Y.; Kawakatsu, H.; Fink, M.

2010-12-01

With the increasing power of computers and numerical techniques (such as spectral element methods), it is possible to address a new class of seismological problems. The propagation of seismic waves in heterogeneous media is simulated more and more accurately and new applications developed, in particular time reversal methods and adjoint tomography in the three-dimensional Earth. Since the pioneering work of J. Claerbout, theorized by A. Tarantola, many similarities were found between time-reversal methods, cross-correlations techniques, inverse problems and adjoint tomography. By using normal mode theory, we generalize the scalar approach of Draeger and Fink (1999) and Lobkis and Weaver (2001) to the 3D- elastic Earth, for theoretically understanding time-reversal method on global scale. It is shown how to relate time-reversal methods on one hand, with auto-correlations of seismograms for source imaging and on the other hand, with cross-correlations between receivers for structural imaging and retrieving Green function. Time-reversal methods were successfully applied in the past to acoustic waves in many fields such as medical imaging, underwater acoustics, non destructive testing and to seismic waves in seismology for earthquake imaging. In the case of source imaging, time reversal techniques make it possible an automatic location in time and space as well as the retrieval of focal mechanism of earthquakes or unknown environmental sources . We present here some applications at the global scale of these techniques on synthetic tests and on real data, such as Sumatra-Andaman (Dec. 2004), Haiti (Jan. 2010), as well as glacial earthquakes and seismic hum.

Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

Science.gov (United States)

Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

1995-01-01

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase. Images Figure 1 PMID:7611281

Thermodynamic advantages of nuclear desalination through reverse osmosis

International Nuclear Information System (INIS)

Bhattacharyya, K.P.; Prabhakar, S.; Tewari, P.K.

2009-01-01

Seawater Reverse Osmosis (SWRO) integrated with nuclear power station has significant thermodynamic advantages since it can utilize the waste heat available in the condenser cooling circuit and electrical power from the nuclear power plant with provision for using grid power in case of exigencies and shared infrastructure. Coupling of RO plants to the reactor is simple and straightforward and power loss due to RO unit, resulting in the loss of load, does not impact reactor turbine. Product water contamination probability is also very less since it has in-built mechanical barrier. Preheat reverse osmosis desalination has many thermodynamic advantages and studies have indicated improved performance characteristics thereby leading to savings in operational cost. The significant advantages include the operational flexibility of the desalination systems even while power plant is non-operational and non-requirement of safety systems for resource utilization. This paper brings out a comprehensive assessment of reverse osmosis process as a stand-alone nuclear desalination system. (author)

Reversal of liver fibrosis: From fiction to reality.

Science.gov (United States)

Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

2017-04-01

In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

[Effect of silencing Bmi-1 expression in reversing cisplatin resistance in lung cancer cells and its mechanism].

Science.gov (United States)

Mao, Nan; He, Guansheng; Rao, Jinjun; Lv, Lin

2014-06-01

To investigate the effect of silencing Bmi-1 expression in reversing cisplatin resistance in human lung cancer cells and explore the possible mechanisms. Cisplatin-resistant A549/DDP cells with small interference RNA (siRNA)-mediated Bmi-1 expression silencing were examined for cisplatin sensitivity using MTT assay and alterations in cell cycle distribution and apoptosis with flow cytometry, and the changes in cell senescence was assessed using β-galactosidase staining. The protein expressions of Bmi-1, P14(ARF), P16(INK4a), P53, P21, Rb and ubi-H2AK119 in the cells were determined with Western blotting. A549/DDP cells showed significantly higher Bmi-1 expression than A549 cells. After siRNA-mediated Bmi-1 silencing, A549/DDP cells showed significantly enhanced cisplatin sensitivity with an increased IC50 from 40.3±4.1 µmol/L to 18.3±2.8 µmol/L (Pcisplatin possibly by regulating INK4a/ARF/Rb senescence pathway.

Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

Directory of Open Access Journals (Sweden)

Shuai Zhao

Full Text Available In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

The Organization of Behavior Over Time: Insights from Mid-Session Reversal

OpenAIRE

Rayburn-Reeves, Rebecca M.; Cook, Robert G.

2016-01-01

What are the mechanisms by which behavior is organized sequentially over time? The recently developed mid-session reversal (MSR) task offers new insights into this fundamental question. The typical MSR task is arranged to have a single reversed discrimination occurring in a consistent location within each session and across sessions. In this task, we examine the relevance of time, reinforcement, and other factors as the switching cue in the sequential modulation of control in MSR. New analyse...

Resolution of Loschmidt's paradox: The origin of irreversible behavior in reversible atomistic dynamics

International Nuclear Information System (INIS)

Holian, B.L.; Hoover, W.G.; Posch, H.A.

1987-01-01

We show that Nosromane-bar mechanics provides a link between computer simulations of nonequilibrium processes and real-world experiments. Reversible Nose-bar equations of motion, when used to constrain non- equilibrium boundary regions, generate stable dissipative behavior within an adjoining bulk sample governed by Newton's equations of motion. Thus, irreversible behavior consistent with the second law of thermodynamics arises from completely reversible microscopic motion. Loschmidt's reversibility paradox is surmounted by this Nose-bar-Newton system, because the steady-state nonequilibrium probability density in the many-body phase space is confined to a zero-volume attractor

Reverse capillary flow of condensed water through aligned multiwalled carbon nanotubes

International Nuclear Information System (INIS)

Yun, Jongju; Jeon, Wonjae; Alam Khan, Fakhre; Lee, Jinkee; Baik, Seunghyun

2015-01-01

Molecular transport through nanopores has recently received considerable attention as a result of advances in nanofabrication and nanomaterial synthesis technologies. Surprisingly, water transport investigations through carbon nanochannels resulted in two contradicting observations: extremely fast transport or rejection of water molecules. In this paper, we elucidate the mechanism of impeded water vapor transport through the interstitial space of aligned multiwalled carbon nanotubes (aligned-MWCNTs)—capillary condensation, agglomeration, reverse capillary flow, and removal by superhydrophobicity at the tip of the nanotubes. The origin of separation comes from the water’s phase change from gas to liquid, followed by reverse capillary flow. First, the saturation water vapor pressure is decreased in a confined space, which is favorable for the phase change of incoming water vapor into liquid drops. Once continuous water meniscus is formed between the nanotubes by the adsoprtion and agglomeration of water molecules, a high reverse Laplace pressure is induced in the mushroom-shaped liquid meniscus at the entry region of the aligned-MWCNTs. The reverse Laplace pressure can be significantly enhanced by decreasing the pore size. Finally, the droplets pushed backward by the reverse Laplace pressure can be removed by superhydrophobicity at the tip of the aligned-MWCNTs. The analytical analysis was also supported by experiments carried out using 4 mm-long aligned-MWCNTs with different intertube distances. The water rejection rate and the separation factor increased as the intertube distance decreased, resulting in 90% and 10, respectively, at an intertube distance of 4 nm. This mechanism and nanotube membrane may be useful for energy-efficient water vapor separation and dehumidification. (paper)

Reverse genetics with animal viruses. NSV reverse genetics

International Nuclear Information System (INIS)

Mebatsion, T.

2005-01-01

New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)

Two-Way 4D Printing: A Review on the Reversibility of 3D-Printed Shape Memory Materials

Directory of Open Access Journals (Sweden)

Amelia Yilin Lee

2017-10-01

Full Text Available The rapid development of additive manufacturing and advances in shape memory materials have fueled the progress of four-dimensional (4D printing. With the right external stimulus, the need for human interaction, sensors, and batteries will be eliminated, and by using additive manufacturing, more complex devices and parts can be produced. With the current understanding of shape memory mechanisms and with improved design for additive manufacturing, reversibility in 4D printing has recently been proven to be feasible. Conventional one-way 4D printing requires human interaction in the programming (or shape-setting phase, but reversible 4D printing, or two-way 4D printing, will fully eliminate the need for human interference, as the programming stage is replaced with another stimulus. This allows reversible 4D printed parts to be fully dependent on external stimuli; parts can also be potentially reused after every recovery, or even used in continuous cycles—an aspect that carries industrial appeal. This paper presents a review on the mechanisms of shape memory materials that have led to 4D printing, current findings regarding 4D printing in alloys and polymers, and their respective limitations. The reversibility of shape memory materials and their feasibility to be fabricated using three-dimensional (3D printing are summarized and critically analyzed. For reversible 4D printing, the methods of 3D printing, mechanisms used for actuation, and strategies to achieve reversibility are also highlighted. Finally, prospective future research directions in reversible 4D printing are suggested.

Reversal Learning in Humans and Gerbils: Dynamic Control Network Facilitates Learning.

Science.gov (United States)

Jarvers, Christian; Brosch, Tobias; Brechmann, André; Woldeit, Marie L; Schulz, Andreas L; Ohl, Frank W; Lommerzheim, Marcel; Neumann, Heiko

2016-01-01

Biologically plausible modeling of behavioral reinforcement learning tasks has seen great improvements over the past decades. Less work has been dedicated to tasks involving contingency reversals, i.e., tasks in which the original behavioral goal is reversed one or multiple times. The ability to adjust to such reversals is a key element of behavioral flexibility. Here, we investigate the neural mechanisms underlying contingency-reversal tasks. We first conduct experiments with humans and gerbils to demonstrate memory effects, including multiple reversals in which subjects (humans and animals) show a faster learning rate when a previously learned contingency re-appears. Motivated by recurrent mechanisms of learning and memory for object categories, we propose a network architecture which involves reinforcement learning to steer an orienting system that monitors the success in reward acquisition. We suggest that a model sensory system provides feature representations which are further processed by category-related subnetworks which constitute a neural analog of expert networks. Categories are selected dynamically in a competitive field and predict the expected reward. Learning occurs in sequentialized phases to selectively focus the weight adaptation to synapses in the hierarchical network and modulate their weight changes by a global modulator signal. The orienting subsystem itself learns to bias the competition in the presence of continuous monotonic reward accumulation. In case of sudden changes in the discrepancy of predicted and acquired reward the activated motor category can be switched. We suggest that this subsystem is composed of a hierarchically organized network of dis-inhibitory mechanisms, dubbed a dynamic control network (DCN), which resembles components of the basal ganglia. The DCN selectively activates an expert network, corresponding to the current behavioral strategy. The trace of the accumulated reward is monitored such that large sudden

Sex Reversal in Reptiles: Reproductive Oddity or Powerful Driver of Evolutionary Change?

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Holleley, Clare E; Sarre, Stephen D; O'Meally, Denis; Georges, Arthur

2016-01-01

Is sex a product of genes, the environment, or both? In this review, we describe the diversity of sex-determining mechanisms in reptiles, with a focus on systems that display gene-environment interactions. We summarise the field and laboratory-based evidence for the occurrence of environmental sex reversal in reptiles and ask whether this is a widespread evolutionary mechanism affecting the evolution of sex chromosomes and speciation in vertebrates. Sex determination systems exist across a continuum of genetic and environmental influences, blurring the lines between what was once considered a strict dichotomy between genetic sex determination and temperature-dependent sex determination. Across this spectrum, we identify the potential for sex reversal in species with clearly differentiated heteromorphic sex chromosomes (Pogona vitticeps, Bassiana duperreyi, Eremias multiocellata, Gekko japonicus), weakly differentiated homomorphic sex chromosomes (Niveoscincus ocellatus), and species with only a weak heritable predisposition for sex (Emys orbicularis, Trachemys scripta). We argue that sex reversal is widespread in reptiles (Testudines, Lacertidae, Agamidae, Scincidae, Gekkonidae) and has the potential to have an impact on individual fitness, resulting in reproductively, morphologically, and behaviourally unique phenotypes. Sex reversal is likely to be a powerful evolutionary force responsible for generating and maintaining lability and diversity in reptile sex-determining modes. © 2016 S. Karger AG, Basel.

Reversing flow causes passive shark scale actuation in a separating turbulent boundary layer

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Lang, Amy; Gemmell, Bradford; Motta, Phil; Habegger, Laura; Du Clos, Kevin; Devey, Sean; Stanley, Caleb; Santos, Leo

2017-11-01

Control of flow separation by shortfin mako skin in experiments has been demonstrated, but the mechanism is still poorly understood yet must be to some extent Re independent. The hypothesized mechanisms inherent in the shark skin for controlling flow separation are: (1) the scales, which are capable of being bristled only by reversing flow, inhibit flow reversal events from further development into larger-scale separation and (2) the cavities formed when scales bristle induces mixing of high momentum flow towards the wall thus energizing the flow close to the surface. Two studies were carried out to measure passive scale actuation caused by reversing flow. A small flow channel induced an unsteady, wake flow over the scales prompting reversing flow events and scale actuation. To resolve the flow and scale movements simultaneously we used specialized optics at high magnification (1 mm field of view) at 50,000 fps. In another study, 3D printed models of shark scales, or microflaps (bristling capability up to 50 degrees), were set into a flat plate. Using a tripped, turbulent boundary layer grown over the long flat plate and a localized adverse pressure gradient, a separation bubble was generated within which the microflaps were placed. Passive flow actuation of both shark scales and microflaps by reversing flow was observed. Funding from Army Research Office and NSF REU site Grant.

The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study

Directory of Open Access Journals (Sweden)

Marjan Hosseini

2014-09-01

Full Text Available Introduction: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI model of neuropathic pain. Methods: In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t. three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. Results: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001, mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001, cold allodynia (df: 24, 5; F= 6.96; p<0.001, and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001. The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24, mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75, cold allodynia (df: 24, 5; F= 0.8; p= -0.56, and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86. Conclusion: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. Also the effect of GABAA agonist is short term and its effectiveness gradually decreases by time.

Now at the Met: fine art of reversible sulfoxidation.

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Ilani, Tal; Fass, Deborah

2013-08-08

In this issue, Lee et al. (2013) exhibit methionine sulfoxidation in a new light. By bringing together two antagonistic enzymes affecting methionine redox state, the authors demonstrate that methionine oxidation constitutes a reversible, posttranslational regulatory mechanism, akin to protein phosphorylation. Copyright © 2013 Elsevier Inc. All rights reserved.

Energy reversible switching from amorphous metal based nanoelectromechanical switch

KAUST Repository

Mayet, Abdulilah M.; Smith, Casey; Hussain, Muhammad Mustafa

2013-01-01

We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young's modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young's modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

Energy reversible switching from amorphous metal based nanoelectromechanical switch

KAUST Repository

Mayet, Abdulilah M.

2013-08-01

We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young\\'s modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young\\'s modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

The Organization of Behavior Over Time: Insights from Mid-Session Reversal.

Science.gov (United States)

Rayburn-Reeves, Rebecca M; Cook, Robert G

2016-01-01

What are the mechanisms by which behavior is organized sequentially over time? The recently developed mid-session reversal (MSR) task offers new insights into this fundamental question. The typical MSR task is arranged to have a single reversed discrimination occurring in a consistent location within each session and across sessions. In this task, we examine the relevance of time, reinforcement, and other factors as the switching cue in the sequential modulation of control in MSR. New analyses also highlight some of the potential mechanisms underlying this serially organized behavior. MSR provides new evidence and we offer some ideas about how cues interact to compete for the control of behavior within and across sessions. We suggest that MSR is an excellent preparation for studying the competition among psychological states and their resolution toward action.

Thermal and mechanical pain sensitization in patients with osteoarthritis of the knee.

Science.gov (United States)

Bevilaqua-Grossi, Debora; Zanin, Marilia; Benedetti, Camila; Florencio, Lidiane; Oliveira, Anamaria

2018-02-26

The aim was to assess sensitization using quantitative sensory testing in mechanical and thermal modes in individuals with and without osteoarthritis (OA) of the knee. Pain thresholds were correlated with functionality, symptoms of depression and intensity of pain. Thirty control volunteers and 30 patients with OA of the knee were assessed. Punctate pain thresholds using Von Frey filaments and thermal pain thresholds using a Thermal Sensory Analyzer were evaluated in the periarticular region of the knee and forearm. Using a digital pressure algometer, pressure pain thresholds were assessed in the periarticular region of the knee and on the root exit zone on the lumbar and sacral spine. Punctate, pressure, and thermal pain thresholds differed significantly between participants with and without OA (p pain sensitization. Pressure pain thresholds also showed moderate and negative correlations with data on functionality, symptoms of depression and intensity of pain (-0.36  -0.56), contributing up to 30% of their variability. Allodynia and hyperalgesia were demonstrated in the OA group, suggesting central sensitization in patients with mild to moderate severity of joint damage. Correlation between mechanical hypersensitivity and psychosocial factors seems to be small, despite of its significance.

Removal of radionuclides from liquid streams by reverse osmosis

International Nuclear Information System (INIS)

Deshmukh, U.A.; Ramachandhran, V.; Misra, B.M.

1987-01-01

Separation of radionuclides in trace concentrations by cellulose acetate membranes has been under investigation in this laboratory, and the behaviour of some important radionuclides such as 137 Cs and 90 Sr under reverse osmosis has been reported earlier. The present work deals with a few other typical radionuclides such as 60 Co, 103 Ru and 131 I which are not fully amenable to conventional methods for their removal. Separation of these radionuclides from liquid streams by the reverse osmosis process was studied using a small reverse osmosis test cell. Various parameters like membrane porosity, applied pressure and feed activity levels were investigated. Cellulose acetate membranes offer reasonable separation of 60 Co, 103 Ru and 131 I radionuclides, indicating the potential of reverse osmosis for treatment of effluents containing these radioisotopes. The percent separation is found to be in the order of Co > Ru > I. The percent radioactive separation improves with increases in feed activity. The performance data are explained in terms of solution-diffusion mechanism. It appears that the separation of radionuclides is not governed by diffusion alone, but by the interaction of solutes with the membranes. (author)

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

OpenAIRE

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

2018-01-01

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

Neutrino helicity reversal and fundamental symmetries

International Nuclear Information System (INIS)

Jentschura, U D; Wundt, B J

2014-01-01

A rather elusive helicity reversal occurs in a gedanken experiment in which a massive left-handed Dirac neutrino, traveling at a velocity u < c, is overtaken on a highway by a speeding vehicle (traveling at velocity v with u < v < c). Namely, after passing the neutrino, looking back, one would see a right-handed neutrino (which has never been observed in nature). The Lorentz-invariant mass of the right-handed neutrino is still the same as before the passing. The gedanken experiment thus implies the existence of right-handed, light neutrinos, which are not completely sterile. Furthermore, overtaking a bunch of massive right-handed Dirac neutrinos leads to gradual de-sterilization. We discuss the helicity reversal and the concomitant sterilization and de-sterilization mechanisms by way of an illustrative example calculation, with a special emphasis on massive Dirac and Majorana neutrinos. We contrast the formalism with a modified Dirac neutrino described by a Dirac equation with a pseudoscalar mass term proportional to the fifth current. (paper)

Reversible Redox Chemistry of Azo Compounds for Sodium-Ion Batteries.

Science.gov (United States)

Luo, Chao; Xu, Gui-Liang; Ji, Xiao; Hou, Singyuk; Chen, Long; Wang, Fei; Jiang, Jianjun; Chen, Zonghai; Ren, Yang; Amine, Khalil; Wang, Chunsheng

2018-03-05

Sustainable sodium-ion batteries (SSIBs) using renewable organic electrodes are promising alternatives to lithium-ion batteries for the large-scale renewable energy storage. However, the lack of high-performance anode material impedes the development of SSIBs. Herein, we report a new type of organic anode material based on azo group for SSIBs. Azobenzene-4,4'-dicarboxylic acid sodium salt is used as a model to investigate the electrochemical behaviors and reaction mechanism of azo compound. It exhibits a reversible capacity of 170 mAh g -1 at 0.2C. When current density is increased to 20C, the reversible capacities of 98 mAh g -1 can be retained for 2000 cycles, demonstrating excellent cycling stability and high rate capability. The detailed characterizations reveal that azo group acts as an electrochemical active site to reversibly bond with Na + . The reversible redox chemistry between azo compound and Na ions offer opportunities for developing long-cycle-life and high-rate SSIBs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Non-reversible evolution of quantum chaotic system. Kinetic description

International Nuclear Information System (INIS)

Chotorlishvili, L.; Skrinnikov, V.

2008-01-01

It is well known that the appearance of non-reversibility in classical chaotic systems is connected with a local instability of phase trajectories relatively to a small change of initial conditions and parameters of the system. Classical chaotic systems reveal an exponential sensitivity to these changes. This leads to an exponential growth of initial error with time, and as the result after the statistical averaging over this error, the dynamics of the system becomes non-reversible. In spite of this, the question about the origin of non-reversibility in quantum case remains actual. The point is that the classical notion of instability of phase trajectories loses its sense during quantum consideration. The current work is dedicated to the clarification of the origin of non-reversibility in quantum chaotic systems. For this purpose we study a non-stationary dynamics of the chaotic quantum system. By analogy with classical chaos, we consider an influence of a small unavoidable error of the parameter of the system on the non-reversibility of the dynamics. It is shown in the Letter that due to the peculiarity of chaotic quantum systems, the statistical averaging over the small unavoidable error leads to the non-reversible transition from the pure state into the mixed one. The second part of the Letter is dedicated to the kinematic description of the chaotic quantum-mechanical system. Using the formalism of superoperators, a muster kinematic equation for chaotic quantum system was obtained from Liouville equation under a strict mathematical consideration

Mechanism of molecular transport in novel reverse-selective nanocomposite membranes

International Nuclear Information System (INIS)

Merkel, T.C.; Freeman, B.D.; Spontak, R.J.; Meakin, P.; Hill, A.J.; Monash University, VIC

2002-01-01

Full text: Polymer nanocomposites continue to receive tremendous attention as organic-inorganic hybrid materials exhibiting a wide range of interesting, as well as technologically relevant, properties. This work reports a novel use of polymer nanocomposites as reverse-selective membranes. We have found that physical dispersion of nonporous fumed silica [FS] into glassy poly(4-methyl-2-pentyne) [PMP] simultaneously enhances membrane permeability (by as much as 240%) and selectivity for large organic molecules over small permanent gases. This surprising observation, in stark contrast to conventional filled polymer systems, reflects silica-induced disruption of local polymer chain packing and, as discerned by positron annihilation lifetime spectroscopy [PALS], a resulting subtle increase in the size of free volume elements through which molecular transport occurs. Such nanoscale hybridization represents an innovative means of tuning the transport properties of glassy polymeric media through control of molecular ordering

An algebra of reversible computation.

Science.gov (United States)

Wang, Yong

2016-01-01

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

Mechanism of Chronic Pain in Rodent Brain Imaging

Science.gov (United States)

Chang, Pei-Ching

Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

On thermodynamic and microscopic reversibility

International Nuclear Information System (INIS)

Crooks, Gavin E

2011-01-01

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

Influence of 2 MeV electrons irradiation on gallium phosphide light-emitting diodes reverse currents

Directory of Open Access Journals (Sweden)

V. G. Vorobiov

2015-10-01

Full Text Available Results of reverse electrophysical characteristics study of red and green LEDs, initial and irradiated with 2 MeV electrons were given. It was found that reverse current was predominantly caused by carriers tunneling at Urev ≤ 9 V, and by the avalanche multiplication at Urev ≥ 13 V, in the range U = 9 ÷ 13 V both mechanisms are available. Current increase at high voltage areas (Urev > 19 V is limited by the base resistance of diode. In the case of significant reverse currents (I > 1 mA irradiation of diodes leads to the shift of reverse current-voltage characteristics into the high voltages direction.

Aberrant TRPV1 expression in heat hyperalgesia associated with trigeminal neuropathic pain.

Science.gov (United States)

Urano, Hiroko; Ara, Toshiaki; Fujinami, Yoshiaki; Hiraoka, B Yukihiro

2012-01-01

Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1) in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL) model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP) were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal

OpenAIRE

Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

2015-01-01

A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transf...

Constraining the reversing and non-reversing modes of the geodynamo. New insights from magnetostratigraphy.

Science.gov (United States)

Gallet, Y.; Pavlov, V.; Shatsillo, A.; Hulot, G.

2015-12-01

Constraining the evolution in the geomagnetic reversal frequency over hundreds of million years is not a trivial matter. Beyond the fact that there are long periods without reversals, known as superchrons, and periods with many reversals, the way the reversal frequency changes through time during reversing periods is still debated. A smooth evolution or a succession of stationary segments have both been suggested to account for the geomagnetic polarity time scale since the Middle-Late Jurassic. Sudden changes from a reversing mode to a non-reversing mode of the geodynamo may also well have happened, the switch between the two modes having then possibly been controlled by the thermal conditions at the core-mantle boundary. There is, nevertheless, a growing set of magnetostratigraphic data, which could help decipher a proper interpretation of the reversal history, in particular in the early Paleozoic and even during the Precambrian. Although yielding a fragmentary record, these data reveal the occurrence of both additional superchrons and periods characterized by extremely high, not to say extraordinary, magnetic reversal frequencies. In this talk, we will present a synthesis of these data, mainly obtained from Siberia, and discuss their implication for the magnetic reversal behavior over the past billion years.

Influence of time dependent longitudinal magnetic fields on the cooling process, exchange bias and magnetization reversal mechanism in FM core/AFM shell nanoparticles: a Monte Carlo study.

Science.gov (United States)

Yüksel, Yusuf; Akıncı, Ümit

2016-12-07

Using Monte Carlo simulations, we have investigated the dynamic phase transition properties of magnetic nanoparticles with ferromagnetic core coated by an antiferromagnetic shell structure. Effects of field amplitude and frequency on the thermal dependence of magnetizations, magnetization reversal mechanisms during hysteresis cycles, as well as on the exchange bias and coercive fields have been examined, and the feasibility of applying dynamic magnetic fields on the particle have been discussed for technological and biomedical purposes.

Mobile phase effects on the retention on polar columns with special attention to the dual hydrophilic interaction-reversed-phase liquid chromatography mechanism, a review.

Science.gov (United States)

Jandera, Pavel; Hájek, Tomáš

2018-01-01

Hydrophilic interaction liquid chromatography on polar columns in aqueous-organic mobile phases has become increasingly popular for the separation of many biologically important compounds in chemical, environmental, food, toxicological, and other samples. In spite of many new applications appearing in literature, the retention mechanism is still controversial. This review addresses recent progress in understanding of the retention models in hydrophilic interaction liquid chromatography. The main attention is focused on the role of water, both adsorbed by the column and contained in the bulk mobile phase. Further, the theoretical retention models in the isocratic and gradient elution modes are discussed. The dual hydrophilic interaction liquid chromatography reversed-phase retention mechanism on polar columns is treated in detail, especially with respect to the practical use in one- and two-dimensional liquid chromatography separations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The double-slit experiment and the time-reversed fire alarm

International Nuclear Information System (INIS)

Halabi, T.

2010-01-01

When both slits of the double-slit experiment are open, closing one paradoxically increases the detection rate at some points on the detection screen. Feynman famously warned that temptation to understand such a puzzling feature only draws into blind alleys. Nevertheless, we gain insight into this feature by drawing an analogy between the double-slit experiment and a time-reversed fire alarm. Much as closing the slit increases probability of a future detection, ruling out fire drill scenarios, having heard the fire alarm, increases probability of a past fire (using Bayesian inference). Classically, Bayesian inference is associated with computing probabilities of past events. We therefore identify this feature of the double-slit experiment with a time-reversed thermodynamic arrow. We believe that much of the enigma of quantum mechanics is simply due to some variation of time's arrow. In further support of this, we employ a plausible formulation of the thermodynamic arrow to derive an uncertainty in classical mechanics that is reminiscent of quantum uncertainty.

Role of NFkappaB in an animal model of complex regional pain syndrome-type I (CRPS-I).

Science.gov (United States)

de Mos, Marissa; Laferrière, André; Millecamps, Magali; Pilkington, Mercedes; Sturkenboom, Miriam C J M; Huygen, Frank J P M; Coderre, Terence J

2009-11-01

NFkappaB is involved in several pathogenic mechanisms that are believed to underlie the complex regional pain syndrome (CRPS), including ischemia, inflammation and sensitization. Chronic postischemia pain (CPIP) has been developed as an animal model that mimics the symptoms of CRPS-I. The possible involvement of NFkappaB in CRPS-I was studied using CPIP rats. Under sodium pentobarbital anesthesia, a tourniquet was placed around the rat left ankle joint, producing 3 hours of ischemia, followed by rapid reperfusion (IR injury). NFkappaB was measured in nuclear extracts of muscle and spinal cord tissue using ELISA. Moreover, the anti-allodynic (mechanical and cold) effect was tested for systemic, intrathecal, or intraplantar treatment with the NFkappaB inhibitor pyrrolidine dithiocarbamate (PDTC). At 2 and 48 hours after IR injury, NFkappaB was elevated in muscle and spinal cord of CPIP rats compared to shams. At 7 days, NFkappaB levels were normalized in muscle, but still elevated in spinal cord tissue. Systemic PDTC treatment relieved mechanical and cold allodynia in a dose-dependent manner, lasting for at least 3 hours. Intrathecal-but not intraplantar-administration also relieved mechanical allodynia. The results suggest that muscle and spinal NFkappaB plays a role in the pathogenesis of CPIP and potentially of human CRPS. Using the CPIP model, we demonstrate that NFkappaB is involved in the development of allodynia after a physical injury (ischemia and reperfusion) without direct nerve trauma. Since CPIP animals exhibit many features of human CRPS-I, this observation indicates a potential role for NFkappaB in human CRPS.

Emulsifier development for high-concentrated reverse emulsions

Directory of Open Access Journals (Sweden)

I.L. Kovalenko

2016-05-01

Full Text Available The reverse emulsions have found broad application in ore mining industry as matrixes of emulsion explosive substances and boring washing waters. The defining characteristic of reverse emulsions of industrial explosive substances is the high stability and immunity to crystallization. Aim: The aim of this work is to assess the mechanism of emulsifiers effect like SMO and some PIBSA-derivatives, that are most abundantly used in world practice, and also to develop an effective domestic emulsifier of reverse emulsions. Materials and methods: Using the semi-dynamic method with use of the reverse stalagmometer it was determined the decreasing in interfacial tension on “water / diesel fuel” border in the presence of 0.5 wt % sorbitan monooleate of various producers. Emulsions with use of the chosen emulsifiers using the dynamic mixer on the basis of monosolution of ammonium nitrate and diesel fuel have been produced. The emulsions have the following composition, wt %: ammonium nitrate – 76.8; water – 15.6; diesel fuel – 6.0; emulsifier – 1.6. Results: By the researches results of the interfacial tension “surfactant water / solution in diesel fuel”, the stability of emulsions using monosolution of ammonium nitrate and the IR spectrums of SMO of various producers it is established that presence in product of impurity of oleic acid, di- and trioleates leads to decreasing in interphase activity, increasing of emulsifier oil solubility and decreasing the resistance of emulsions to crystallization. On the basis of the spectral data analysis it is suggested about possibility of specific interaction on the mechanism of “spectral resonance” between emulsifiers of the PIBSA-MEA, LZX type and crystals nucleus of NH4NO3 ammonium nitrate in dispersed phase of emulsion. Amidation of vegetable oils by monoethanol amine is implemented at the reduced temperatures (90…100 °C. It was proved the availability mainly of fatty acids amides in product

The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

DEFF Research Database (Denmark)

Wieskopf, Jeffrey S; Mathur, Jayanti; Limapichat, Walrati

2015-01-01

expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated...... with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross...

Chemical kinetics and reaction mechanism

International Nuclear Information System (INIS)

Jung, Ou Sik; Park, Youn Yeol

1996-12-01

This book is about chemical kinetics and reaction mechanism. It consists of eleven chapters, which deal with reaction and reaction speed on reaction mechanism, simple reaction by rate expression, reversible reaction and simultaneous reaction, successive reaction, complicated reaction mechanism, assumption for reaction mechanism, transition state theory, successive reaction and oscillating reaction, reaction by solution, research method high except kinetics on reaction mechanism, high reaction of kinetics like pulsed radiolysis.

Quantum vertex model for reversible classical computing.

Science.gov (United States)

Chamon, C; Mucciolo, E R; Ruckenstein, A E; Yang, Z-C

2017-05-12

Mappings of classical computation onto statistical mechanics models have led to remarkable successes in addressing some complex computational problems. However, such mappings display thermodynamic phase transitions that may prevent reaching solution even for easy problems known to be solvable in polynomial time. Here we map universal reversible classical computations onto a planar vertex model that exhibits no bulk classical thermodynamic phase transition, independent of the computational circuit. Within our approach the solution of the computation is encoded in the ground state of the vertex model and its complexity is reflected in the dynamics of the relaxation of the system to its ground state. We use thermal annealing with and without 'learning' to explore typical computational problems. We also construct a mapping of the vertex model into the Chimera architecture of the D-Wave machine, initiating an approach to reversible classical computation based on state-of-the-art implementations of quantum annealing.

Diagnostic Accuracy of Quantitative Sensory Testing to Discriminate Inflammatory Toothache and Intraoral Neuropathic Pain.

Science.gov (United States)

Porporatti, André Luís; Costa, Yuri Martins; Stuginski-Barbosa, Juliana; Bonjardim, Leonardo Rigoldi; Duarte, Marco Antônio Hungaro; Conti, Paulo César Rodrigues

2015-10-01

A differential diagnosis between inflammatory toothache (IT) and intraoral neuropathic pain is challenging. The aim of this diagnostic study was to quantify somatosensory function of subjects with IT (acute pulpitis) and atypical odontalgia (AO, intraoral neuropathic pain) and healthy volunteers and to quantify how accurately quantitative sensory testing (QST) discriminates an IT or AO diagnosis. The sample consisted of 60 subjects equally divided (n = 20) into 3 groups: (1) IT, (2) AO, and (3) control. A sequence of 4 QST methods was performed over the dentoalveolar mucosa in the apical maxillar or mandibular area: mechanical detection threshold, pain detection threshold (PDT), dynamic mechanical allodynia, and temporal summation. One-way analysis of variance, Tukey post hoc analyses, and z score transformation were applied to the data. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of the QST methods were calculated (α = 5%). Somatosensory abnormalities were found for the AO group, which is consistent with a low detection threshold to touch and pain and the presence of mechanical allodynia. For the IT group, no somatosensory abnormality was observed when compared with the control group. The most accurate QST to discriminate the diagnostic differences between IT and healthy individuals is the PDT. The diagnostic differences between AO and healthy individuals and between IT and AO are best discriminated with the mechanical detection threshold, PDT, and dynamic mechanical allodynia. The proposed QST methods may aid in the differential diagnosis between IT and AO with strong accuracy and may be used as complementary diagnostic tests. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Quantum-Enhanced Sensing Based on Time Reversal of Nonlinear Dynamics.

Science.gov (United States)

Linnemann, D; Strobel, H; Muessel, W; Schulz, J; Lewis-Swan, R J; Kheruntsyan, K V; Oberthaler, M K

2016-07-01

We experimentally demonstrate a nonlinear detection scheme exploiting time-reversal dynamics that disentangles continuous variable entangled states for feasible readout. Spin-exchange dynamics of Bose-Einstein condensates is used as the nonlinear mechanism which not only generates entangled states but can also be time reversed by controlled phase imprinting. For demonstration of a quantum-enhanced measurement we construct an active atom SU(1,1) interferometer, where entangled state preparation and nonlinear readout both consist of parametric amplification. This scheme is capable of exhausting the quantum resource by detecting solely mean atom numbers. Controlled nonlinear transformations widen the spectrum of useful entangled states for applied quantum technologies.

Fast switching of bistable magnetic nanowires through collective spin reversal

Science.gov (United States)

Vindigni, Alessandro; Rettori, Angelo; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta; Novak, Miguel A.

2005-08-01

The use of magnetic nanowires as memory units is made possible by the exponential divergence of the characteristic time for magnetization reversal at low temperature, but the slow relaxation makes the manipulation of the frozen magnetic states difficult. We suggest that finite-size segments can show a fast switching if collective reversal of the spins is taken into account. This mechanism gives rise at low temperatures to a scaling law for the dynamic susceptibility that has been experimentally observed for the dilute molecular chain Co(hfac)2NitPhOMe. These results suggest a possible way of engineering nanowires for fast switching of the magnetization.

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

Science.gov (United States)

Dohanich, G P; Cada, D A

1989-12-01

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

Reverse logistics - a framework

NARCIS (Netherlands)

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

2002-01-01

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

Tubal Ligation Reversal

Science.gov (United States)

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

Segmental neuropathic pain does not develop in male rats with complete spinal transections.

Science.gov (United States)

Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D

2008-10-01

In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

Demonstrating the Effect of Precipitation on the Mechanical Stability of Fine-Grained Austenite in Reversion-Treated 301LN Stainless Steel

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Antti Järvenpää

2017-09-01

Full Text Available According to recent investigations, a huge difference exists in the mechanical stability of austenite between the grain-refined structure states obtained in reversion annealing at 800–700 °C or at 900 °C, in a 301LN type austenitic stainless steel. Precipitation of chromium nitride occurring at these lower temperatures has been argued to be the factor reducing the stability. To prove this argument, a fine-grained, very stable austenitic structure was created at 900 °C in 1 s, and subsequently annealed at lower temperatures between 850 and 750 °C, up to 1000 s. It was found that the subsequent annealing at 750 and 800 °C resulted in prominent gradual decrease of the mechanical stability under tensile straining, detectable after 10 s annealing duration and continued until 1000 s. Only minimal grain growth occurred, which decreased the stability very marginally. The degree of the stability drop followed the predicted kinetics of the Cr2N precipitation with regards as its dependence on annealing duration and temperature. Further, the tensile yield strength of the fine-grained structure increased slightly due to the annealing. The presence of nano-sized Cr2N particles was verified after 1000 s holding at 750 °C. These observations and predictions yield firm evidence for the imperative contribution of precipitation to the highly reduced mechanical stability of grain-refined austenite in this steel.

Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model.

Science.gov (United States)

Wilsey, Jared T; Block, Julie H

2018-01-01

Previous research suggests that the α 2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action. The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model. The depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone) polymer film containing 3% (w/w) clonidine HCl (MDT3). Fifty-two young adult mix Landrace pigs (9-11 kg) were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8). Group 2 received three placebo strips (PBO, n=8), placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8), Group 4 received two MDT3 and one PBO (n=8), and Group 5 received three MDT3 (n=8). Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8) or clonidine solution (Group 7, 225 µg/day, n=4). The surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg), but not clonidine (up to 225 µg), completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7. These data suggest that a sustained-release clonidine depot may be a viable nonopioid, nonamide anesthetic therapy for the treatment of acute postsurgical nociceptive sensitization.

Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

DEFF Research Database (Denmark)

Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I.

2016-01-01

In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic...

Magnetization reversal processes of single nanomagnets and their energy barrier

International Nuclear Information System (INIS)

Krone, P.; Makarov, D.; Albrecht, M.; Schrefl, T.; Suess, D.

2010-01-01

Micromagnetic simulations were performed to investigate the influence of geometry and magnetic anisotropy constant on energy barrier and magnetization reversal mechanism of individual bits important for the bit patterned media concept in magnetic data storage. It is shown that dependency of the energy barrier on magnetic and geometric properties of bits can be described by an analytical approach in the case of quasi-coherent magnetization rotation process. However, when the bit size exceeds a critical size, for which an incoherent magnetization reversal is preferred, the analytical approach becomes invalid and no self-consistent theory is available. By systematically investigating the influence of bit size on the magnetization reversal mode, it was found that the transition from quasi-coherent to incoherent magnetization reversal mode can still be described analytically if an activation volume is considered instead of the bit volume. In this case, the nucleation volume is an important parameter determining thermal stability of the bit. If the volume of the bit is larger than twice the activation volume, the energy barrier stays nearly constant; with further increase in bit size, no gain in thermal stability can be achieved.

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

Directory of Open Access Journals (Sweden)

Elphick Maurice R

2009-07-01

Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

Information criteria for quantifying loss of reversibility in parallelized KMC

Energy Technology Data Exchange (ETDEWEB)

Gourgoulias, Konstantinos, E-mail: gourgoul@math.umass.edu; Katsoulakis, Markos A., E-mail: markos@math.umass.edu; Rey-Bellet, Luc, E-mail: luc@math.umass.edu

2017-01-01

Parallel Kinetic Monte Carlo (KMC) is a potent tool to simulate stochastic particle systems efficiently. However, despite literature on quantifying domain decomposition errors of the particle system for this class of algorithms in the short and in the long time regime, no study yet explores and quantifies the loss of time-reversibility in Parallel KMC. Inspired by concepts from non-equilibrium statistical mechanics, we propose the entropy production per unit time, or entropy production rate, given in terms of an observable and a corresponding estimator, as a metric that quantifies the loss of reversibility. Typically, this is a quantity that cannot be computed explicitly for Parallel KMC, which is why we develop a posteriori estimators that have good scaling properties with respect to the size of the system. Through these estimators, we can connect the different parameters of the scheme, such as the communication time step of the parallelization, the choice of the domain decomposition, and the computational schedule, with its performance in controlling the loss of reversibility. From this point of view, the entropy production rate can be seen both as an information criterion to compare the reversibility of different parallel schemes and as a tool to diagnose reversibility issues with a particular scheme. As a demonstration, we use Sandia Lab's SPPARKS software to compare different parallelization schemes and different domain (lattice) decompositions.

Replication-dependent 65R→K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V

International Nuclear Information System (INIS)

Sharma, Prem L.; Nurpeisov, Viktoria; Lee, Kimberly; Skaggs, Sara; Di San Filippo, Christina Amat; Schinazi, Raymond F.

2004-01-01

Understanding of the mechanisms of interaction among nucleoside reverse transcriptase inhibitor (NRTI)-selected mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) coding sequence is essential for the design of newer drugs and for enhancing our vision of the structure function relationship among amino acids of the polymerase domain of HIV-1. Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics. A novel NRTI (-)-β-D-dioxolane-guanosine (DXG) is known to select in vitro either the 65R or 74V mutant virus (Antimicrob. Agents Chemother. 44 (2000) 1783). These mutations were not selected together during repeated passaging of the HIV-1 in the presence of this drug. To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background. Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R→K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication kinetic assays in MT-2 cells demonstrated that double mutant 65R + 74V is highly attenuated for replication and the initiation of reversion is related to the increase in RT activity. Additionally, the suppression of viral replication in the presence of DXG or under suboptimal human recombinant interleukin-2 leads to minimal or no 65R→K reversion. These observations provide evidence that 65R→K reversion in the double mutant 65R + 74V is dependent on a specific rate of viral replication in a pNL4-3 background. A similar phenomenon may occur in vivo, which may have implications for treatment management strategies

Intractable problems in reversible cellular automata

International Nuclear Information System (INIS)

Vatan, F.

1988-01-01

The billiard ball model, a classical mechanical system in which all parameters are real variables, can perform all digital computations. An eight-state, 11-neighbor reversible cellular automaton (an entirely discrete system in which all parameters are integer variables) can simulate this model. One of the natural problems for this system is to determine the shape of a container so that they initial specific distribution of gas molecules eventually leads to a predetermined distribution. This problem if PSPACE-complete. Related intractable and decidable problems are discussed as well

49 CFR 230.89 - Reverse gear.

Science.gov (United States)

2010-10-01

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

A photoactivated artificial muscle model unit: reversible, photoinduced sliding of nanosheets.

Science.gov (United States)

Nabetani, Yu; Takamura, Hazuki; Hayasaka, Yuika; Shimada, Tetsuya; Takagi, Shinsuke; Tachibana, Hiroshi; Masui, Dai; Tong, Zhiwei; Inoue, Haruo

2011-11-02

A novel photoactivated artificial muscle model unit is reported. Here we show that organic/inorganic hybrid nanosheets reversibly slide horizontally on a giant scale and the interlayer spaces in the layered hybrid structure shrink and expand vertically by photoirradiation. The sliding movement of the system on a giant scale is the first example of an artificial muscle model unit having much similarity with that in natural muscle fibrils. In particular, our layered hybrid molecular system exhibits a macroscopic morphological change on a giant scale (~1500 nm) relative to the molecular size of ~1 nm by means of a reversible sliding mechanism.

Objective sensory evaluation of the spread of complex regional pain syndrome.

Science.gov (United States)

Edinger, Lara; Schwartzman, Robert J; Ahmad, Ayesha; Erwin, Kirsten; Alexander, Guillermo M

2013-01-01

The spread of complex regional pain syndrome (CRPS) has been well documented. Many severe refractory long-standing patients have total body pain (TBP) that evolved from a single extremity injury. The purpose of this study was to document by objective sensory threshold testing the extent of body area involvement in 20 long-standing patients with CRPS who have TBP. A comparison of sensory threshold testing parameters between 20 long-standing refractory patients with CRPS who have TBP versus 10 healthy participants. Twenty patients with CRPS who stated that they suffered from total body pain were chosen from the Drexel University College of Medicine CRPS database. They were compared to 10 healthy participants that were age and gender matched to the patients with CRPS. The sensory parameters tested were: skin temperature; static and mechanical allodynia; thermal allodynia; mechanical hyperalgesia; after sensations following all sensory tests. The sites chosen for testing in the patients with CRPS were the most painful area in each of 8 body regions that comprised the total body area. Five patients with CRPS had signs of CRPS over 100% of their body (20%). One patient had pain over 87% and another had pain over 90% of their body area. The average percentage of body involvement was 62% (range 37% - 100%). All patients with CRPS had at least one sensory parameter abnormality in all body regions. All patients with CRPS had lower pain thresholds for static allodynia in all body areas, while 50% demonstrated a lower threshold for dynamic allodynia in all body regions compared to the healthy participants. Cold allodynia had a higher median pain rating on the Likert pain scale in all body areas versus healthy participants except for the chest, abdomen, and back. Eighty-five percent of the patients with CRPS had a significantly lower pain threshold for mechanical hyperalgesia in all body areas compared to the healthy participants. After sensations occurred after all sensory

Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

Science.gov (United States)

Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

2017-09-01

Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

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Tozaki-Saitoh Hidetoshi

2009-04-01

Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

Restorative glass: reversible, discreet restoration using structural glass components

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Faidra Oikonomopoulou

2017-12-01

Full Text Available The application of structural glass as the principal material in restoration and conservation practices is a distinguishable, yet discreet approach. The transparency of glass allows the simultaneous perception of the monument at both its original and present condition, preserving its historical and aesthetical integrity. Concurrently, the material’s unique mechanical properties enable the structural consolidation of the monument. As a proof of concept, the restoration of Lichtenberg Castle is proposed. Solid cast glass units are suggested to complete the missing parts, in respect to the existing construction technique and aesthetics of the original masonry. Aiming for a reversible system, the glass units are interlocking, ensuring the overall stability without necessitating permanent, adhesive connections. This results in an elegant and reversible intervention.

Reversible Communicating Processes

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Geoffrey Brown

2016-02-01

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

Ranolazine attenuation of CFA-induced mechanical hyperalgesia.

Science.gov (United States)

Casey, Gregory P; Roberts, Jomar S; Paul, Dennis; Diamond, Ivan; Gould, Harry J

2010-01-01

To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain. Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration. Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia. Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.

Magnetisation reversal on surface of Nd-Fe-B magnets

International Nuclear Information System (INIS)

Sun, H.; Woodward, R.; Street, R.

1998-01-01

Full text: Time dependent magnetisation processes on surface of isotropic and anisotropic Nd-Fe-B magnets were measured using a Magneto-Optic Magnetometer (MOM) and the data were analysed by means of the constitutive equation H = H(M, M). The surface magnetic viscosity parameter Λ (or fluctuation field H f ) was obtained. The activation volume v, which represents the volume of a negative magnetisation nuclei during a magnetisation reversal process was calculated from Λ. The results are compared with those of the corresponding bulk properties obtained by analysing the data measured using a Vibrating Sample Magnetometer (VSM). Similar to bulk materials, Λ for the surface magnetisation is nearly constant over a wide range of magnetisation for both isotropic and anisotropic Nd-Fe-B. However, the surface hysteresis loops are significantly different from the bulk materials, indicating a significant difference in the magnetisation reversal processes between the bulk and surface materials. The surface magnetisation reversal mechanism, its relation and influence to the bulk properties and therefore the performance of permanent magnet are discussed

Reversible storage of lithium in a rambutan-like tin-carbon electrode.

Science.gov (United States)

Deng, Da; Lee, Jim Yang

2009-01-01

Fruity electrodes: A simple bottom-up self-assembly method was used to fabricate rambutan-like tin-carbon (Sn@C) nanoarchitecture (see scheme, green Sn) to improve the reversible storage of lithium in tin. The mechanism of the growth of the pear-like hairs is explored.

The origin of Karaj dam basement sill marginal reversal by Soret fractionation

Science.gov (United States)

Maghdour-Mashhour, Reza; Esmaeily, Dariush

2010-05-01

The Karaj dam basement sill (KDBS), located North West of Tehran, northern Iran, is one of the several E-W-trending plutons in the Albourz Mountains. The KDBS consists of a layered series between upper and lower chilled margins. The rocks of the chilled margins are gabbroic in composition and porphyritic, with euhedral to subhedral plagioclase and clinopyroxene megacrysts up to 5 mm long. The rocks become coarse-grained toward the center of the sill and show a gradual transition from porphyritic to equigranular texture. Field and petrographic observations reveal a reverse trend in marginal units crystallization from the eutectic point to the main magma composition; i.e., the olivine-bearing gabbro (porphyritic chilled margin), which has a eutectic composition, crystallized prior to the marginal gabbros, which have a cotectic or near-cotectic composition, as plagioclase laths in the gabbroic unit are embedded in large crystals of clinopyroxene and this phenomenon is believed to result from the cotectic crystallization of plagioclase and clinopyroxene. Four major mechanisms are proposed and discussed in order to find the exact mechanism responsible for marginal reversal formation as following: 1) Crystal settling is a gravity-dependent mechanism and phenocrysts must have settled to form a layer at the bottom of the sill, showing sharp upper boundary which is not observable in KDBS. Besides, the reverse fractionation of inwardly-dipping sequence of mentioned sill occurs in layers with primary dips up to 55°. Consequently capability of marginal reversals to develop along steeply inclined chamber margins, by this mechanism is implausible. 2) Multiple injections of successive magma pulses fails to explain the origin of marginal reversal since the transition along the entire length of marginal reversal is gradual also there is no compositional break or chilled contact between two mentioned units of KDBS margin (Olivine-gabbro and marginal gabbro). 3) The idea of

Calculation of reverse flow in inverted U-Tubes of steam generator during natural circulation

International Nuclear Information System (INIS)

Yang Ruichang; Liu Jinggong; Liu Ruolei; Qin Shiwei; Huang Yanping

2010-01-01

The mechanism of reverse flow in inverted U-tubes of steam generators of pressurized water reactors during natural circulation is analyzed by using the full range characteristic curve of parallel U-tubes. A lumped-distributed model to calculate the reverse flow occurred in inverted U-tubes of real steam generators with a large number of U-tubes during natural circulation is developed. The model has the advantages of quick calculation and high accuracy for the analysis of reverse flow in inverted U-tubes of real steam generators with natural circulation. This model has been used to calculate the normal and reverse flows occurred in inverted U-tubes of a steam generator with natural circulation. The comparison of calculated results indicates a well agreement with that predicted by the model in which normal or reverse flow in each individual U-tube is analyzed, which verifies the reliability of the model developed in this paper. (authors)

Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal.

Science.gov (United States)

Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

2015-05-18

A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.

Reversible S-nitrosylation in an engineered azurin

Energy Technology Data Exchange (ETDEWEB)

Tian, Shiliang; Liu, Jing; Cowley, Ryan E.; Hosseinzadeh, Parisa; Marshall, Nicholas M.; Yu, Yang; Robinson, Howard; Nilges, Mark J.; Blackburn, Ninian J.; Solomon, Edward I.; Lu, Yi

2016-04-25

S-Nitrosothiols are known as reagents for NO storage and transportation and as regulators in many physiological processes. Although the S-nitrosylation catalysed by haem proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here, we report reversible insertion of NO into a copper–thiolate bond in an engineered copper centre in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential by deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine in metalloproteins, but also shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)–S(Cys)NO species. The fast, efficient and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.

Reverse Logistics Systems: Persepsi dan Harapan Konsumen

Directory of Open Access Journals (Sweden)

Farida Pulansari

2016-12-01

Full Text Available Complaint is a signal that indicates important information directly by customers. Complaint will give valuable information to company to plan recovery strategies to maintain customer satisfaction and loyalty. Hence, Electronic Waste (E-waste becomes a hot issue internationally, domestically and locally. There are many kind of regulations, strategy, methods or approach to minimize of E-waste. The goal of this research is design of House of Reverse Logistics (HRL to understanding the customer needs and wants for Reverse Logistics (RL implementation. This research adopted Quality Function Deployment (QFD method to construct the HRL. Differences among them are determination of the customer needs and wants. HRL insert five perspectives i.e. Input, Structure, Process, Output and Social & Organization. In other hand, QFD only inserts consumer perspective. The results showed the highest factors of consumer dissatisfaction comes from: 20% of third-party services mechanism, 10% from collaboration RL system (collection centers, recycling centers, disposal center ,10% comes the standardization of servicing system and 60% of others

Neuropathic pain and its treatment with ARA 290 and ketamine : overlapping pathways

NARCIS (Netherlands)

Swartjes, Maarten

2014-01-01

Neuropathic pain is a disabling disease with a mechanism consisting of several pathways that ultimately converge in the development and persistence tactile and cold allodynia. Pharmacological treatment is often inadequate and coincides with intolerable side effects. The spared nerve injury animal

The Geomagnetic Field During a Reversal

Science.gov (United States)

Heirtzler, James R.

2003-01-01

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

When global rule reversal meets local task switching: The neural mechanisms of coordinated behavioral adaptation to instructed multi-level demand changes.

Science.gov (United States)

Shi, Yiquan; Wolfensteller, Uta; Schubert, Torsten; Ruge, Hannes

2018-02-01

Cognitive flexibility is essential to cope with changing task demands and often it is necessary to adapt to combined changes in a coordinated manner. The present fMRI study examined how the brain implements such multi-level adaptation processes. Specifically, on a "local," hierarchically lower level, switching between two tasks was required across trials while the rules of each task remained unchanged for blocks of trials. On a "global" level regarding blocks of twelve trials, the task rules could reverse or remain the same. The current task was cued at the start of each trial while the current task rules were instructed before the start of a new block. We found that partly overlapping and partly segregated neural networks play different roles when coping with the combination of global rule reversal and local task switching. The fronto-parietal control network (FPN) supported the encoding of reversed rules at the time of explicit rule instruction. The same regions subsequently supported local task switching processes during actual implementation trials, irrespective of rule reversal condition. By contrast, a cortico-striatal network (CSN) including supplementary motor area and putamen was increasingly engaged across implementation trials and more so for rule reversal than for nonreversal blocks, irrespective of task switching condition. Together, these findings suggest that the brain accomplishes the coordinated adaptation to multi-level demand changes by distributing processing resources either across time (FPN for reversed rule encoding and later for task switching) or across regions (CSN for reversed rule implementation and FPN for concurrent task switching). © 2017 Wiley Periodicals, Inc.

Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain

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Wei Tzuping

2012-07-01

Full Text Available Abstract Tibia fracture in rats followed by cast immobilization leads to nociceptive, trophic, vascular and bone-related changes similar to those seen in Complex Regional Pain Syndrome (CRPS. Substance P (SP mediated neurogenic inflammation may be responsible for some of the signs of CRPS in humans. We therefore hypothesized that SP acting through the SP receptor (NK1 leads to the CRPS-like changes found in the rat model. In the present study, we intradermally injected rats with SP and monitored hindpaw mechanical allodynia, temperature, and thickness as well as tissue levels of tumor necrosis factor-α (TNF-α, interleukin 1β (IL-1β, interleukin 6 (IL-6, and nerve growth factor-β (NGF for 72 h. Anti-NGF antibody was utilized to block the effects of SP-induced NGF up-regulation. Fracture rats treated with the selective NK1 receptor antagonist LY303870 prior to cast removal were assessed for BrdU, a DNA synthesis marker, incorporation in skin cells to examine cellular proliferation. Bone microarchitecture was measured using micro computed tomography (μCT. We observed that: (1 SP intraplantar injection induced mechanical allodynia, warmth and edema as well as the expression of nociceptive mediators in the hindpaw skin of normal rats, (2 LY303870 administered intraperitoneally after fracture attenuated allodynia, hindpaw unweighting, warmth, and edema, as well as cytokine and NGF expression, (3 LY303870 blocked fracture-induced epidermal thickening and BrdU incorporation after fracture, (4 anti-NGF antibody blocked SP-induced allodynia but not warmth or edema, and (5 LY303870 had no effect on bone microarchitecture. Collectively our data indicate that SP acting through NK1 receptors supports the nociceptive and vascular components of CRPS, but not the bone-related changes.

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

2016-01-01

Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy. The online version of this article (doi:10.1186/s12885-016-2777-0) contains supplementary material, which is available to authorized users

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

Science.gov (United States)

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

2009-04-01

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

Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB phosphorylation in spinal cord of mice.

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Junzo Kamei

Full Text Available Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB in the spinal dorsal horn. Rikkunshito (RKT, a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

The Causes of Preference Reversal.

OpenAIRE

Tversky, Amos; Slovic, Paul; Kahneman, Daniel

1990-01-01

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

Applications of the solvation parameter model in reversed-phase liquid chromatography.

Science.gov (United States)

Poole, Colin F; Lenca, Nicole

2017-02-24

The solvation parameter model is widely used to provide insight into the retention mechanism in reversed-phase liquid chromatography, for column characterization, and in the development of surrogate chromatographic models for biopartitioning processes. The properties of the separation system are described by five system constants representing all possible intermolecular interactions for neutral molecules. The general model can be extended to include ions and enantiomers by adding new descriptors to encode the specific properties of these compounds. System maps provide a comprehensive overview of the separation system as a function of mobile phase composition and/or temperature for method development. The solvation parameter model has been applied to gradient elution separations but here theory and practice suggest a cautious approach since the interpretation of system and compound properties derived from its use are approximate. A growing application of the solvation parameter model in reversed-phase liquid chromatography is the screening of surrogate chromatographic systems for estimating biopartitioning properties. Throughout the discussion of the above topics success as well as known and likely deficiencies of the solvation parameter model are described with an emphasis on the role of the heterogeneous properties of the interphase region on the interpretation and understanding of the general retention mechanism in reversed-phase liquid chromatography for porous chemically bonded sorbents. Copyright © 2016 Elsevier B.V. All rights reserved.

ECOLOGICAL AND EVOLUTIONARY APPLICATIONS FOR ENVIRONMENTAL SEX REVERSAL OF FISH.

Science.gov (United States)

Mcnair, Alistair; Lokman, P Mark; Closs, Gerard P; Nakagawa, Shinichi

2015-03-01

Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof. We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR. Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.

Analysis of reverse flow in inverted U-tubes of steam generator under natural circulation condition

International Nuclear Information System (INIS)

Yang Ruichang; Liu Ruolei; Liu Jinggong; Qin Shiwei

2008-01-01

In this paper, we report on the analysis of reverse flow in inverted U-tubes of a steam generator under natural circulation condition. The mechanism of reverse flow in inverted U-tubes of the steam generator with natural circulation is graphically analyzed by using the full-range characteristic curve of parallel U-tubes. The mathematical model and numerical calculation method for analyzing the reverse flow in inverted U-tubes of the steam generator with natural circulation have been developed. The reverse flow in an inverted U-tube steam generator of a simulated pressurized water reactor with natural circulation in analyzed. Through the calculation, the mass flow rates of normal and reverse flows in individual U-tubes are obtained. The predicted sharp drop of the fluid temperature in the inlet plenum of the steam generator due to reverse flow agrees very well with the experimental data. This indicates that the developed mathematical model and solution method can be used to correctly predict the reverse flow in the inverted U-tubes of the steam generator with natural circulation. The obtained results also show that in the analysis of natural circulation flow in the primary circuit, the reverse flow in the inverted U-tubes of the steam generator must be taken into account. (author)

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

Science.gov (United States)

Liu, Cui-Cui; Zhang, Xin-Sheng; Ruan, Yu-Ting; Huang, Zhu-Xi; Zhang, Su-Bo; Liu, Meng; Luo, Hai-Jie; Wu, Shao-Ling; Ma, Chao

2017-08-01

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain. Copyright © 2017 the American Physiological Society.

A new digitized reverse correction method for hypoid gears based on a one-dimensional probe

Science.gov (United States)

Li, Tianxing; Li, Jubo; Deng, Xiaozhong; Yang, Jianjun; Li, Genggeng; Ma, Wensuo

2017-12-01

In order to improve the tooth surface geometric accuracy and transmission quality of hypoid gears, a new digitized reverse correction method is proposed based on the measurement data from a one-dimensional probe. The minimization of tooth surface geometrical deviations is realized from the perspective of mathematical analysis and reverse engineering. Combining the analysis of complex tooth surface generation principles and the measurement mechanism of one-dimensional probes, the mathematical relationship between the theoretical designed tooth surface, the actual machined tooth surface and the deviation tooth surface is established, the mapping relation between machine-tool settings and tooth surface deviations is derived, and the essential connection between the accurate calculation of tooth surface deviations and the reverse correction method of machine-tool settings is revealed. Furthermore, a reverse correction model of machine-tool settings is built, a reverse correction strategy is planned, and the minimization of tooth surface deviations is achieved by means of the method of numerical iterative reverse solution. On this basis, a digitized reverse correction system for hypoid gears is developed by the organic combination of numerical control generation, accurate measurement, computer numerical processing, and digitized correction. Finally, the correctness and practicability of the digitized reverse correction method are proved through a reverse correction experiment. The experimental results show that the tooth surface geometric deviations meet the engineering requirements after two trial cuts and one correction.

A novel behavioral assay for measuring cold sensation in mice.

Science.gov (United States)

Brenner, Daniel S; Golden, Judith P; Gereau, Robert W

2012-01-01

Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia.

Magnetotransport and magnetization reversal of electrodeposited multilayer nanowires

Science.gov (United States)

Tang, Xueti

2007-12-01

Electrodeposited magnetic multilayer nanowires are ideal materials to study nanoscale magnetism and the giant magnetoresistance (GMR) in the current-perpendicular-to-plane (CPP) geometry. This is because the diameter of each nanowire is uniform, the surface of the nanowire is smooth, and the thickness of both the magnetic and non-magnetic layers can be varied to either larger or smaller than the spin diffusion length which is an important parameter in magnetotransport study. In addition, the aspect ratio (layer-thickness/diameter) that is related to shape anisotropy can be varied for magnetization reversal study. There has been little understanding in the magnetization reversal mechanism of multilayer nanowires, which is complicated due to the dipolar interactions between magnetic layers in each nanowire and between nanowires. The objective of this work is to study the magnetization reversal mechanism of multilayer nanowires using a vibrating sample magnetometer (VSM), where various dipolar interactions are taken into account. Although multilayer nanowires are ideal for the study of the CPP-GMR effect, there remains technical difficulty in making an electrical contact with individual nanowires for the CPP-GMR measurements. In this work, a point-contact method using a conductive plunger tip was developed in-house, that enabled us to measure the CPP-GMR of selected multilayer nanowires in an array of vertically aligned nanowires in each sample. To examine the CPP-GMR and compare the results with theoretical models, the CPP-GMR data were systematically obtained from samples with various magnetic and non-magnetic layer thicknesses. It was found from VSM measurement that the magnetization reversal mode in electrodeposited CoNi/Cu multilayer nanowires depends on the shape and thickness of the CoNi layers where the mode in rod-shaped thick CoNi layers is different from that in disk-shaped thin CoNi layers. The reversal mode in coherent rotation or curling was determined

The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model.

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Qi-Liang Mao-Ying

Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.

Strength and reversibility of stereotypes for a rotary control with linear scales.

Science.gov (United States)

Chan, Alan H S; Chan, W H

2008-02-01

Using real mechanical controls, this experiment studied strength and reversibility of direction-of-motion stereotypes and response times for a rotary control with horizontal and vertical scales. Thirty-eight engineering undergraduates (34 men and 4 women) ages 23 to 47 years (M=29.8, SD=7.7) took part in the experiment voluntarily. The effects of instruction of change of pointer position and control plane on movement compatibility were analyzed with precise quantitative measures of strength and a reversibility index of stereotype. Comparisons of the strength and reversibility values of these two configurations with those of rotary control-circular display, rotary control-digital counter, four-way lever-circular display, and four-way lever-digital counter were made. The results of this study provided significant implications for the industrial design of control panels for improved human performance.

Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

Science.gov (United States)

Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

2017-09-01

Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of paclitaxel induced sensory polyneuropathy with "Catwalk" automated gait analysis in mice.

Directory of Open Access Journals (Sweden)

Petra Huehnchen

Full Text Available Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.

A survey of structure characterization methods for ultrafiltration and reverse osmosis membranes

NARCIS (Netherlands)

Smolders, C.A.; Mulder, M.H.V.; van der Velden, P.M.

1976-01-01

Asymmetric membranes consist of a thin skin, which is permselective to certain molecules in solution, and a porous support, serving as a mechanical support layer and also as a transport layer for the permeate. Both in ultrafiltration and in hyperfiltration (reverse osmosis) asymmetric membranes are

Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

Science.gov (United States)

Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

Tunable reverse-biased graphene/silicon heterojunction Schottky diode sensor.

Science.gov (United States)

Singh, Amol; Uddin, Ahsan; Sudarshan, Tangali; Koley, Goutam

2014-04-24

A new chemical sensor based on reverse-biased graphene/Si heterojunction diode has been developed that exhibits extremely high bias-dependent molecular detection sensitivity and low operating power. The device takes advantage of graphene's atomically thin nature, which enables molecular adsorption on its surface to directly alter graphene/Si interface barrier height, thus affecting the junction current exponentially when operated in reverse bias and resulting in ultrahigh sensitivity. By operating the device in reverse bias, the work function of graphene, and hence the barrier height at the graphene/Si heterointerface, can be controlled by the bias magnitude, leading to a wide tunability of the molecular detection sensitivity. Such sensitivity control is also possible by carefully selecting the graphene/Si heterojunction Schottky barrier height. Compared to a conventional graphene amperometric sensor fabricated on the same chip, the proposed sensor demonstrated 13 times higher sensitivity for NO₂ and 3 times higher for NH₃ in ambient conditions, while consuming ∼500 times less power for same magnitude of applied voltage bias. The sensing mechanism based on heterojunction Schottky barrier height change has been confirmed using capacitance-voltage measurements. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of cryptographic mechanisms used in ransomware CryptXXX v3

Directory of Open Access Journals (Sweden)

Michał Glet

2016-12-01

Full Text Available The main purpose of this paper was to analysis how malicious software is using cryptographic mechanisms. Reverse engineering were applied in order to discover mechanisms used in ransomware CryptXXX v3. At the end were given some useful advices how to improve CryptXXX.[b]Keyword:[/b] ransomware, software engineering, reverse engineering, RC4, RSA, malicious software

Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6

Directory of Open Access Journals (Sweden)

Yan Jin

2012-01-01

Full Text Available Abstract Background Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6 levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation. Results Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment. Conclusions Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses

A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

Directory of Open Access Journals (Sweden)

Wu Ann

2011-01-01

Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

Reverse logistics policy – differences between conservative and innovative reverse logistics management

Directory of Open Access Journals (Sweden)

Alena Klapalová

2013-01-01

Full Text Available One of the of the key barriers that hampers effective and efficient management of reverse flows detected within a number of empirical surveys and case studies focused on reverse logistics and/or return management is business (organisational policy, specifically lack of policy, deficiency in existing policy or inferior policy. Despite this fact, there is a gap in literature which would show some evidence from practice that innovative reverse logistics policy both can pay off and is associated with certain aspects of reverse logistics management. Such proof can have several implications. It can support the call for better understanding and more research of the linkages of reverse logistics with other corporate functions, promote the acceptation of strategic character of reverse logistics and stress the role of RL policy within the rest of overall corporate management.The aim of this paper is to contribute and to enrich the existing body of knowledge concerning the above-mentioned gap through presentation of survey results that was realized in 2012 among managers of 244 Czech firms. The results demonstrate the statistically significant association between the innovativeness of RL policy and profitability of firms, quality of RL planning, perception of RL importance, level of RL knowledge and perception of product innovation importance for firms’ competitiveness and frequency of product innovation. They also reveal statistically significant differences between firms with conservative and innovative RL policy and the perceived existence of some barriers to manage RL.

Geomagnetic Field During a Reversal

Science.gov (United States)

Heirtzler, J. R.

2003-01-01

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

APOBEC3G inhibits elongation of HIV-1 reverse transcripts.

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Kate N Bishop

2008-12-01

Full Text Available APOBEC3G (A3G is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.

Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex.

Directory of Open Access Journals (Sweden)

Maral Tajerian

Full Text Available Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC, and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and

Supercritical fluid reverse micelle separation

Science.gov (United States)

Fulton, J.L.; Smith, R.D.

1993-11-30

A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

r-Universal reversible logic gates

International Nuclear Information System (INIS)

Vos, A de; Storme, L

2004-01-01

Reversible logic plays a fundamental role both in ultra-low power electronics and in quantum computing. It is therefore important to know which reversible logic gates can be used as building block for the reversible implementation of an arbitrary boolean function and which cannot

Quantum reverse hypercontractivity

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

Introduction to reversible computing

CERN Document Server

Perumalla, Kalyan S

2013-01-01

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

Reverse Genetics Approaches for the Development of Influenza Vaccines

Science.gov (United States)

Nogales, Aitor; Martínez-Sobrido, Luis

2016-01-01

Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

A Study on Reverse Logistics

OpenAIRE

Reddy, Dhananjaya

2011-01-01

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

Quantum reversibility is relative, or does a quantum measurement reset initial conditions?

Science.gov (United States)

Zurek, Wojciech H

2018-07-13

I compare the role of the information in classical and quantum dynamics by examining the relation between information flows in measurements and the ability of observers to reverse evolutions. I show that in the Newtonian dynamics reversibility is unaffected by the observer's retention of the information about the measurement outcome. By contrast-even though quantum dynamics is unitary, hence, reversible-reversing quantum evolution that led to a measurement becomes, in principle, impossible for an observer who keeps the record of its outcome. Thus, quantum irreversibility can result from the information gain rather than just its loss-rather than just an increase of the (von Neumann) entropy. Recording of the outcome of the measurement resets, in effect, initial conditions within the observer's (branch of) the Universe. Nevertheless, I also show that the observer's friend-an agent who knows what measurement was successfully carried out and can confirm that the observer knows the outcome but resists his curiosity and does not find out the result-can, in principle, undo the measurement. This relativity of quantum reversibility sheds new light on the origin of the arrow of time and elucidates the role of information in classical and quantum physics. Quantum discord appears as a natural measure of the extent to which dissemination of information about the outcome affects the ability to reverse the measurement.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

Hybrid supercapacitors for reversible control of magnetism.

Science.gov (United States)

Molinari, Alan; Leufke, Philipp M; Reitz, Christian; Dasgupta, Subho; Witte, Ralf; Kruk, Robert; Hahn, Horst

2017-05-10

Electric field tuning of magnetism is one of the most intensely pursued research topics of recent times aiming at the development of new-generation low-power spintronics and microelectronics. However, a reversible magnetoelectric effect with an on/off ratio suitable for easy and precise device operation is yet to be achieved. Here we propose a novel route to robustly tune magnetism via the charging/discharging processes of hybrid supercapacitors, which involve electrostatic (electric-double-layer capacitance) and electrochemical (pseudocapacitance) doping. We use both charging mechanisms-occurring at the La 0.74 Sr 0.26 MnO 3 /ionic liquid interface to control the balance between ferromagnetic and non-ferromagnetic phases of La 1-x Sr x MnO 3 to an unprecedented extent. A magnetic modulation of up to ≈33% is reached above room temperature when applying an external potential of only about 2.0 V. Our case study intends to draw attention to new, reversible physico-chemical phenomena in the rather unexplored area of magnetoelectric supercapacitors.

Quinolone Resistance Reversion by Targeting the SOS Response

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E. Recacha

2017-10-01

Full Text Available Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs and dynamic (killing curves or flow cytometry methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs. Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h, and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy.

From monster to twin reversed arterial perfusion: a history of acardiac twins.

Science.gov (United States)

Obladen, Michael

2010-05-01

A human being born without heart and head, i.e., the acardius/acranius malformation, has been described since antiquity. Superstition and fear made it a mystical disorder, a sign of God's wrath. The inquisition ruled that acranic infants should not be baptized and located the soul in the brain. Acardia was not associated with twin gestation until the reports of Mery in 1720 and Winslow in 1740. In 1850, Meckel identified the pathogenetic mechanism as reversed perfusion due to large arterio-arterial and veno-venous anastomoses; he believed the heart would fail to develop or arrest during development, and the acardiac fetus would be maintained by arterial perfusion from the pump twin. In 1859, Claudius articulated that after normal initial development, the heart degenerates when reversed flow in the aorta leads to thrombosis. Today, it is assumed that both mechanisms may exist. With the advent of prenatal ultrasound diagnosis and radiofrequency ablation of the acardiac twin's circulation, it became possible to save the pump twin.

Model of reversible vesicular transport with exclusion

International Nuclear Information System (INIS)

Bressloff, Paul C; Karamched, Bhargav R

2016-01-01

A major question in neurobiology concerns the mechanics behind the motor-driven transport and delivery of vesicles to synaptic targets along the axon of a neuron. Experimental evidence suggests that the distribution of vesicles along the axon is relatively uniform and that vesicular delivery to synapses is reversible. A recent modeling study has made explicit the crucial role that reversibility in vesicular delivery to synapses plays in achieving uniformity in vesicle distribution, so called synaptic democracy (Bressloff et al 2015 Phys. Rev. Lett. 114 168101). In this paper we generalize the previous model by accounting for exclusion effects (hard-core repulsion) that may occur between molecular motor-cargo complexes (particles) moving along the same microtubule track. The resulting model takes the form of an exclusion process with four internal states, which distinguish between motile and stationary particles, and whether or not a particle is carrying vesicles. By applying a mean field approximation and an adiabatic approximation we reduce the system of ODEs describing the evolution of occupation numbers of the sites on a 1D lattice to a system of hydrodynamic equations in the continuum limit. We find that reversibility in vesicular delivery allows for synaptic democracy even in the presence of exclusion effects, although exclusion does exacerbate nonuniform distributions of vesicles in an axon when compared with a model without exclusion. We also uncover the relationship between our model and other models of exclusion processes with internal states. (paper)

Optimized reversible binary-coded decimal adders

DEFF Research Database (Denmark)

Thomsen, Michael Kirkedal; Glück, Robert

2008-01-01

Abstract Babu and Chowdhury [H.M.H. Babu, A.R. Chowdhury, Design of a compact reversible binary coded decimal adder circuit, Journal of Systems Architecture 52 (5) (2006) 272-282] recently proposed, in this journal, a reversible adder for binary-coded decimals. This paper corrects and optimizes...... their design. The optimized 1-decimal BCD full-adder, a 13 × 13 reversible logic circuit, is faster, and has lower circuit cost and less garbage bits. It can be used to build a fast reversible m-decimal BCD full-adder that has a delay of only m + 17 low-power reversible CMOS gates. For a 32-decimal (128-bit....... Keywords: Reversible logic circuit; Full-adder; Half-adder; Parallel adder; Binary-coded decimal; Application of reversible logic synthesis...

Posterior reversible encephalopathy syndrome (pres) in two clinical cases of eclampsia

International Nuclear Information System (INIS)

Hasbun H, Jorge; Rodriguez G, Marcelo; Miranda G, Gonzalo

2012-01-01

The Posterior Reversible Encephalopathy Syndrome is a neurological condition described on 1996, developed in patients with complex systemic conditions, especially pregnant women with pre eclampsia that at the same time presented neurological signs as seizures, headache, visual loss, and vomiting in addition to posterior brain edema, visible on neuroimaging and located in parietal and occipital lobes, that usually reverses completely. We present two clinical cases with Pres and eclampsia, antenatal and post-partum, both with seizure and confirmed brain edema with Nuclear Magnetic Resonance. Both had a favorable evolution after the anticonvulsant and anti-hypertensive therapy were done. We discuss the controversy over pathophysiological mechanisms, the new methods for diagnosis and management and the importance of multidisciplinary approach

Minimising reversion, using seawater and magnesium chloride, caused by the dissolution of tricalcium aluminate hexahydrate.

Science.gov (United States)

Palmer, Sara J; Frost, Ray L; Smith, Matthew K

2011-01-15

The increase in pH and aluminium concentration after the neutralisation of bauxite refinery residues is commonly known as reversion. This investigation reports the extent of reversion in synthetic supernatant liquor and possible methods to reduce reversion. This work is based on bauxite refinery residues produced from alumina refineries, where reversion is a real life situation in neutralised refinery residues. Tricalcium aluminate hexahydrate, a common phase in bauxite refinery residues, has been found to cause reversion. It has been established that reductions in both pH and aluminium from the seawater neutralisation process are due to the formation of 'Bayer' hydrotalcite Mg(7)Al(2)(OH)(18)(CO(3)(2-),SO(4)(2-))·xH(2)O. This is the primary mechanism involved in the removal of aluminium from solution. Increasing the volume of seawater used for the neutralisation process minimises the extent of reversion for both synthetic supernatant liquor and red mud slurry. The addition of MgCl(2)·6H(2)O also showed a reduction in reversion and confirmed that the decrease in aluminium and hydroxyl ions is due to the formation of Bayer hydrotalcite and not simply a dilution effect. Copyright © 2010 Elsevier Inc. All rights reserved.

An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

Science.gov (United States)

Dugan, Elizabeth A; Sagen, Jacqueline

2015-05-01

Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.

Mechanism of Cyclically Polarity Reversing Solar Magnetic Cycle as ...

Indian Academy of Sciences (India)

tribpo

solar dynamo mechanism that generates electric current and magnetic field by plasma flows ... rotating body in the Universe. We also mention a list ... verifications of any solar cycle dynamo theories of short and long term behaviors of the Sun, ...

Mechanisms for pituitary tumorigenesis: the plastic pituitary

OpenAIRE

Melmed, Shlomo

2003-01-01

The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplas...

Sugammadex to reverse neuromuscular blockade and provide optimal conditions for motor-evoked potential monitoring

Directory of Open Access Journals (Sweden)

Mehdi Trifa

2017-01-01

Full Text Available Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade (NMB via a mechanism that differs completely from acetylcholinesterase inhibitors. By encapsulating rocuronium, sugammadex can provide recovery of neuromuscular function even when there is a profound degree of NMB. We report anecdotal experience with the use of sugammadex to reverse NMB to facilitate intraoperative neurophysiological monitoring (motor evoked potentials in an adolescent with scoliosis during posterior spinal fusion. Its potential application in this unique clinical scenario is discussed, and potential dosing schemes are reviewed.

Post-training depletions of basolateral amygdala serotonin fail to disrupt discrimination, retention, or reversal learning

Directory of Open Access Journals (Sweden)

G. Jesus eOchoa

2015-05-01

Full Text Available In goal-directed pursuits, the basolateral amygdala (BLA is critical in learning about changes in the value of rewards. BLA-lesioned rats show enhanced reversal learning, a task employed to measure the flexibility of response to changes in reward. Similarly, there is a trend for enhanced discrimination learning, suggesting that BLA may modulate formation of stimulus-reward associations. There is a parallel literature on the importance of serotonin (5HT in new stimulus-reward and reversal learning. Recent postulations implicate 5HT in learning from punishment. Whereas dopaminergic involvement is critical in behavioral activation and reinforcement, 5HT may be most critical for aversive processing and behavioral inhibition, complementary cognitive processes. Given these findings, a 5HT-mediated mechanism in BLA may mediate the facilitated learning observed previously. The present study investigated the effects of selective 5HT lesions in BLA using 5,7-dihydroxytryptamine (5,7-DHT versus infusions of saline (Sham on discrimination, retention, and deterministic reversal learning. Rats were required to reach an 85% correct pairwise discrimination and single reversal criterion prior to surgery. Postoperatively, rats were then tested on the 1 retention of the pretreatment discrimination pair 2 discrimination of a novel pair and 3 reversal learning performance. We found statistically comparable preoperative learning rates between groups, intact postoperative retention, and unaltered novel discrimination and reversal learning in 5,7-DHT rats. These findings suggest that 5HT in BLA is not required for formation and flexible adjustment of new stimulus-reward associations when the strategy to efficiently solve the task has already been learned. Given the complementary role of orbitofrontal cortex in reward learning and its interconnectivity with BLA, these findings add to the list of dissociable mechanisms for BLA and orbitofrontal cortex in reward learning.

TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms

Czech Academy of Sciences Publication Activity Database

Uchytilová, Eva; Špicarová, Diana; Paleček, Jiří

2014-01-01

Roč. 10, č. 2014 (2014), s. 67 ISSN 1744-8069 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058; GA ČR(CZ) GPP303/12/P510 Institutional support: RVO:67985823 Keywords : SB366791 * TRPV1 * allodynia * hyperalgesia * surgical pain * spinal cord Subject RIV: FH - Neurology Impact factor: 3.654, year: 2014

The Two-Time Interpretation and Macroscopic Time-Reversibility

Directory of Open Access Journals (Sweden)

Yakir Aharonov

2017-03-01

Full Text Available The two-state vector formalism motivates a time-symmetric interpretation of quantum mechanics that entails a resolution of the measurement problem. We revisit a post-selection-assisted collapse model previously suggested by us, claiming that unlike the thermodynamic arrow of time, it can lead to reversible dynamics at the macroscopic level. In addition, the proposed scheme enables us to characterize the classical-quantum boundary. We discuss the limitations of this approach and its broad implications for other areas of physics.

The reversal phase of the bone-remodeling cycle

DEFF Research Database (Denmark)

Delaisse, Jean-Marie

2014-01-01

coincides with decreased osteoblast recruitment and impaired initiation of bone formation, that is, uncoupling. Overall, this review stresses that coupling does not only depend on molecules able to activate osteogenesis, but that it also demands the presence of osteoprogenitors and ordered cell......The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention...

Sex Reversal in Amphibians.

Science.gov (United States)

Flament, Stéphane

2016-01-01

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

Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

Science.gov (United States)

Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

2016-01-01

One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

What do reversible programs compute?

DEFF Research Database (Denmark)

Axelsen, Holger Bock; Glück, Robert

2011-01-01

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

Fundamentals of reversible flowchart languages

DEFF Research Database (Denmark)

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

2016-01-01

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

An FMRI Study of Olfactory Cues to Perception of Conspecific Stress

Science.gov (United States)

2010-04-01

Petrovic P, Ingvar M, Stone-Elander S, Petersson KM, Hansson P (1999) A PET activation study of dynamic mechanical allodynia in patients with...state on olfactory sensitivity suggest odor specificity. Biol Psychol 71: 244-247. 67. Mair RG, Bouffard JA, Engen T, Morton TH (1978) Olfactory

Effect of Reverse Bias Stress on Leakage Currents and Breakdown Voltages of Solid Tantalum Capacitors

Science.gov (United States)

Teverovsky, Alexander A.

2011-01-01

The majority of solid tantalum capacitors are produced by high-temperature sintering of a fine tantalum powder around a tantalum wire followed by electrolytic anodization that forms a thin amorphous Ta2O5 dielectric layer and pyrolysis of manganese nitrite on the oxide to create a conductive manganese dioxide electrode. A contact to tantalum wire is used as anode terminal and to the manganese layer as a cathode terminal of the device. This process results in formation of an asymmetric Ta -- Ta2O5 -- MnO2 capacitor that has different characteristics at forward (positive bias applied to tantalum) and reverse (positive bias applied to manganese cathode) voltages. Reverse bias currents might be several orders of magnitude larger than forward leakage currents so I-V characteristics of tantalum capacitors resemble characteristics of semiconductor rectifiers. Asymmetric I-V characteristics of Ta -- anodic Ta2O5 systems have been observed at different top electrode materials including metals, electrolytes, conductive polymers, and manganese oxide thus indicating that this phenomenon is likely related to the specifics of the Ta -- Ta2O5 interface. There have been multiple attempts to explain rectifying characteristics of capacitors employing anodic tantalum pentoxide dielectrics. A brief review of works related to reverse bias (RB) behavior of tantalum capacitors shows that the mechanism of conduction in Ta -- Ta2O5 systems is still not clear and more testing and analysis is necessary to understand the processes involved. If tantalum capacitors behave just as rectifiers, then the assessment of the safe reverse bias operating conditions would be a relatively simple task. Unfortunately, these parts can degrade with time under reverse bias significantly, and this further complicates analysis of the I-V characteristics and establishing safe operating areas of the parts. On other hand, time dependence of reverse currents might provide additional information for investigation of

Ion-containing reverse osmosis membranes obtained by radiation grafting method

International Nuclear Information System (INIS)

Hegazy, E.-S.A.; El-Assy, N.B.; Dessouki, A.M.; Shaker, M.M.

1989-01-01

Cationic membranes obtained by radiation grafting of aqueous acrylic acid onto low density polyethylene films followed by alkaline treatment to confer ionic character in the graft chains, were tested for reverse osmosis desalination of saline water. Selected physical properties of such membranes were investigated. The grafted membranes possess good mechanical and electrical properties. Water uptake for the alkali-treated membrane was much higher than that of the alkali-untreated one. The effect of operation time, degree of grafting, applied pressure and feed concentration on the water flux and salt rejection for the grafted membranes was investigated. Such cationic membranes showed good durability, thermal and chemical stability, acceptable water flux and salt rejection which may make them acceptable for practical use in reverse osmosis desalination of sea water. (author)

Increased reverse T3 concentration in patients with anorexia nerrosa

International Nuclear Information System (INIS)

Baranowska, B.; Kaniewski, M.; Zgliczynski, S.

1980-01-01

In 20 female patients with anorexia nervosa, aging 16 - 26 years, the thyroid function was estimated by +- determining TSH secretion in response to TRH, and serum thyroxine (T 4 ), 3,5,3'L-triiodothyronine (T 3 ) and 3,3',5'L-triiodothyronine (reverse T 3 ) concentrations. 14 healthy women of the same age were included into the control group. If compared with control group, a marked supression of TRH stimulated TSH secretion and a lowering of serum T 3 concentration was found in patients with anorexia nervosa. On the other hand, serum reverse T 3 concentration was markedly higher in patients with anorexia nervosa than in control ones. Gain of body weight leads to normalization of thyroid hormones level in the serum. Obtained results show for peripheral mechanism of described hormonal disorders. (author)

A novel behavioral assay for measuring cold sensation in mice.

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Daniel S Brenner

Full Text Available Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia.

Probing the energy barriers and magnetization reversal processes of nanoperforated membrane based percolated media

International Nuclear Information System (INIS)

Neu, V; Schultz, L; Schulze, C; Makarov, D; Albrecht, M; Faustini, M; Grosso, D; Lee, J; Kim, S-K; Suess, D

2013-01-01

Magnetization reversal processes in Co/Pt multilayers prepared on nanoperforated templates are probed by magnetization relaxation measurements. The signature of pinning controlled domain wall movement as expected for percolated media is identified. This contrasts with the nucleation-type reversal mechanism of a Co/Pt reference film prepared on a smooth substrate. A zero field energy barrier of 93k B T is determined by fluctuation field measurements and is elucidated by micromagnetic calculations using the nudged elastic band method. This value is sufficiently large to qualify the material as a promising percolated medium. (paper)

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid.

Science.gov (United States)

Drewes, Asbjørn-Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-07-28

Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.

Tough Self-Healing Elastomers by Molecular Enforced Integration of Covalent and Reversible Networks.

Science.gov (United States)

Wu, Jinrong; Cai, Li-Heng; Weitz, David A

2017-10-01

Self-healing polymers crosslinked by solely reversible bonds are intrinsically weaker than common covalently crosslinked networks. Introducing covalent crosslinks into a reversible network would improve mechanical strength. It is challenging, however, to apply this concept to "dry" elastomers, largely because reversible crosslinks such as hydrogen bonds are often polar motifs, whereas covalent crosslinks are nonpolar motifs. These two types of bonds are intrinsically immiscible without cosolvents. Here, we design and fabricate a hybrid polymer network by crosslinking randomly branched polymers carrying motifs that can form both reversible hydrogen bonds and permanent covalent crosslinks. The randomly branched polymer links such two types of bonds and forces them to mix on the molecular level without cosolvents. This enables a hybrid "dry" elastomer that is very tough with fracture energy 13500 Jm -2 comparable to that of natural rubber. Moreover, the elastomer can self-heal at room temperature with a recovered tensile strength 4 MPa, which is 30% of its original value, yet comparable to the pristine strength of existing self-healing polymers. The concept of forcing covalent and reversible bonds to mix at molecular scale to create a homogenous network is quite general and should enable development of tough, self-healing polymers of practical usage. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beta II plasma-gun mechanical design and construction

International Nuclear Information System (INIS)

Pedrotti, L.; Deis, G.; Wong, R.; Calderon, M.; Chargin, A.; Garner, D.

1979-01-01

The magnetized coaxial plasma gun (located on the east end of the Beta II facility at the Lawrence Livermore Laboratory) will be used to test a new method of initiating a field reversed mirror plasma. The field-reversed mirror is expected to improve the mirror-fusion reactor by enhancing the ratio of fusion power to injected power. This paper concentrates on the mechanical design and construction of the magnetized coaxial plasma gun and also discusses the diagnostic devices necessary to demonstrate the formation of field-reversed rings

A functional language for describing reversible logic

DEFF Research Database (Denmark)

Thomsen, Michael Kirkedal

2012-01-01

Reversible logic is a computational model where all gates are logically reversible and combined in circuits such that no values are lost or duplicated. This paper presents a novel functional language that is designed to describe only reversible logic circuits. The language includes high....... Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...... circuits. The flow relies on a reversible combinator language as an intermediate language....

Biofouling in reverse osmosis: phenomena, monitoring, controlling and remediation

Science.gov (United States)

Maddah, Hisham; Chogle, Aman

2017-10-01

This paper is a comprehensive review of biofouling in reverse osmosis modules where we have discussed the mechanism of biofouling. Water crisis is an issue of pandemic concern because of the steady rise in demand of drinking water. Overcoming biofouling is vital since we need to optimize expenses and quality of potable water production. Various kinds of microorganisms responsible for biofouling have been identified to develop better understanding of their attacking behavior enabling us to encounter the problem. Both primitive and advanced detection techniques have been studied for the monitoring of biofilm development on reverse osmosis membranes. Biofouling has a negative impact on membrane life as well as permeate flux and quality. Thus, a mathematical model has been presented for the calculation of normalized permeate flux for evaluating the extent of biofouling. It is concluded that biofouling can be controlled by the application of several physical and chemical remediation techniques.

Geomagnetic Reversals during the Phanerozoic.

Science.gov (United States)

McElhinny, M W

1971-04-09

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

Comparative study of reversible hydrogen storage in alkali-doped fulleranes

Energy Technology Data Exchange (ETDEWEB)

Teprovich, Joseph A.; Knight, Douglas A.; Peters, Brent [Clean Energy Directorate – Savannah River National Laboratory, Aiken, SC 29801 (United States); Zidan, Ragaiy, E-mail: ragaiy.zidan@srnl.doe.gov [Clean Energy Directorate – Savannah River National Laboratory, Aiken, SC 29801 (United States)

2013-12-15

Highlights: ► Catalytic effect of alkali metals of fullerane formation. ► Hydrogen storage properties of alkali metal hydrides and fullerene composites. ► Novel intercalation of Na and Li in the fullerene lattice. ► Reversible phase transformation of C{sub 60} from fcc to bcc upon de/rehydrogenation. ► Potential to enable to the formation of other carbon based hydrogen storage systems. -- Abstract: In this report we describe and compare the hydrogen storage properties of lithium and sodium doped fullerenes prepared via a solvent-assisted mixing process. For the preparation of these samples either NaH or LiH was utilized as the alkali metal source to make material based on either a Na{sub 6}C{sub 60} or Li{sub 6}C{sub 60}. Both of the alkali-doped materials can reversibly absorb and desorb hydrogen at much milder conditions than the starting materials used to make them (decomposition temperatures of NaH > 420 °C, LiH > 670 °C, and fullerane > 500 °C). The hydrogen storage properties of the materials were compared by TGA, isothermal desorption, and XRD analysis. It was determined that the sodium-doped material can reversibly store 4.0 wt.% H{sub 2} while the lithium doped material can reversibly store 5.0 wt.% H{sub 2} through a chemisorption mechanism indicated by the formation and measurement of C–H bonds. XRD analysis of the material demonstrated that a reversible phase transition between fcc and bcc occurs depending on the temperature at which the hydrogenation is performed. In either system the active hydrogen storage material resembles a hydrogenated fullerene (fullerane)

Comparative study of reversible hydrogen storage in alkali-doped fulleranes

International Nuclear Information System (INIS)

Teprovich, Joseph A.; Knight, Douglas A.; Peters, Brent; Zidan, Ragaiy

2013-01-01

Highlights: ► Catalytic effect of alkali metals of fullerane formation. ► Hydrogen storage properties of alkali metal hydrides and fullerene composites. ► Novel intercalation of Na and Li in the fullerene lattice. ► Reversible phase transformation of C 60 from fcc to bcc upon de/rehydrogenation. ► Potential to enable to the formation of other carbon based hydrogen storage systems. -- Abstract: In this report we describe and compare the hydrogen storage properties of lithium and sodium doped fullerenes prepared via a solvent-assisted mixing process. For the preparation of these samples either NaH or LiH was utilized as the alkali metal source to make material based on either a Na 6 C 60 or Li 6 C 60 . Both of the alkali-doped materials can reversibly absorb and desorb hydrogen at much milder conditions than the starting materials used to make them (decomposition temperatures of NaH > 420 °C, LiH > 670 °C, and fullerane > 500 °C). The hydrogen storage properties of the materials were compared by TGA, isothermal desorption, and XRD analysis. It was determined that the sodium-doped material can reversibly store 4.0 wt.% H 2 while the lithium doped material can reversibly store 5.0 wt.% H 2 through a chemisorption mechanism indicated by the formation and measurement of C–H bonds. XRD analysis of the material demonstrated that a reversible phase transition between fcc and bcc occurs depending on the temperature at which the hydrogenation is performed. In either system the active hydrogen storage material resembles a hydrogenated fullerene (fullerane)

Insights into pre-reversal paleosecular variation from stochastic models

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Klaudio ePeqini

2015-09-01

Full Text Available To provide insights on the paleosecular variation of the geomagnetic field and the mechanism of reversals, long time series of the dipolar magnetic moment are generated by two different stochastic models, known as the domino model and the inhomogeneous Lebovitz disk dynamo model, with initial values taken from the from paleomagnetic data. The former model considers mutual interactions of N macrospins embedded in a uniformly rotating medium, where random forcing and dissipation act on each macrospin. With an appropriate set of the model’s parameters values, the series generated by this model have similar statistical behaviour to the time series of the SHA.DIF.14K model. The latter model is an extension of the classical two-disk Rikitake model, considering N dynamo elements with appropriate interactions between them.We varied the parameters set of both models aiming at generating suitable time series with behaviour similar to the long time series of recent secular variation (SV. Such series are then extended to the near future, obtaining reversals in both cases of models. The analysis of the time series generated by simulating the models show that the reversals appears after a persistent period of low intensity geomagnetic field, as it is occurring in the present times.

Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

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Ru-Yin Tsai

2016-06-01

Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

Science.gov (United States)

Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

2014-08-01

Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensory symptom profiles and co-morbidities in painful radiculopathy.

Directory of Open Access Journals (Sweden)

Friederike Mahn

Full Text Available Painful radiculopathies (RAD and classical neuropathic pain syndromes (painful diabetic polyneuropathy, postherpetic neuralgia show differences how the patients express their sensory perceptions. Furthermore, several clinical trials with neuropathic pain medications failed in painful radiculopathy. Epidemiological and clinical data of 2094 patients with painful radiculopathy were collected within a cross sectional survey (painDETECT to describe demographic data and co-morbidities and to detect characteristic sensory abnormalities in patients with RAD and compare them with other neuropathic pain syndromes. Common co-morbidities in neuropathic pain (depression, sleep disturbance, anxiety do not differ considerably between the three conditions. Compared to other neuropathic pain syndromes touch-evoked allodynia and thermal hyperalgesia are relatively uncommon in RAD. One distinct sensory symptom pattern (sensory profile, i.e., severe painful attacks and pressure induced pain in combination with mild spontaneous pain, mild mechanical allodynia and thermal hyperalgesia, was found to be characteristic for RAD. Despite similarities in sensory symptoms there are two important differences between RAD and other neuropathic pain disorders: (1 The paucity of mechanical allodynia and thermal hyperalgesia might be explained by the fact that the site of the nerve lesion in RAD is often located proximal to the dorsal root ganglion. (2 The distinct sensory profile found in RAD might be explained by compression-induced ectopic discharges from a dorsal root and not necessarily by nerve damage. These differences in pathogenesis might explain why medications effective in DPN and PHN failed to demonstrate efficacy in RAD.

Impact of drag reducing polymers on the onset of instability in a pipe with reverse flow

Science.gov (United States)

Shashank, H. J.; Sreenivas, K. R.

2014-11-01

The objective of this study is to understand the mechanism by which drag reducing polymer (DRP) additives modify turbulent flow, so as to reduce turbulent drag. Reverse flow in a pipe occurs when the fluid close to the wall moves in an opposite direction to that of the core fluid. Reverse flow is established by using a piston-cylinder mechanism, the programmed motion of which imparts a known impulse to the fluid. When the piston is stopped at the end of the stroke, fluid inertia makes the core of the flow to continue in the same direction. In order to conserve mass, reverse flow is established close to the wall. An inflection point is thus formed, leading to flow instability above a critical Reynolds number. Dye and streak flow visualization experiments are performed to highlight the impact of DRP additives (polyethylene oxide, PEO, dissolved in water). The time of onset of the instability and the wavelength of the observed instability are studied in systems with and without DRP additives. This study will provide further insight into the phenomenon of turbulent polymer drag reduction.

Simultaneous and spontaneous reversal of positional nystagmus; an unusual peripheral sign of benign paroxysmal positional vertigo

Directory of Open Access Journals (Sweden)

Sertac Yetiser, MD

2017-06-01

Full Text Available Direction-changing positional nystagmus is generally thought to be of central origin. Reversal of initial positional nystagmus during maintaining the head position in patients with benign paroxysmal positional vertigo (BPPV is quite unusual and could be a sign of peripheral pathology. Vestibular reflex adaptation, simultaneous co-existence of canalolithiasis and cupulolithiasis in the same or both ears and changing in direction of debris movement have been proposed for the mechanism of this phenomenon. This can be a sign of simultaneous ampullopedal and ampulofugal flows during single head movement. This double-phase pattern of flow causing reversal of positional nystagmus could be related with the amount, location and dispersal of otolithic debris inside the membranous labyrinth. Four patients (3 lateral canal canalolithiasis and 1 posterior canal with reversing spontaneous nystagmus among 530 patients with BPPV have been identified in our clinic. They have been cured with standard re-positioning maneuvers. Endolymphatic reflux theory has been proposed as the underlying mechanism for unusual behavior of otolithic debris.

Dissolution of alpha-prime precipitates in thermally embrittled S2205-duplex steels during reversion-heat treatment