Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.
Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W
2016-11-01
Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.
Nucleosome exclusion from the interspecies-conserved central AT-rich region of the Ars insulator.
Takagi, Haruna; Inai, Yuta; Watanabe, Shun-ichiro; Tatemoto, Sayuri; Yajima, Mamiko; Akasaka, Koji; Yamamoto, Takashi; Sakamoto, Naoaki
2012-01-01
The Ars insulator is a boundary element identified in the upstream region of the arylsulfatase (HpArs) gene in the sea urchin, Hemicentrotus pulcherrimus, and possesses the ability to both block enhancer-promoter communications and protect transgenes from silent chromatin. To understand the molecular mechanism of the Ars insulator, we investigated the correlation between chromatin structure, DNA structure and insulator activity. Nuclease digestion of nuclei isolated from sea urchin embryos revealed the presence of a nuclease-hypersensitive site within the Ars insulator. Analysis of micrococcal nuclease-sensitive sites in the Ars insulator, reconstituted with nucleosomes, showed the exclusion of nucleosomes from the central AT-rich region. Furthermore, the central AT-rich region in naked DNA was sensitive to nucleotide base modification by diethylpyrocarbonate (DEPC). These observations suggest that non-B-DNA structures in the central AT-rich region may inhibit nucleosomal formation, which leads to nuclease hypersensitivity. Furthermore, comparison of nucleotide sequences between the HpArs gene and its ortholog in Strongylocentrotus purpuratus revealed that the central AT-rich region of the Ars insulator is conserved, and this conserved region showed significant enhancer blocking activity. These results suggest that the central AT-rich nucleosome-free region plays an important role in the function of the Ars insulator.
Moore, Eugene L; Haspel, Gal; Libersat, Frederic; Adams, Michael E
2006-07-01
The wasp Ampulex compressa injects venom directly into the prothoracic ganglion of its cockroach host to induce a transient paralysis of the front legs. To identify the biochemical basis for this paralysis, we separated venom components according to molecular size and tested fractions for inhibition of synaptic transmission at the cockroach cercal-giant synapse. Only fractions in the low molecular weight range (<2 kDa) caused synaptic block. Dabsylation of venom components and analysis by HPLC and MALDI-TOF-MS revealed high levels of GABA (25 mM), and its receptor agonists beta-alanine (18 mM), and taurine (9 mM) in the active fractions. Each component produces transient block of synaptic transmission at the cercal-giant synapse and block of efferent motor output from the prothoracic ganglion, which mimics effects produced by injection of whole venom. Whole venom evokes picrotoxin-sensitive chloride currents in cockroach central neurons, consistent with a GABAergic action. Together these data demonstrate that Ampulex utilizes GABAergic chloride channel activation as a strategy for central synaptic block to induce transient and focal leg paralysis in its host. Copyright 2006 Wiley Periodicals, Inc.
Levy, Dan; Jakubowski, Moshe; Burstein, Rami
2004-01-01
Triptans are 5HT1B/1D receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT1B/1D receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization. PMID:15016917
Levy, Dan; Jakubowski, Moshe; Burstein, Rami
2004-03-23
Triptans are 5HT(1B/1D) receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT(1B/1D) receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization.
Mehta, V; Snidvongs, S; Ghai, B; Langford, R; Wodehouse, T
2017-06-01
Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Zhang, Juanjuan; Mense, Siegfried; Treede, Rolf-Detlef; Hoheisel, Ulrich
2017-10-01
In an animal model of nonspecific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues. To block microglial activation, minocycline was continuously administered intrathecally starting 1 day before or 2 days after the first NGF injection. The glia inhibitor fluorocitrate that also blocks astrocyte activation was administrated 2 days after the first injection. Minocycline applied before the first NGF injection reduced the manifest sensitization after the second NGF injection to control values. The proportion of neurons responsive to stimulation of deep tissues was reduced from 50% to 17.7% ( P < 0.01). No significant changes occurred when minocycline was applied after the first injection. In contrast, fluorocitrate administrated after the first NGF injection reduced significantly the proportion of neurons with deep input (15.8%, P < 0.01). A block of glia activation had no significant effect on the increased resting activity. The data suggest that blocking microglial activation prevented the NGF-induced latent spinal sensitization, whereas blocking astrocyte activation reversed it. The induction of spinal neuronal sensitization in this pain model appears to depend on microglia activation, whereas its maintenance is regulated by activated astrocytes. NEW & NOTEWORTHY Activated microglia and astrocytes mediate the latent sensitization induced by nerve growth factor in dorsal horn neurons that receive input from deep tissues of the low back. These processes may contribute to nonspecific low back pain. Copyright © 2017 the American Physiological Society.
A role for central nervous system PPAR-γ in the regulation of energy balance.
Ryan, Karen K; Li, Bailing; Grayson, Bernadette E; Matter, Emily K; Woods, Stephen C; Seeley, Randy J
2011-05-01
The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity.
Block 3. Central view of Block 3 observed from the ...
Block 3. Central view of Block 3 observed from the west to the east. This photograph reveals the alignment of trees within the central path of the park. In addition, this photograph exposes broken bricks aligning tree beds - Skyline Park, 1500-1800 Arapaho Street, Denver, Denver County, CO
Huang, Yung-Jen; Grau, James W
2018-05-02
Activation of pain (nociceptive) fibers can sensitize neural circuits within the spinal cord, inducing an increase in excitability (central sensitization) that can foster chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. In adult animals, the co-transporter KCC2 maintains a low intracellular concentration of the anion Cl - . As a result, when the GABA-A receptor is engaged, Cl - flows in the neuron which has a hyperpolarizing (inhibitory) effect. Spinal cord injury (SCI) can down-regulate KCC2 and reverse the flow of Cl - . Under these conditions, engaging the GABA-A receptor can have a depolarizing (excitatory) effect that fosters the development of nociceptive sensitization. The present paper explores how SCI alters GABA function and provides evidence that the loss of descending fibers alters pain transmission to the brain. Prior work has shown that, after SCI, administration of a GABA-A antagonist blocks the development of capsaicin-induced nociceptive sensitization, implying that GABA release plays an essential role. This excitatory effect is linked to serotonergic (5HT) fibers that descend through the dorsolateral funiculus (DLF) and impact spinal function via the 5HT-1A receptor. Supporting this, blocking the 5HT-1A receptor, or lesioning the DLF, emulated the effect of SCI. Conversely, spinal application of a 5HT-1A agonist up-regulated KCC2 and reversed the effect of bicuculline treatment. Finally, lesioning the DLF reversed how a GABA-A antagonist affects a capsaicin-induced aversion in a place conditioning task; in sham operated animals, bicuculline enhanced aversion whereas in DLF-lesioned rats biciculline had an antinociceptive effect. Copyright © 2018 Elsevier Inc. All rights reserved.
Maniscalco, James W; Zheng, Huiyuan; Gordon, Patrick J; Rinaman, Linda
2015-07-29
Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. The results from this study reveal a potential central mechanism for the "metabolic tuning" of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats, reduces or blocks the ability of acute stress to activate hindbrain neurons that are immunoreactive for either prolactin-releasing peptide or glucagon-like peptide 1, and attenuates the activation of their stress-sensitive projection targets in the limbic forebrain. In nonfasted rats, central antagonism of glucagon-like peptide 1 receptors partially mimics the effect of an overnight fast by blocking the ability of acute stress to inhibit food intake, and by attenuating stress-induced activation of hindbrain and limbic forebrain neurons. We propose that caloric restriction attenuates behavioral and physiological responses to acute stress by "silencing" central glucagon-like peptide 1 signaling pathways. Copyright © 2015 the authors 0270-6474/15/3510701-14$15.00/0.
Maniscalco, James W.; Zheng, Huiyuan; Gordon, Patrick J.
2015-01-01
Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast “silences” GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. SIGNIFICANCE STATEMENT The results from this study reveal a potential central mechanism for the “metabolic tuning” of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats, reduces or blocks the ability of acute stress to activate hindbrain neurons that are immunoreactive for either prolactin-releasing peptide or glucagon-like peptide 1, and attenuates the activation of their stress-sensitive projection targets in the limbic forebrain. In nonfasted rats, central antagonism of glucagon-like peptide 1 receptors partially mimics the effect of an overnight fast by blocking the ability of acute stress to inhibit food intake, and by attenuating stress-induced activation of hindbrain and limbic forebrain neurons. We propose that caloric restriction attenuates behavioral and physiological responses to acute stress by “silencing” central glucagon-like peptide 1 signaling pathways. PMID:26224855
Thermoregulation in multiple sclerosis.
Davis, Scott L; Wilson, Thad E; White, Andrea T; Frohman, Elliot M
2010-11-01
Multiple sclerosis (MS) is a progressive neurological disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on five main themes regarding the current understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2) central regulation of body temperature; 3) thermoregulatory effector responses; 4) heat-induced fatigue; and 5) countermeasures to improve or maintain function during thermal stress. Heat sensitivity in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block, which can be quantitatively characterized using precise measurements of ocular movements. MS lesions can also occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Fatigue during thermal stress is common in MS and results in decreased motor function and increased symptomatology likely due to impairments in central conduction. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacological) for the MS patient to preserve function and decrease symptom worsening during heat stress.
Effects of procaine on a central neuron of the snail, Achatina fulica Ferussac.
Lin, Chia-Hsien; Tsai, Ming-Cheng
2005-02-18
Effects of procaine on a central neuron (RP1) of the giant African snail (Achatina fulica Ferussac) were studied pharmacologically. The RP1 neuron showed spontaneous firing of action potential. Extra-cellular application of procaine (10 mM) reversibly elicited bursts of potential. The bursts of potential elicited by procaine were not blocked after administration of (1) prazosin, propranolol, atropine, d-tubocurarine, (2) calcium-free solution, (3) ryanodine (4) pretreatment with KT-5720 or chelerythrine. The bursts of potential elicited by procaine were blocked by adding U73122 (10 microM) and the bursts of potential were decreased if physiological sodium ion was replaced with lithium ion or incubated with either neomycin (3.5 mM) or high magnesium solution (30 mM). Preatment with U73122 (10 microM) blocked the initiation of bursts of potential. Ruthenium red (100 microM) or caffeine (10 mM) facilitated the procaine-elicited bursts of potential. It is concluded that procaine reversibly elicits bursts of potential in the central snail neuron. This effect was not directly related to (1) the extra-cellular calcium ion fluxes, (2) the ryanodine sensitive calcium channels in the neuron, or (3) the PKC or PKA related messenger systems. The procaine-elicited bursts of potential were associated with the phospholipase activity and the calcium mobilization in the neuron.
Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim
2012-10-01
Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.
Kv1 channels and neural processing in vestibular calyx afferents.
Meredith, Frances L; Kirk, Matthew E; Rennie, Katherine J
2015-01-01
Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.
Hüllemann, P; von der Brelie, C; Manthey, G; Düsterhöft, J; Helmers, A K; Synowitz, M; Baron, R
2017-05-01
Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.e. painful radiculopathy. At the side of radiating pain, four blocks of 25 painful laser stimuli each were applied to the ventral thigh at the L3 dermatome in 27 patients with painful radiculopathy. Inclusion criteria were (1) at least one neurological finding of radiculopathy, (2) low back pain with radiation into the foot and (3) a positive one-sided compression of the L5 and/or S1 root in the MRI. The time course of LEP-habituation was compared to 20 healthy height and age matched controls. Signs of peripheral (heat hyperalgesia) and central sensitization (dynamic mechanical allodynia and hyperalgesia) at the affected L5 or S1 dermatome were assessed with quantitative sensory testing. Painful radiculopathy patients showed decreased LEP-habituation compared to controls. Patients with signs of central sensitization showed a more prominent LEP-habituation decrease within the radiculopathy patient group. Laser-evoked potential habituation is reduced in painful radiculopathy patients, which indicates an abnormal central pain processing. Central sensitization seems to be a major contributor to abnormal LEP habituation. The LEP habituation paradigm might be useful as a clinical tool to assess central pain processing alterations in nociceptive and neuropathic pain conditions. Abnormal central pain processing in neuropathic pain conditions may be revealed with the laser-evoked potential habituation paradigm. In painful radiculopathy patients, LEP-habituation is reduced compared to healthy controls. © 2017 European Pain Federation - EFIC®.
A geologic and morphological description of Ishtar terra (Venus)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sukhanov, A.L.; Kotel'nikov, V.A.; Ostrovskii, M.V.
The main part of Ishtar Terra east of Maxwell Montes is covered by systems of area dislocations in several directions that are called ''parquet.'' From the structural pictures, 1) a stable central block, 2) smaller peripheral blocks separated from the central block by faults and grabens, 3) zones of mobilized parquet, the matter of which spread down below the slope in a direction away from the central block in the form of plastic flows, and 4) partially ''parquetized'' lava rock masses are distinguished here. The Maxwell Montes were formed as the result of the collision of the central block andmore » the Lakshmi Planum.« less
DISTINCT FUNCTIONS OF JNK AND C-JUN IN OXIDANT-INDUCED HEPATOCYTE DEATH
Amir, Muhammad; Liu, Kun; Zhao, Enpeng; Czaja, Mark J.
2013-01-01
Overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling is a central mechanism of hepatocyte injury and death including that from oxidative stress. However, the functions of JNK and c-Jun are still unclear, and this pathway also inhibits hepatocyte death. Previous studies of menadione-induced oxidant stress demonstrated that toxicity resulted from sustained JNK/c-Jun activation as death was blocked by the c-Jun dominant negative TAM67. To further delineate the function of JNK/c-Jun signaling in hepatocyte injury from oxidant stress, the effects of direct JNK inhibition on menadione-induced death were examined. In contrast to the inhibitory effect of TAM67, pharmacological JNK inhibition by SP600125 sensitized the rat hepatocyte cell line RALA255-10G to death from menadione. SP600125 similarly sensitized mouse primary hepatocytes to menadione toxicity. Death from SP600125/menadione was c-Jun dependent as it was blocked by TAM67, but independent of c-Jun phosphorylation. Death occurred by apoptosis and necrosis and activation of the mitochondrial death pathway. Short hairpin RNA knockdowns of total JNK or JNK2 sensitized to death from menadione, whereas a jnk1 knockdown was protective. Jnk2 null mouse primary hepatocytes were also sensitized to menadione death. JNK inhibition magnified decreases in cellular ATP content and β-oxidation induced by menadione. This effect mediated cell death as chemical inhibition of β-oxidation also sensitized cells to death from menadione, and supplementation with the β-oxidation substrate oleate blocked death. Components of the JNK/c-Jun signaling pathway have opposing functions in hepatocyte oxidant stress with JNK2 mediating resistance to cell death and c-Jun promoting death. PMID:22644775
NASA Technical Reports Server (NTRS)
Sukhanov, A. L.; Pronin, A. A.; Tyuflin, Y. S.; Ostrovskiy, M. V.; Kotelnikov, V. A.; Rzhiga, O. N.; Petrov, G. I.; Sidorenko, A. I.; Aleksandrov, Y. N.; Zakharov, A. I.
1986-01-01
The main part of the Ishtar Terra east of the Maxwell Montes is covered with systems of areal dislocations of several directions, which are called Parquet. According to the structural patterns these may be divided into: (1) the central stable block; (2) the lesser peripheral blocks separated from the central one by gaps and grabens; (3) the zones of mobilized parquet, whose substance flowed downward at an incline in the directions away from the central block in the form of plastic flows; and (4) the partially parqueted lava sheets. The Maxwell Montes were formed as a result of the collision between the central parquet block and the Lakshmi Planum.
Monte Carlo Analysis of the Battery-Type High Temperature Gas Cooled Reactor
NASA Astrophysics Data System (ADS)
Grodzki, Marcin; Darnowski, Piotr; Niewiński, Grzegorz
2017-12-01
The paper presents a neutronic analysis of the battery-type 20 MWth high-temperature gas cooled reactor. The developed reactor model is based on the publicly available data being an `early design' variant of the U-battery. The investigated core is a battery type small modular reactor, graphite moderated, uranium fueled, prismatic, helium cooled high-temperature gas cooled reactor with graphite reflector. The two core alternative designs were investigated. The first has a central reflector and 30×4 prismatic fuel blocks and the second has no central reflector and 37×4 blocks. The SERPENT Monte Carlo reactor physics computer code, with ENDF and JEFF nuclear data libraries, was applied. Several nuclear design static criticality calculations were performed and compared with available reference results. The analysis covered the single assembly models and full core simulations for two geometry models: homogenous and heterogenous (explicit). A sensitivity analysis of the reflector graphite density was performed. An acceptable agreement between calculations and reference design was obtained. All calculations were performed for the fresh core state.
Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.
Jacob, S; Balletshofer, B; Henriksen, E J; Volk, A; Mehnert, B; Löblein, K; Häring, H U; Rett, K
1999-01-01
Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.
Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses
Paganelli, Meaghan A.
2015-01-01
NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775
Karmakar, M K; Li, X; Kwok, W H; Ho, A M-H; Ngan Kee, W D
2012-01-01
Objectives The use of ultrasound to guide peripheral nerve blocks is now a well-established technique in regional anaesthesia. However, despite reports of ultrasound guided epidural access via the paramedian approach, there are limited data on the use of ultrasound for central neuraxial blocks, which may be due to a poor understanding of spinal sonoanatomy. The aim of this study was to define the sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach. Methods The sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach was defined using a “water-based spine phantom”, young volunteers and anatomical slices rendered from the Visible Human Project data set. Results The water-based spine phantom was a simple model to study the sonoanatomy of the osseous elements of the lumbar spine. Each osseous element of the lumbar spine, in the spine phantom, produced a “signature pattern” on the paramedian sagittal scans, which was comparable to its sonographic appearance in vivo. In the volunteers, despite the narrow acoustic window, the ultrasound visibility of the neuraxial structures at the L3/L4 and L4/L5 lumbar intervertebral spaces was good, and we were able to delineate the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach. Conclusion Using a simple water-based spine phantom, volunteer scans and anatomical slices from the Visible Human Project (cadaver) we have described the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region. PMID:22010025
Forest statistics for west central Oregon.
John W. Hazard; Melvin E. Metcalf
1965-01-01
This publication summarizes the results of the latest reinventory of four counties centrally located in western Oregon: Benton, Lane, Lincoln, and Linn. This block of four counties is one of 10 such blocks set up in the States of Oregon and Washington by the Forest Survey to facilitate orderly reinventories of the timber resources. Each block will be reinventoried at...
Localized periorbital edema induced by aspirin.
Katz, Y; Goldberg, N; Kivity, S
1993-07-01
We documented localized periorbital edema in two patients with aspirin sensitivity without underlying chronic urticaria. The reaction developed 30 min after ingestion of 62.5 and 125 mg of aspirin, respectively. No systemic symptoms were observed. Other NSAIDs did not induce symptoms. These patients were able to tolerate doses of aspirin after pretreatment with terfenadine. These observations suggest that histamine plays a central role in aspirin-induced skin reaction. Despite the fact that terfenadine blocks the drug-induced reaction, this protocol should be used with caution and only where there is no feasible alternative to aspirin.
de Jonge, Maretha; Kemner, Chantal; Naber, Fabienne; van Engeland, Herman
2009-04-01
Superior performance on block design tasks is reported in autistic individuals, although it is not consistently found in high-functioning individuals or individuals with Asperger Syndrome. It is assumed to reflect weak central coherence: an underlying cognitive deficit, which might also be part of the genetic makeup of the disorder. We assessed block design reconstruction skills in high-functioning individuals with autism spectrum disorders (ASD) from multi-incidence families and in their parents. Performance was compared to relevant matched control groups. We used a task that was assumed to be highly sensitive to subtle performance differences. We did not find individuals with ASD to be significantly faster on this task than the matched control group, not even when the difference between reconstruction time of segmented and pre-segmented designs was compared. However, we found individuals with ASD to make fewer errors during the process of reconstruction which might indicate some dexterity in mental segmentation. However, parents of individuals with ASD did not perform better on the task than control parents. Therefore, based on our data, we conclude that mental segmentation ability as measured with a block design reconstruction task is not a neurocognitive marker or endophenotype useful in genetic studies.
Bowens, Clifford; Gupta, Rajnish K; O'Byrne, William T; Schildcrout, Jonathan S; Shi, Yaping; Hawkins, Jermel J; Michaels, Damon R; Berry, James M
2010-05-01
In this study, we performed the infraclavicular block with combined ultrasound guidance and neurostimulation to selectively target cords to compare the success rates of placing a single injection of local anesthetic either in a central or peripheral location. Two hundred eighteen patients were enrolled in a consecutive, prospective study. Patients were randomized to injection of local anesthetic either centrally (posterior cord) or peripherally (medial or lateral cord) using ultrasound guidance and neurostimulation. Supervised senior anesthesiology residents or attending anesthesiologists performed the blocks. Both intent-to-treat and treatment-received analyses were used to compare central and peripheral placement efficacy. The overall success rate was significantly higher for the central placements than peripheral placements (96% vs 85%, P = 0.004). Individual cord success rates were as follows: posterior 99%, lateral 92%, and medial 84% (P = 0.001). The central group required attending physician intervention more frequently (27% vs 6%, P < 0.001). Postoperative pain scores of < or =3 were more likely with central placement (100% vs 94%, P = 0.012). Central placement of a single injection of local anesthetic targeted at the posterior cord resulted in a higher success rate for infraclavicular block.
Kim, Hyun Jung; Ahn, Hyeong Sik; Lee, Jae Young; Choi, Seong Soo; Cheong, Yu Seon; Kwon, Koo; Yoon, Syn Hae
2017-01-01
Background Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed. PMID:28119767
DOE Office of Scientific and Technical Information (OSTI.GOV)
Determan, Michael Duane
The central theme of this thesis work is to develop new block copolymer materials for biomedical applications. While there are many reports of stimuli-responsive amphiphilic [19-21] and crosslinked hydrogel materials [22], the development of an in situ gel forming, pH responsive pentablock copolymer is a novel contribution to the field, Figure 1.1 is a sketch of an ABCBA pentablock copolymer. The A blocks are cationic tertiary amine methacrylates blocked to a central Pluronic F127 triblock copolymer. In addition to the prerequisite synthetic and macromolecular characterization of these new materials, the self-assembled supramolecular structures formed by the pentablock were experimentally evaluated.more » This synthesis and characterization process serves to elucidate the important structure property relationships of these novel materials, The pH and temperature responsive behavior of the pentablock copolymer were explored especially with consideration towards injectable drug delivery applications. Future synthesis work will focus on enhancing and tuning the cell specific targeting of DNA/pentablock copolymer polyplexes. The specific goals of this research are: (1) Develop a synthetic route for gel forming pentablock block copolymers with pH and temperature sensitive properties. Synthesis of these novel copolymers is accomplished with ATRP, yielding low polydispersity and control of the block copolymer architecture. Well defined macromolecular characteristics are required to tailor the phase behavior of these materials. (2) Characterize relationship between the size and shape of pentablock copolymer micelles and gel structure and the pH and temperature of the copolymer solutions with SAXS, SANS and CryoTEM. (3) Evaluate the temperature and pH induced phase separation and macroscopic self-assembly phenomenon of the pentablock copolymer. (4) Utilize the knowledge gained from first three goals to design and formulate drug delivery formulations based on the multi-responsive properties of the pentablock copolymer. Demonstrate potential biomedical applications of these materials with in vitro drug release studies from pentablock copolymer hydrogels. The intent of this work is to contribute to the knowledge necessary for further tailoring of these, and other functional block copolymer materials for biomedical applications.« less
Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa
2014-04-01
The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.
Huang, Yung-Jen; Lee, Kuan H; Grau, James W
2017-02-01
Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.
Kurien, Regi; Chrisolyte, Shipra; Rupa, V
2009-09-01
To assess eustachian tubal function (ETF) preoperatively in patients with chronic suppurative otitis media (CSOM) with central perforation by performing the inflation-deflation test. To correlate the results of the inflation-deflation test with the finding of aditus patency or block in patients with CSOM STUDY DESIGN: Prospective, cohort Tertiary care hospital Eighty adult patients with chronic suppurative otitis media and central perforation were recruited into the study. There were 45 males and 35 females. All patients underwent preoperative inflation-deflation test followed by cortical mastoidectomy and tympanoplasty. The patency of the aditus was assessed intraoperatively. Equalization of pressure on inflation-deflation test and intraoperative assessment of aditus patency Of a total of 80 patients, 49 patients were found to have discharging ears and 31 had dry ears at the time of surgery. In dry ears the inflation-deflation test had a sensitivity of 93% in predicting aditus patency although the specificity was lower at 67%. In discharging ears the sensitivity in predicting aditus patency was 72% and the specificity was 67%. The eustachian tube inflation-deflation test is a sensitive test for predicting aditus patency in patients with dry ears but less so in patients with discharging ears. Hence, it could be used in the former to avoid unnecessary exploration of the mastoid.
Central effects of humanin on hepatic triglyceride secretion.
Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H
2015-08-01
Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. Copyright © 2015 the American Physiological Society.
Diuretic‐sensitive electroneutral Na+ movement and temperature effects on central axons
Kanagaratnam, Meneka; Pendleton, Christopher; Souza, Danilo Almeida; Pettit, Joseph; Howells, James
2017-01-01
Key points Optic nerve axons get less excitable with warming.F‐fibre latency does not shorten at temperatures above 30°C.Action potential amplitude falls when the Na+‐pump is blocked, an effect speeded by warming.Diuretics reduce the rate of action potential fall in the presence of ouabain.Our data are consistent with electroneutral entry of Na+ occurring in axons and contributing to setting the resting potential. Abstract Raising the temperature of optic nerve from room temperature to near physiological has effects on the threshold, refractoriness and superexcitability of the shortest latency (fast, F) nerve fibres, consistent with hyperpolarization. The temperature dependence of peak impulse latency was weakened at temperatures above 30°C suggesting a temperature‐sensitive process that slows impulse propagation. The amplitude of the supramaximal compound action potential gets larger on warming, whereas in the presence of bumetanide and amiloride (blockers of electroneutral Na+ movement), the action potential amplitude consistently falls. This suggests a warming‐induced hyperpolarization that is reduced by blocking electroneutral Na+ movement. In the presence of ouabain, the action potential collapses. This collapse is speeded by warming, and exposure to bumetanide and amiloride slows the temperature‐dependent amplitude decline, consistent with a warming‐induced increase in electroneutral Na+ entry. Blocking electroneutral Na+ movement is predicted to be useful in the treatment of temperature‐dependent symptoms under conditions with reduced safety factor (Uhthoff's phenomenon) and provide a route to neuroprotection. PMID:28213919
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miller, Richard Dean; Thom, Robert Anthony
A light shielding apparatus for blocking light from reaching an electronic device, the light shielding apparatus including left and right support assemblies, a cross member, and an opaque shroud. The support assemblies each include primary support structure, a mounting element for removably connecting the apparatus to the electronic device, and a support member depending from the primary support structure for retaining the apparatus in an upright orientation. The cross member couples the left and right support assemblies together and spaces them apart according to the size and shape of the electronic device. The shroud may be removably and adjustably connectablemore » to the left and right support assemblies and configured to take a cylindrical dome shape so as to form a central space covered from above. The opaque shroud prevents light from entering the central space and contacting sensitive elements of the electronic device.« less
NASA Astrophysics Data System (ADS)
Bormann, Jayne M.; Hammond, William C.; Kreemer, Corné; Blewitt, Geoffrey
2016-04-01
We present 264 new interseismic GPS velocities from the Mobile Array of GPS for Nevada Transtension (MAGNET) and continuous GPS networks that measure Pacific-North American plate boundary deformation in the Central Walker Lane. Relative to a North America-fixed reference frame, northwestward velocities increase smoothly from ∼4 mm/yr in the Basin and Range province to 12.2 mm/yr in the central Sierra Nevada resulting in a Central Walker Lane deformation budget of ∼8 mm/yr. We use an elastic block model to estimate fault slip and block rotation rates and patterns of deformation from the GPS velocities. Right-lateral shear is distributed throughout the Central Walker Lane with strike-slip rates generally <1.5 mm/yr predicted by the block model, but extension rates are highest near north-striking normal faults found along the Sierra Nevada frontal fault system and in a left-stepping, en-echelon series of asymmetric basins that extend from Walker Lake to Lake Tahoe. Neotectonic studies in the western Central Walker Lane find little evidence of strike-slip or oblique faulting in the asymmetric basins, prompting the suggestion that dextral deformation in this region is accommodated through clockwise block rotations. We test this hypothesis and show that a model relying solely on the combination of clockwise block rotations and normal faulting to accommodate dextral transtensional strain accumulation systematically misfits the GPS data in comparison with our preferred model. This suggests that some component of oblique or partitioned right-lateral fault slip is needed to accommodate shear in the asymmetric basins of the western Central Walker Lane. Present-day clockwise vertical axis rotation rates in the Bodie Hills, Carson Domain, and Mina Deflection are between 1-4°/Myr, lower than published paleomagnetic rotation rates, suggesting that block rotation rates have decreased since the Late to Middle Miocene.
Cell block one and southeast guard tower, looking from the ...
Cell block one and southeast guard tower, looking from the central guard tower, facing southeast (note view also includes cell block ten (left) and cell block nine (right)) - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA
Rigano, K S; Gehring, J L; Evans Hutzenbiler, B D; Chen, A V; Nelson, O L; Vella, C A; Robbins, C T; Jansen, H T
2017-05-01
Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. We also used bear gluteal adipocyte cultures to test insulin and beta-adrenergic sensitivity in vitro. Bears were insulin resistant during hibernation but were sensitive during the spring and fall active periods. Hibernating bears remained euglycemic, possibly due to hyperinsulinemia and hyperglucagonemia. Adipokine concentrations were relatively low throughout the active season but peaked in mid-October prior to hibernation when fat content was greatest. Serum glycerol was highest during hibernation, indicating ongoing lipolysis. Centrally administered leptin reduced food intake in October, but not in August, revealing seasonal variation in the brain's sensitivity to its anorectic effects. This was supported by strong phosphorylated signal transducer and activator of transcription 3 labeling within the hypothalamus of hibernating bears; labeling virtually disappeared in active bears. Adipocytes collected during hibernation were insulin resistant when cultured with hibernation serum but became sensitive when cultured with active season serum. Heat treatment of active serum blocked much of this action. Clarifying the cellular mechanisms responsible for the physiology of hibernating bears may inform new treatments for metabolic disorders.
A dual-task investigation of automaticity in visual word processing
NASA Technical Reports Server (NTRS)
McCann, R. S.; Remington, R. W.; Van Selst, M.
2000-01-01
An analysis of activation models of visual word processing suggests that frequency-sensitive forms of lexical processing should proceed normally while unattended. This hypothesis was tested by having participants perform a speeded pitch discrimination task followed by lexical decisions or word naming. As the stimulus onset asynchrony between the tasks was reduced, lexical-decision and naming latencies increased dramatically. Word-frequency effects were additive with the increase, indicating that frequency-sensitive processing was subject to postponement while attention was devoted to the other task. Either (a) the same neural hardware shares responsibility for lexical processing and central stages of choice reaction time task processing and cannot perform both computations simultaneously, or (b) lexical processing is blocked in order to optimize performance on the pitch discrimination task. Either way, word processing is not as automatic as activation models suggest.
Hungen, K V; Roberts, S; Hill, D F
1975-08-22
Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and, in relatively high concentration (100 muM), partially blocked the activation by 10 muM dopamine, but was without effect on the stimulation by 10 muM D-LSD. The present results indicate that serotonin antagonists, in general, are potent inhibitors of catecholamine-induced stimulation of adenylate cyclase systems in brain cell-free preparations. In addition, these results, coupled with earlier findings on the capacity of D-LSD to interact with serotonin-sensitive adenylate cyclase systems from rat brain23,24 and other neural systems16, strongly suggest that this hallucinogenic agent is capable of acting as an agonist at central dopamine and serotonin receptors, as well as functioning as an antagonist at dopamine, norepinephrine, and serotonin receptors in the brain.
A Lower-Cost High-Resolution LYSO Detector Development for Positron Emission Mammography (PEM)
Ramirez, Rocio A.; Zhang, Yuxuan; Liu, Shitao; Li, Hongdi; Baghaei, Hossain; An, Shaohui; Wang, Chao; Jan, Meei-Ling; Wong, Wai-Hoi
2010-01-01
In photomultiplier-quadrant-sharing (PQS) geometry for positron emission tomography applications, each PMT is shared by four blocks and each detector block is optically coupled to four round PMTs. Although this design reduces the cost of high-resolution PET systems, when the camera consists of detector panels that are made up of square blocks, half of the PMT’s sensitive window remains unused at the detector panel edge. Our goal was to develop a LYSO detector panel which minimizes the unused portion of the PMTs for a low-cost, high-resolution, and high-sensitivity positron emission mammography (PEM) camera. We modified the PQS design by using elongated blocks at panel edges and square blocks in the inner area. For elongated blocks, symmetric and asymmetrical reflector patterns were developed and PQS and PMT-half-sharing (PHS) arrangements were implemented in order to obtain a suitable decoding. The packing fraction was 96.3% for asymmetric block and 95.5% for symmetric block. Both of the blocks have excellent decoding capability with all crystals clearly identified, 156 for asymmetric and 144 for symmetric and peak-to-valley ratio of 3.0 and 2.3 respectively. The average energy resolution was 14.2% for the asymmetric block and 13.1% for the symmetric block. Using a modified PQS geometry and asymmetric block design, we reduced the unused PMT region at detector panel edges, thereby increased the field-of-view and the overall detection sensitivity and minimized the undetected breast region near the chest wall. This detector design and using regular round PMT allowed building a lower-cost, high-resolution and high-sensitivity PEM camera. PMID:20485510
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-21
... DEPARTMENT OF THE INTERIOR Central Utah Project Completion Act: Availability of Draft Environmental Assessment; Block Notice 1A, Heber Sub-Area Irrigation to M&I Water Conversion, Wasatch County, UT AGENCY: Department of the Interior, Office of the Assistant Secretary-- Water and Science. ACTION: Notice...
47 CFR 52.20 - Thousands-block number pooling.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 3 2013-10-01 2013-10-01 false Thousands-block number pooling. 52.20 Section... (CONTINUED) NUMBERING Number Portability § 52.20 Thousands-block number pooling. (a) Definition. Thousands-block number pooling is a process by which the 10,000 numbers in a central office code (NXX) are...
Timber resource statistics for central Oregon.
John M. Berger
1968-01-01
This publication summarizes the results of the third inventory of the timber resources of nine counties in central Oregon: Crook, Deschutes, Gilliam, Jefferson, Klamath, Lake, Sherman, Wasco, and Wheeler. This block of nine counties is one of 10 such blocks set up in the States of Oregon and Washington by the Forest Survey to facilitate orderly reinventories of the...
Wnt addiction of genetically defined cancers reversed by PORCN inhibition.
Madan, B; Ke, Z; Harmston, N; Ho, S Y; Frois, A O; Alam, J; Jeyaraj, D A; Pendharkar, V; Ghosh, K; Virshup, I H; Manoharan, V; Ong, E H Q; Sangthongpitag, K; Hill, J; Petretto, E; Keller, T H; Lee, M A; Matter, A; Virshup, D M
2016-04-28
Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.
Lai, H; Carino, M A
1992-07-01
Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.
Lee, Younglim; Pai, Madhavi; Brederson, Jill-Desiree; Wilcox, Denise; Hsieh, Gin; Jarvis, Michael F; Bitner, Robert S
2011-05-20
Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA) pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vogel, S.S.
1989-01-01
The author has characterized pertussis toxin-sensitive G proteins in the nervous systems of the gastropod mollusc Aplysia and the cephalopod Loligo using ({sup 32}P)ADP-ribosylation and immunoblotting with G protein specific antisera. As in vertebrates, this class of G protein is associated with membranes and enriched in nervous tissue in Aplysia. Analysis of dissected Aplysia ganglia reveal that it is enriched in neuropil, a region containing most of the central nervous system synapses. Because both Aplysia and Loligo synaptosomes are enriched in pertussis toxin-sensitive G proteins, it is likely that they are found in synaptic terminals. Fractionation of Aplysia synaptosomes intomore » membrane and vesicle fractions reveals that, although the majority of G protein is recovered in the plasma membrane fraction, a small proportion is recovered in the vesicle fraction. He shows that G proteins are on intracellular membranes by ADP-ribosylating extruded axoplasm with pertussis toxin. A plausible explanation for vesicular localization of G protein in axoplasm is that G proteins are transported to terminals on vesicles. He has shown, using ligature experiments with Aplysia connectives and temperature block experiments in the giant axon of Loligo, that G proteins move by anterograde fast axonal transport. Injection of pertussis toxin into the identified Aplysia neuron L10 blocks histamine-induced presynaptic inhibition of transmitter release. This suggests that pertussis toxin sensitive G proteins play a role in modulating transmitter release at synaptic terminals. In the giant synapse of Loligo, he presents preliminary data that demonstrates that the activation of G proteins in the presynaptic terminal results in decreased transmitter release.« less
Tip/tilt optimizations for polynomial apodized vortex coronagraphs on obscured telescope pupils
NASA Astrophysics Data System (ADS)
Fogarty, Kevin; Pueyo, Laurent; Mazoyer, Johan; N'Diaye, Mamadou
2017-09-01
Obstructions due to large secondary mirrors, primary mirror segmentation, and secondary mirror support struts all introduce diffraction artifacts that limit the performance offered by coronagraphs. However, just as vortex coronagraphs provides theoretically ideal cancellation of on-axis starlight for clear apertures, the Polynomial Apodized Vortex Coronagraph (PAVC) completely blocks on-axis light for apertures with central obscurations, and delivers off-axis throughput that improves as the topological charge of the vortex increases. We examine the sensitivity of PAVC designs to tip/tilt aberrations and stellar angular size, and discuss methods for mitigating these effects. By imposing additional constraints on the pupil plane apodization, we decrease the sensitivity of the PAVC to the small positional shifts of the on-axis source induced by either tip/tilt or stellar angular size; providing a route to overcoming an important hurdle facing the performance of vortex coronagraphs on telescopes with complicated pupils.
Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe
2017-01-01
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941
Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe
2017-10-17
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.
Effects of Cocos Ridge Collision on the Western Caribbean: Is there a Panama Block?
NASA Astrophysics Data System (ADS)
Kobayashi, D.; La Femina, P. C.; Geirsson, H.; Chichaco, E.; Abrego M, A. A.; Fisher, D. M.; Camacho, E. I.
2011-12-01
It has been recognized that the subduction and collision of the Cocos Ridge, a 2 km high aseismic ridge standing on >20 km thick oceanic crust of the Cocos plate, drives upper plate deformation in southern Central America. Recent studies of Global Positioning System (GPS) derived horizontal velocities relative to the Caribbean Plate showed a radial pattern centered on the Cocos Ridge axis where Cocos-Caribbean convergence is orthogonal, and margin-parallel velocities to the northwest. Models of the full three-dimensional GPS velocity field and earthquake slip vectors demonstrate low mechanical coupling along the Middle America subduction zone in Nicaragua and El Salvador, and a broad zone of high coupling beneath the Osa Peninsula, where the Cocos Ridge intersects the margin. These results suggest that Cocos Ridge collision may be the main driver for trench-parallel motion of the fore arc to the northwest and for uplift and shortening of the outer fore arc in southern Central America, whereby thickened and hence buoyant Cocos Ridge crust acts as an indenter causing the tectonic escape of the fore arc. These studies, however, were not able to constrain well the pattern of surface deformation east-southeast of the ridge axis due to a lack of GPS stations, and Cocos Ridge collision may be responsible for the kinematics and deformation of the proposed Panama block. Recent reinforcement of the GPS network in southeastern Costa Rica and Panama has increased the spatial and temporal resolution of the network and made it possible to further investigate surface deformation of southern Central America and the Panama block. We present a new regional surface velocity field for Central America from geodetic GPS data collected at 11 recently-installed and 178 existing episodic, semi-continuous, and continuous GPS sites in Nicaragua, Costa Rica, and Panama. We investigate the effects of Cocos Ridge collision on the Panama block through kinematic block modeling. Published earthquake relocation and geologic data are used to define block boundaries and fault geometries. We invert the three-dimensional GPS velocity vectors and earthquake slip vectors to estimate the magnitude and spatial distribution of interplate mechanical coupling on active plate and block boundaries around the Panama block; the Middle America Trench - South Panama Deformed Belt, the Central Costa Rican Deformed Belt, and the North Panama Deformed Belt in particular, and the rates of relative plate motion between the Panama block and the adjacent Cocos, Nazca, and Caribbean plates. This study tests whether the Panama block responds to the ridge collision as a rigid tectonic block or as a deforming zone consisting of multiple blocks.
Blocks as a Tool for Learning: Historical and Contemporary Perspectives.
ERIC Educational Resources Information Center
Hewitt, Karen
2001-01-01
Examines the central historical and contemporary role of blocks and construction toys in early childhood education. Describes how commercially produced blocks were conceptualized as a surface for displaying symbols, as pure form, or as a way to transmit a cultural heritage of architectural styles. Discusses how blocks were used in early…
The Crustal and Mantle Velocity Structure in Central Asia from 3D Travel Time Tomography
2010-09-01
the Turan plate, and the Tarim block. This geologically and tectonically complicated area is also one of the most seismically active regions in the...Asia features large blocks such as the Indian plate, the Afghan block, the Turan plate, and the Tarim block. This geologically and tectonically
Linking atmospheric blocking to European temperature extremes in spring
NASA Astrophysics Data System (ADS)
Brunner, Lukas; Hegerl, Gabriele; Steiner, Andrea
2017-04-01
The weather in Europe is influenced by a range of dynamical features such as the Atlantic storm tracks, the jet stream, and atmospheric blocking. Blocking describes an atmospheric situation in which a stationary and persistent high pressure system interrupts the climatological flow for several days to weeks. It can trigger cold and warm spells which is of special relevance during the spring season because vegetation is particularly vulnerable to extreme temperatures in the early greening phase. We investigate European cold and warm spells in the 36 springs from 1979 to 2014 in temperature data from the European daily high-resolution gridded dataset (E-OBS) and connect them to blocking derived from geopotential height fields from ERA-Interim. A highly significant link between blocking and both, cold and warm spells is found that changes during spring. Resolving monthly frequencies, we find a shift in the preferred locations of blocking throughout spring. The maximum blocking frequency during cold spells shifts from Scandinavia to the British Isles in March and April. During warm spells it continuously shifts further northward during the spring season. The location of the block is found to be essential for the sign of the relationship. Blocking over the north-eastern Atlantic and over northern Europe is strongly linked to cold conditions, while blocking over central Europe is associated with warm conditions. Consistently the spatial distribution of temperature extremes across Europe is highly sensitive to the occurrence of blocking. More than 80 % of cold spells in south-eastern Europe occur during blocking, compared to less than 30 % in northern Europe. Warm spells show the opposite pattern and more than 70 % co-occur with blocking in northern Europe, compared to less than 30 % in parts of southern Europe. We find considerable interannual variability over the analysis period from 1979 to 2014 but also a decrease in cold spells and an increase in warm spells, especially in the last 15 years, indicating the influence of global warming. The change to a warmer environment holds the potential for even higher vulnerability to cold extremes, which can be triggered by blocking in late spring. Brunner, L., G. Hegerl, and A. Steiner, 2017: Connecting Atmospheric Blocking to European Temperature Extremes in Spring. J. Climate, 30, 585-594, doi: 10.1175/JCLI-D-16-0518.1.
Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara
2016-03-01
Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Steffen, Holger; Wu, Patrick
2015-04-01
This poster will present the results of Steffen & Wu (2014). The sensitivity of GNSS measurements in Fennoscandia to nearby viscosity variations in the upper mantle is investigated using a three-dimensional finite element model of glacial isostatic adjustment (GIA). Based on the lateral viscosity structure inferred from seismic tomography and the location of the ice margin at the last glacial maximum (LGM), the GIA earth model is subdivided into four layers, where each of them contains an amalgamation of about 20 blocks of different shapes in the central area. The sensitivity kernels of the three velocity components at 10 selected GNSS stations are then computed for all the blocks. We find that GNSS stations within the formerly glaciated area are most sensitive to mantle viscosities below and in its near proximity, i.e., within about 250 km in general. However, this can be as large as 1000 km if the stations lie near the center of uplift. The sensitivity of all stations to regions outside the ice margin during the LGM is generally negligible. In addition, it is shown that prominent structures in the second (250-450 km depth) and third layers (450-550 km depth) of the upper mantle may be readily detected by GNSS measurements, while the viscosity in the first mantle layer below the lithosphere (70-250 km depth) along the Norwegian coast, which is related to lateral lithospheric thickness variation there, can also be detected but with limited sensitivity. For future investigations on the lateral viscosity structure, preference should be on GNSS stations within the LGM ice margin. But these stations can be grouped into clusters to improve the inference of viscosity in a specific area. However, the GNSS measurements used in such inversion should be weighted according to their sensitivity. Such weighting should also be applied when they are used in combination with other GIA data (e.g., relative sea-level and gravity data) for the inference of mantle viscosity. Reference: Steffen, H. and Wu, P.: The sensitivity of GNSS measurements in Fennoscandia to distinct three-dimensional upper-mantle structures, Solid Earth, 5, 557-567, doi:10.5194/se-5-557-2014, 2014.
Cortical sources of ERP in prosaccade and antisaccade eye movements using realistic source models
Richards, John E.
2013-01-01
The cortical sources of event-related-potentials (ERP) using realistic source models were examined in a prosaccade and antisaccade procedure. College-age participants were presented with a preparatory interval and a target that indicated the direction of the eye movement that was to be made. In some blocks a cue was given in the peripheral location where the target was to be presented and in other blocks no cue was given. In Experiment 1 the prosaccade and antisaccade trials were presented randomly within a block; in Experiment 2 procedures were compared in which either prosaccade and antisaccade trials were mixed in the same block, or trials were presented in separate blocks with only one type of eye movement. There was a central negative slow wave occurring prior to the target, a slow positive wave over the parietal scalp prior to the saccade, and a parietal spike potential immediately prior to saccade onset. Cortical source analysis of these ERP components showed a common set of sources in the ventral anterior cingulate and orbital frontal gyrus for the presaccadic positive slow wave and the spike potential. In Experiment 2 the same cued- and non-cued blocks were used, but prosaccade and antisaccade trials were presented in separate blocks. This resulted in a smaller difference in reaction time between prosaccade and antisaccade trials. Unlike the first experiment, the central negative slow wave was larger on antisaccade than on prosaccade trials, and this effect on the ERP component had its cortical source primarily in the parietal and mid-central cortical areas contralateral to the direction of the eye movement. These results suggest that blocked prosaccade and antisaccade trials results in preparatory or set effects that decreases reaction time, eliminates some cueing effects, and is based on contralateral parietal-central brain areas. PMID:23847476
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lockwood, Jr., Neil; McLellan, Jason G; Crossley, Brian
The Resident Fish Stock Status above Chief Joseph and Grand Coulee Dams Project, commonly known as the Joint Stock Assessment Project (JSAP) is a management tool using ecosystem principles to manage artificial fish assemblages and native fish in altered environments existing in the Columbia River System above Chief Joseph and Grand Coulee Dams (blocked area). The three-phase approach of this project will enhance the fisheries resources of the blocked area by identifying data gaps, filling data gaps with research, and implementing management recommendations based on research results. The Blocked Area fisheries information housed in a central location will allow managersmore » to view the entire system while making decisions, rather than basing management decisions on isolated portions of the system. The JSAP (NWPPC program measure 10.8B.26) is designed and guided jointly by fisheries managers in the blocked area and the Columbia Basin blocked area management plan (1998). The initial year of the project (1997) identified the need for a central data storage and analysis facility, coordination with the StreamNet project, compilation of blocked area fisheries information, and a report on the ecological condition of the Spokane River System. These needs were addressed in 1998 by acquiring a central location with a data storage and analysis system, coordinating a pilot project with StreamNet, compiling fisheries distribution data throughout the blocked area, identifying data gaps based on compiled information, and researching the ecological condition of the Spokane River. In order to ensure that any additional information collected throughout the life of this project will be easily stored and manipulated by the central storage facility, it was necessary to develop standardized methodologies between the JSAP fisheries managers. The use of common collection and analytical tools is essential to the process of streamlining joint management decisions. In 1999 and 2000 the project began to address some of the identified data gaps, throughout the blocked area, with a variety of newly developed sampling projects, as well as, continuing with ongoing data collection of established projects.« less
Virasoro conformal blocks and thermality from classical background fields
Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.
2015-11-30
We show that in 2d CFTs at large central charge, the coupling of the stress tensor to heavy operators can be re-absorbed by placing the CFT in a non-trivial background metric. This leads to a more precise computation of the Virasoro conformal blocks between heavy and light operators, which are shown to be equivalent to global conformal blocks evaluated in the new background. We also generalize to the case where the operators carry U(1) charges. The refined Virasoro blocks can be used as the seed for a new Virasoro block recursion relation expanded in the heavy-light limit. Furthermore, we commentmore » on the implications of our results for the universality of black hole thermality in AdS 3 , or equivalently, the eigenstate thermalization hypothesis for CFT 2 at large central charge.« less
A Neurophysiological examination of quality of learning in a feedback-based learning task.
Arbel, Yael; Wu, Hao
2016-12-01
The efficiency with which one processes external feedback contributes to the speed and quality of one's learning. Previous findings that the feedback related negativity (FRN) event related potential (ERP) is modulated by learning outcomes suggested that this ERP reflects the extent to which feedback is used by the learner to improve performance. To further test this suggestion, we measured whether the FRN and the fronto-central positivity (FCP) that follows it are modulated by learning slopes, and as a function of individual differences in learning outcomes. Participants were tasked with learning names (non-words) of 42 novel objects in a two-choice feedback-based visual learning task. The items were divided into three sets of 14 items, each presented in five learning blocks and a sixth test block. Individual learning slopes based on performance on the task, as well as FRN and FCP slopes based on positive and negative feedback related activation in each block were created for 53 participants. Our data pointed to an interaction between slopes of the FRN elicited by negative feedback and learning slopes, such that a sharper decrease in the amplitude of the FRN to negative feedback was associated with sharper learning slopes. We further examined the predictive power of the FRN and FCP elicited in the training blocks on the learning outcomes as measured by performance on the test blocks. We found that small FRN to negative feedback, large FRN to positive feedback, and large FCP to negative feedback in the first training block predicted better learning outcomes. These results add to the growing evidence that the processes giving rise to the FRN and FCP are sensitive to individual differences in the extent to which feedback is used for learning. Copyright © 2016 Elsevier Ltd. All rights reserved.
Cattaneo, Ruggero; Marci, Maria Chiara; Pietropaoli, Davide; Ortu, Eleonora
2017-01-01
Dysregulation of Autonomic Nervous System (ANS) and central pain pathways in temporomandibular disorders (TMD) is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS), a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI) is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s) affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS) is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD) are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a) TMD with Central Sensitization ULFTENS Responders; (b) TMD with Central Sensitization ULFTENS Nonresponders; (c) TMD without Central Sensitization ULFTENS Responders; (d) TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology. PMID:28932132
NASA Astrophysics Data System (ADS)
Gourley, Jonathan R.; Byrne, Timothy; Chan, Yu-Chang; Wu, Francis; Rau, Ruey-Juin
2007-12-01
Data sets of collapsed earthquake locations, earthquake focal mechanisms, GPS velocities and geologic data are integrated to constrain the geometry and kinematics of a crustal block within the accreted continental margin rocks of Taiwan's northeastern Central Range. This block is laterally extruding and exhuming towards the north-northeast. The block is bound on the west-southwest by the previously recognized Sanyi-Puli seismic zone and on the east by a vertical seismic structure that projects to the eastern mountain front of the Central Range. Focal mechanisms from the Broadband Array of Taiwan Seismicity (BATS) catalog consistently show west-side-up reverse displacements for this fault zone. A second vertical structure is recognized beneath the Slate Belt-Metamorphic Belt boundary as a post-Chi-Chi relaxation oblique normal fault. BATS focal mechanisms show east-side-up, normal displacements with a minor left-lateral component. The vertical and lateral extrusion of this crustal block may be driven by the current collision between the Philippine Sea Plate and the Puli basement high indenter on the Eurasian Plate and/or trench rollback along the Ryukyu subduction zone. In addition, the vertical extent of the two shear zones suggests that a basal décollement below the eastern Central Range is deeper than previously proposed and may extend below the brittle-ductile transition.
NASA Astrophysics Data System (ADS)
Zhao, Dezheng; Qu, Chunyan; Shan, Xinjian; Zuo, Ronghu; Liu, Yunhua; Gong, Wenyu; Zhang, Guohong
2018-04-01
We have generated a more than 500 km long postseismic deformation rate map and cumulative displacement time series in the central Bayankala Block of the Tibetan Plateau using ENVISAT/ASAR data from 2003 to 2010 by the π-RATE stacking algorithm. This rate map spans a period of ∼7.2 years and reveals that postseismic motion of 2001 Kokoxili earthquake exhibits a striking signal, dominating crustal deformation of the central Bayankala Block with a cross-fault magnitude ∼9-11 mm/yr in line of sight (LOS) (∼93.1°E). The southern and northern parts of the postseismic deformation field exhibit different patterns and variable magnitudes, reflecting asymmetry of the displacement distribution. Postseismic motion affects eastward extrusion of the central Bayankala Block, which reaches ∼15 km north of the Ganzi-Yushu fault. To further investigate viscoelastic relaxation of the lower crust in this area after approximately two years, E-M, E-M-M and E-S models are constructed. The result shows that the best fit viscosity for the lower crust is about 1 × 1019 Pa·s. Comparison between cumulative displacements resolved by these three models shows that viscoelastic relaxation of the lower crust makes the most significant contribution to postseismic stress relaxation after 2001 event.
Kato, Jitsu; Gokan, Dai; Hirose, Noriya; Iida, Ryoji; Suzuki, Takahiro; Ogawa, Setsuro
2013-02-01
The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS. Wiley Periodicals, Inc.
Fabrics Protect Sensitive Skin from UV Rays
NASA Technical Reports Server (NTRS)
2009-01-01
Late Johnson Space Center engineer Dr. Robert Dotts headed a team to develop cool suits for children suffering from life-threatening sun sensitivities. Dotts hoped to develop ultraviolet-blocking technology in a fabric that -- unlike in a bulky space suit -- could remain comfortable, light, and breathable in the sun and heat. The team worked with SPF 4 US LLC (SPF) of Madison, Wisconsin to design ultraviolet-blocking cool suits, which protect sun-sensitive patients and enable them to experience life outdoors safely. Using knowledge gained during the NASA collaboration, SPF created an entire line of ultraviolet-blocking apparel.
Xu, Zifeng; Zhang, Jianhai; Xia, Yunfei; Deng, Xiaoming
2014-01-01
To observe the change of PVI after thoracic epidural block on the basis of general anesthesia. In 26 patients undergoing elective upper abdominal operations, changes of SVI, PVI, SVV, PPV and CVP were monitored immediately before and 10 minutes after T8-9 thoracic epidural anesthesia on the basis of general anesthesia. The definition was that patients with ΔSVI greater than 10% belonged to response group to epidural block. Before epidural block, the PVI, SVV and PPV baseline values in patients of response group were significantly higher than those in patients of non-response group. PVI, SVV and PPV after epidural block were significantly higher than immediately before epidural block (P < 0.001). PVI, SVV and PPV baseline values immediately before epidural block were positively correlated with ΔSVI; the correlation coefficients were 0.70, 0.71 and 0.63, respectively, P ≤ 0.001. The optimal critical values for PVI, SVV and PPV to predict response to T8-9 gap epidural block under general anesthesia were 16% (sensitivity 80%, specificity 92%), 13% (sensitivity 90%, specificity 62%) and 12% (sensitivity 90%, specificity 77%), respectively. PVI can be used as a noninvasive indictor to monitor volume change after thoracic epidural block on the basis of general anesthesia.
Central Venous Catheter (Central Line)
... the skin entry site. With care, central venous catheters can remain in the body for several months without becoming infected. ■ ■ Blocking or kinking— Blood clots may begin to form in the catheter but ...
Takemoto, Yumi
2014-12-01
The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors. The present study investigated cardiovascular responses to L-cysteine and L-ap4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of L-cysteine and L-AP4 in the CVLM sites identified with L-glutamate produced the same depressor and bradycardic responses in urethane-anesthetized rats. Neither a prior antagonist microinjection of MK801 for the N-methyl-D-aspartate (NMDA) receptor nor CNQX for the non-NMDA receptor attenuated the responses to L-cysteine, but the combination of the two receptor blocking with an additional prior injection abolished the response. In contrast, either receptor blockade alone abolished the response to L-AP4, indicating distinct mechanisms between responses to L-cysteine and L-AP4 in the CVLM. The results indicate that the CVLM is a central active site for L-cysteine's cardiovascular response. Central L-cysteine's action could be independent of the L-AP4 sensitive receptors. Cardiovascular regulation may involve endogenous L-cysteine in the CVLM. Further multidisciplinary examinations are required to elaborate on L-cysteine's functional roles in the CVLM. Copyright © 2014 Elsevier B.V. All rights reserved.
The sympathetic hazards of airborne ultrasound on ultrasound sensitive mice.
Ohmori, M; Ogawa, K
1982-01-01
A commercially available ultrasonic equipment (55-50 kHz/sec, 425 W) operated at a distance of 4 m air space caused death in some mice. The physical energy propagated was quite small, being calculated at less than 0.21 W/cm2. Among many strains of mice, the RIII strain was especially sensitive to ultrasound, and the peak of sensitivity was at 3 to 4 weeks of age at which the mortality rate was 95/149 (64%). No death occurred when mice were pretreated by (a) removing all body hair, (b) by administration of morphine hydrochloridum with a tail reaction, and (c) administration of a sympathetic blocking agent. From these results it is assumed that the ultrasound energy absorbed by the body fur reaches the hypothalamus through the sensory nerves of the hair roots. After the hypothalamus where central sympathetic nerve functions are localized, the stimulus passes down the descending tract of the sympathetic nerve, reaching the cardiac nerves via the autonomic nerve ganglion. Thus, death could occur by shock of the sympathetic nerve reflex.
Bus bar electrical feedthrough for electrorefiner system
Williamson, Mark; Wiedmeyer, Stanley G; Willit, James L; Barnes, Laurel A; Blaskovitz, Robert J
2013-12-03
A bus bar electrical feedthrough for an electrorefiner system may include a retaining plate, electrical isolator, and/or contact block. The retaining plate may include a central opening. The electrical isolator may include a top portion, a base portion, and a slot extending through the top and base portions. The top portion of the electrical isolator may be configured to extend through the central opening of the retaining plate. The contact block may include an upper section, a lower section, and a ridge separating the upper and lower sections. The upper section of the contact block may be configured to extend through the slot of the electrical isolator and the central opening of the retaining plate. Accordingly, relatively high electrical currents may be transferred into a glovebox or hot-cell facility at a relatively low cost and higher amperage capacity without sacrificing atmosphere integrity.
Rolling blackout is required for synaptic vesicle exocytosis.
Huang, Fu-De; Woodruff, Elvin; Mohrmann, Ralf; Broadie, Kendal
2006-03-01
Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate-diacylglycerol signaling in Drosophila neurons. Conditional temperature-sensitive (TS) rbo mutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, and rbo TS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adult rbo TS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction between rbo and syntaxin1A TS mutants, suggesting that RBO is required in the mechanism of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. The rbo TS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schiemann, Reinhard; Demory, Marie-Estelle; Shaffrey, Len C.
The aim of this study is to investigate if the representation of Northern Hemisphere blocking is sensitive to resolution in current-generation atmospheric global circulation models (AGCMs). An evaluation is thus conducted of how well atmospheric blocking is represented in four AGCMs whose horizontal resolution is increased from a grid spacing of more than 100 km to about 25 km. It is shown that Euro-Atlantic blocking is simulated overall more credibly at higher resolution (i.e., in better agreement with a 50-yr reference blocking climatology created from the reanalyses ERA-40 and ERA-Interim). The improvement seen with resolution depends on the season andmore » to some extent on the model considered. Euro-Atlantic blocking is simulated more realistically at higher resolution in winter, spring, and autumn, and robustly so across the model ensemble. The improvement in spring is larger than that in winter and autumn. Summer blocking is found to be better simulated at higher resolution by one model only, with little change seen in the other three models. The representation of Pacific blocking is not found to systematically depend on resolution. Despite the improvements seen with resolution, the 25-km models still exhibit large biases in Euro-Atlantic blocking. For example, three of the four 25-km models underestimate winter northern European blocking frequency by about one-third. The resolution sensitivity and biases in the simulated blocking are shown to be in part associated with the mean-state biases in the models' midlatitude circulation.« less
Schiemann, Reinhard; Demory, Marie-Estelle; Shaffrey, Len C.; ...
2016-12-19
The aim of this study is to investigate if the representation of Northern Hemisphere blocking is sensitive to resolution in current-generation atmospheric global circulation models (AGCMs). An evaluation is thus conducted of how well atmospheric blocking is represented in four AGCMs whose horizontal resolution is increased from a grid spacing of more than 100 km to about 25 km. It is shown that Euro-Atlantic blocking is simulated overall more credibly at higher resolution (i.e., in better agreement with a 50-yr reference blocking climatology created from the reanalyses ERA-40 and ERA-Interim). The improvement seen with resolution depends on the season andmore » to some extent on the model considered. Euro-Atlantic blocking is simulated more realistically at higher resolution in winter, spring, and autumn, and robustly so across the model ensemble. The improvement in spring is larger than that in winter and autumn. Summer blocking is found to be better simulated at higher resolution by one model only, with little change seen in the other three models. The representation of Pacific blocking is not found to systematically depend on resolution. Despite the improvements seen with resolution, the 25-km models still exhibit large biases in Euro-Atlantic blocking. For example, three of the four 25-km models underestimate winter northern European blocking frequency by about one-third. The resolution sensitivity and biases in the simulated blocking are shown to be in part associated with the mean-state biases in the models' midlatitude circulation.« less
NASA Astrophysics Data System (ADS)
Cao, Yong; Sun, Zhiming; Li, Haibing; Pei, Junling; Xu, Wei; Pan, Jiawei; Zhang, Lei; Ye, Xiaozhou; Huang, Baochun; Wang, Zongxiu
2017-10-01
There is an ongoing debate regarding the paleogeographic evolution of the Qaidam Block (37.3 °N/96.4 °E) in northwest China during the late Paleozoic. To provide a reliable constraint on the paleogeographic reconstruction and to determine the relationship with the adjacent area, we performed a paleomagnetic investigation of Early and Late Carboniferous sediments from the Qaidam Block. Stepwise thermal demagnetization successfully isolated high unblocking-temperature characteristic directions from the samples. The tilt-corrected mean direction of the Early Carboniferous sediments is Ds/Is = 298.6°/- 46.4° with α95 = 4.7° and N = 15 sites, corresponding to a paleopole at - 3.2 °N, 147.5 °E with A95 = 4.8°. The Late Carboniferous paleomagnetic direction is Ds/Is = 320.1°/- 46.1° with α95 = 5.3° and N = 8 sites, corresponding to a paleopole at - 15.1 °N, 132.2 °E with A95 = 5.4°. A positive fold test for the Early Carboniferous paleomagnetic directions, and consistency with the Kiaman reversed superchron for the Late Carboniferous paleomagnetic directions, indicates the primary origin of the characteristic remanence of the studied section. The new paleomagnetic results suggest that the Qaidam Block was located at about 27 °N and did not undergo significant N-S movement during the Carboniferous. However, the Qaidam Block experienced a counter-clockwise rotation of about 21° during this period. Comparisons of the paleomagnetic results from the major blocks of Central Asia suggest that the Qaidam Block may have experienced a relatively rapid northward movement and collided with the Tarim Block after the Late Permian. Based on the paleomagnetic poles of the Qaidam Block and adjacent blocks, we present a tentative paleogeographic reconstruction for central Asia during the Early and Late Carboniferous.
Grémeau-Richard, Christelle; Dubray, Claude; Aublet-Cuvelier, Bruno; Ughetto, Sylvie; Woda, Alain
2010-04-01
Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature the main location of which, peripheral or central, remains unknown. A randomised, double-blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam, the patient's response to a psychological questionnaire, and the taste and heat thresholds. The spontaneous burning was measured with a visual analogue scale (VAS) just before and 15 min after injection. The decreases in VAS score after lidocaine or saline injection were not significantly different (2.7+/-3.9 and 2.0+/-2.6, respectively; n=20). However, two groups of patients could be identified: in a "peripheral group" (n=10) the VAS decrease due to lingual nerve injection was 4.3+/-3.1cm after lidocaine and 0.9+/-0.3 cm after saline (p=0.02). In a "central group" (n=7), there were an increase in pain intensity score (-0.8+/-2.6 cm) after lidocaine and a decrease (1.5+/-3.0 cm) after saline (p=0.15). An increase in the hospital anxiety and depression (HAD) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age-and-sex-matched controls (p<0.05). Topical clonazepam treatment tended to be more effective (p=0.07) and HAD score lower (p<0.03) in the peripheral than in the central group. These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral, central or mixed depending on the individual. Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Geophysical characterization of the Chicxulub impact structure
NASA Astrophysics Data System (ADS)
Gulick, S. P.; Christeson, G. L.; Barton, P. J.; Grieve, R. A.; Morgan, J. V.; Fucugauchi, J. U.
2013-05-01
The Chicxulub impact structure, conclusively linked to the 65.5 Ma mass extinction, includes three sets of inward dipping, ring faults, between 70 and 130 km radially with a topographically elevated inner rim, at the inner edge of these faults except in the northeast where such a rim is absent. Slump blocks offset by large faults result in a terrace zone, that steps down from the inner rim into the annular trough. The inner blocks underlie the peak ring --an internal topographic ring of topography that exhibits variable relief due to target asymmetries and bounds the coherent melt sheet within the central basin. Impact breccias lie within the annular trough above the slump blocks and proximal ejecta and within the central basin above the melt sheet. Beneath the melt sheet is the top of the central uplift, displaced by >10 km vertically, and an upwarped Moho, displaced by 1-2 km. These interpretations and hydrocode models support the following working hypothesis for the formation of Chicxulub: a 50 km radius transient cavity, lined with melt and impact breccia, formed within 10s of seconds of the 65.5 Ma impact and within minutes, weakened rebounding crust rose above kilometers above the surface, the transient crater rim underwent localized, brittle deformation and collapsed into large slump blocks resulting in a inner rim being preserved 70-85 km from crater center, and ring faults forming farther outwards. The overheightened central uplift of weakened crust collapsed outwards forming the peak ring, and buried the inner slump blocks. Most impact melt that lined the transient cavity was transported on top of the central uplift, ultimately emplaced as a coherent <3-km thick melt sheet that shallows within the inner regions of the peak ring. Smaller pockets of melt flowed into the annular trough. During and likely for sometime after these events, slope collapse, proximal ejecta, ground surge, and tsunami waves infilled the annular trough with sediments up to 3 km thick and the central basin with sediments up to 900 m thick. Testing this working hypothesis requires direct observation and measurements on the impact materials, especially within and adjacent to the peak ring and central basin.
Colgan, Joseph P.; McPhee, Darcy K.; McDougall, Kristin; Hourigan, Jeremy K.
2013-01-01
We synthesized data from geologic maps, wells, seismic-reflection profiles, potential-field interpretations, and low-temperature thermochronology to refine our understanding of late Cenozoic extension and shortening in the Salinian block of the central California Coast Ranges. Data from the La Panza Range and southern Salinas Basin document early to middle Miocene extension, followed by Pliocene and younger shortening after a period of little deformation in the late Miocene. Extension took place on high-angle normal faults that accommodated ∼2% strain at the scale of the ∼50-km-wide Salinian block (oriented perpendicular to the San Andreas fault). Shortening was accommodated by new reverse faults, reactivation of older normal faults, and strike-slip faulting that resulted in a map-view change in the width of the Salinian block. The overall magnitude of shortening was ∼10% strain, roughly 4–5 times greater than the amount of extension. The timing and magnitude of deformation in our study area are comparable to that documented in other Salinian block basins, and we suggest that the entire block deformed in a similar manner over a similar time span. The timing and relative magnitude of extension and shortening may be understood in the context of central Coast Range tectonic boundary conditions linked to rotation of the western Transverse Ranges at the south end of the Salinian block. Older models for Coast Range shortening based on balanced fault-bend fold-style cross sections are a poor approximation of Salinian block deformation, and may lead to mechanically improbable fault geometries that overestimate the amount of shortening.
Millard, Daniel; Dang, Qianyu; Shi, Hong; Zhang, Xiaou; Strock, Chris; Kraushaar, Udo; Zeng, Haoyu; Levesque, Paul; Lu, Hua-Rong; Guillon, Jean-Michel; Wu, Joseph C; Li, Yingxin; Luerman, Greg; Anson, Blake; Guo, Liang; Clements, Mike; Abassi, Yama A; Ross, James; Pierson, Jennifer; Gintant, Gary
2018-04-27
Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, procedures, cell lines and reagents across laboratories makes comparisons of results difficult, leading to uncertainty about the role of hiPSC-CMs in defining proarrhythmic risk in drug discovery and regulatory submissions. A blinded pilot study was conducted to evaluate the electrophysiologic effects of eight well-characterized drugs on four cardiomyocyte lines using a standardized protocol across three microelectrode array (MEA) platforms (18 individual studies). Drugs were selected to define assay sensitivity of prominent repolarizing currents (E-4031 for IKr, JNJ303 for IKs) and depolarizing currents (nifedipine for ICaL, mexiletine for INa) as well as drugs affecting multi-channel block (flecainide, moxifloxacin, quinidine, and ranolazine). Inclusion criteria for final analysis was based on demonstrated sensitivity to IKr block (20% prolongation with E-4031) and L-type calcium current block (20% shortening with nifedipine). Despite differences in baseline characteristics across cardiomyocyte lines, multiple sites and instrument platforms, 10 of 18 studies demonstrated adequate sensitivity to IKr block with E-4031 and ICaL block with nifedipine for inclusion in the final analysis. Concentration-dependent effects on repolarization were observed with this qualified dataset consistent with known ionic mechanisms of single and multi-channel blocking drugs. hiPSC-CMs can detect repolarization effects elicited by single and multi-channel blocking drugs after defining pharmacologic sensitivity to IKr and ICaL block, supporting further validation efforts using hiPSC-CMs for cardiac safety studies.
Operating unit time use is associated with anaesthesia type in below-knee surgery in adults.
Lohela, T J; Chase, R P; Hiekkanen, T A; Kontinen, V K; Hynynen, M J
2017-03-01
Peripheral nerve blocks could reduce the operating unit and theatre time spent on high-risk patients who are particularly vulnerable to complications of general anaesthesia or have medications that prevent application of central neuraxial blocks. Medical record data of 617 and 254 elderly adults undergoing below-knee surgery in Jorvi and Meilahti hospitals (Helsinki University Hospital) between January 2010 and December 2012 were used to investigate the influence of anaesthetic technique on operating theatre times and on operating unit times using flexible parametric survival models. We report operating theatre and unit exit ratios (i.e. hazard ratios but using ratios of exit rates) for different types of anaesthesia. Adjusted analyses: In Jorvi Hospital, anaesthesia type was associated with large initial differentials in operating theatre times. The theatre exit ratios remained lower for general anaesthesia and central neuraxial blocks compared to peripheral nerve blocks until 30 min. In Meilahti Hospital, anaesthesia type did not influence theatre time, but was the best predictor of operating unit times. Compared to peripheral nerve blocks, the exit ratio remained lower for general anaesthesia until five operating unit hours in both hospitals and for central neuraxial blocks until 1 h in Meilahti Hospital and until 3 h in Jorvi Hospital. Holding area was used more in Jorvi Hospital compared to Meilahti Hospital. Peripheral nerve block anaesthesia reduces time spent in the operating unit and can reduce time spent in the operating theatre if induced in holding area outside of theatre. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Koyama, Takashi; Mirth, Christen K.
2016-01-01
In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size. PMID:26928023
Murat, Florent; Zhang, Rongzhi; Guizard, Sébastien; Flores, Raphael; Armero, Alix; Pont, Caroline; Steinbach, Delphine; Quesneville, Hadi; Cooke, Richard; Salse, Jerome
2013-01-01
Modern plant genomes are diploidized paleopolyploids. We revisited grass genome paleohistory in response to the diploidization process through a detailed investigation of the evolutionary fate of duplicated blocks. Ancestrally duplicated genes can be conserved, deleted, and shuffled, defining dominant (bias toward duplicate retention) and sensitive (bias toward duplicate erosion) chromosomal fragments. We propose a new grass genome paleohistory deriving from an ancestral karyotype structured in seven protochromosomes containing 16,464 protogenes and following evolutionary rules where 1) ancestral shared polyploidizations shaped conserved dominant (D) and sensitive (S) subgenomes, 2) subgenome dominance is revealed by both gene deletion and shuffling from the S blocks, 3) duplicate deletion/movement may have been mediated by single-/double-stranded illegitimate recombination mechanisms, 4) modern genomes arose through centromeric fusion of protochromosomes, leading to functional monocentric neochromosomes, 5) the fusion of two dominant blocks leads to supradominant neochromosomes (D + D = D) with higher ancestral gene retention compared with D + S = D (i.e., fusion of blocks with opposite sensitivity) or even S + S = S (i.e., fusion of two sensitive ancestral blocks). A new user-friendly online tool named “PlantSyntenyViewer,” available at http://urgi.versailles.inra.fr/synteny-cereal, presents the refined comparative genomics data. PMID:24317974
Receiver-exciter controller design
NASA Technical Reports Server (NTRS)
Jansma, P. A.
1982-01-01
A description of the general design of both the block 3 and block 4 receiver-exciter controllers for the Deep Space Network (DSN) Mark IV-A System is presented along with the design approach. The controllers are designed to enable the receiver-exciter subsystem (RCV) to be configured, calibrated, initialized and operated from a central location via high level instructions. The RECs are designed to be operated under the control of the DMC subsystem. The instructions are in the form of standard subsystem blocks (SSBs) received via the local area network (LAN). The centralized control provided by RECs and other DSCC controllers in Mark IV-A is intended to reduce DSN operations costs from the Mark III era.
Downtown Crossing: Auto Restricted Zone in Boston
DOT National Transportation Integrated Search
1982-07-01
The Downtown Crossing auto restricted zone, implemented in 1978, involved the : elimination of all auto traffic froma zone of twelve blocks encompassing six : different streets in Bostn's central business district. Some of the blocks were : pedestria...
He, Fang; Kiener, Tanja K; Lim, Xiao Fang; Tan, Yunrui; Raj, Kattur Venkatachalam Ashok; Tang, Manli; Chow, Vincent T K; Chen, Qingfeng; Kwang, Jimmy
2013-01-01
Human Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease (HFMD) in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no efficient universal antibody test available to detect EV71 infections. In the present study, an epitope-blocking ELISA was developed to detect specific antibodies to human EV71 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (Mab 1C6) that specifically binds to capsid proteins in whole EV71 viruses without any cross reaction to any EV71 capsid protein expressed alone. The sensitivity and specificity of the epitope-blocking ELISA for EV71 was evaluated and compared to microneutralization using immunized animal sera to multiple virus genotypes of EV71 and coxsackieviruses. Further, 200 serum sample from human individuals who were potentially infected with EV71 viruses were tested in both the blocking ELISA and microneutralization. Results indicated that antibodies to EV71 were readily detected in immunized animals or human sera by the epitope blocking ELISA whereas specimens with antibodies to other enteroviruses yielded negative results. This assay is not only simpler to perform but also shows higher sensitivity and specificity as compared to microneutralization. The epitope-blocking ELISA based on a unique Mab 1C6 provided highly sensitive and 100% specific detection of antibodies to human EV71 viruses in human sera.
A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium
Araneda, Ricardo C; Peterlin, Zita; Zhang, Xinmin; Chesler, Alex; Firestein, Stuart
2004-01-01
Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca2+ imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30μm). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing. PMID:14724183
Identifying block structure in the Pacific Northwest, USA
Savage, James C.; Wells, Ray E.
2015-01-01
We have identified block structure in the Pacific Northwest (west of 116°W between 38°N and 49°N) by clustering GPS stations so that the same Euler vector approximates the velocity of each station in a cluster. Given the total number k of clusters desired, the clustering procedure finds the best assignment of stations to clusters. Clustering is calculated for k= 2 to 14. In geographic space, cluster boundaries that remain relatively stable as k is increased are tentatively identified as block boundaries. That identification is reinforced if the cluster boundary coincides with a geologic feature. Boundaries identified in northern California and Nevada are the Central Nevada Seismic Belt, the west side of the Northern Walker Lane Belt, and the Bartlett Springs Fault. Three blocks cover all of Oregon and Washington. The principal block boundary there extends west-northwest along the Brothers Fault Zone, then north and northwest along the eastern boundary of Siletzia, the accreted oceanic basement of the forearc. East of this boundary is the Intermountain block, its eastern boundary undefined. A cluster boundary at Cape Blanco subdivides the forearc along the faulted southern margin of Siletzia. South of Cape Blanco the Klamath Mountains-Basin and Range block extends east to the Central Nevada Seismic Belt and south to the Sierra Nevada-Great Valley block. The Siletzia block north of Cape Blanco coincides almost exactly with the accreted Siletz terrane. The cluster boundary in the eastern Olympic Peninsula may mark permanent shortening of Siletzia against the Intermountain block.
Nijs, Jo; Van Houdenhove, Boudewijn; Oostendorp, Rob A B
2010-04-01
Central sensitization plays an important role in the pathophysiology of numerous musculoskeletal pain disorders, yet it remains unclear how manual therapists can recognize this condition. Therefore, mechanism based clinical guidelines for the recognition of central sensitization in patients with musculoskeletal pain are provided. By using our current understanding of central sensitization during the clinical assessment of patients with musculoskeletal pain, manual therapists can apply the science of nociceptive and pain processing neurophysiology to the practice of manual therapy. The diagnosis/assessment of central sensitization in individual patients with musculoskeletal pain is not straightforward, however manual therapists can use information obtained from the medical diagnosis, combined with the medical history of the patient, as well as the clinical examination and the analysis of the treatment response in order to recognize central sensitization. The clinical examination used to recognize central sensitization entails the distinction between primary and secondary hyperalgesia. Copyright 2009 Elsevier Ltd. All rights reserved.
Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara
2015-01-01
Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with NSAIDs. The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain while a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present studies, palpation of the ipsilateral hindlimb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced FOS expression in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways by microinjection of lidocaine within the rostral ventromedial medulla (RVM) induced conditioned place preference (CPP) selectively in rats treated with the high dose of MIA. CPP to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, i.p. at −30 min). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that may guide drug discovery for treatment of advanced OA pain without the need for joint replacement. PMID:26694132
Huchet, A M; Schmitt, H
1986-01-01
The cardiovascular effects of nicergoline, a preferential alpha 1-adrenoceptor blocking drug, were studied in anaesthetized normotensive or spontaneously hypertensive (SH) rats. Nicergoline (300 micrograms/kg, i.v.) significantly reduced blood pressure and heart rate in control, bivagotomized or beta-blocked normotensive or SH rats. In bilaterally vagotomized and beta-blocked rats, nicergoline reduced mean blood pressure but did no longer modify heart rate. Thus, it is postulated that nicergoline could reduce the sympathetic tone and increase the vagal nerve activity, possibly by inhibiting central alpha 1-adrenoceptors. The nicergoline--induced bradycardia was greater in bivagotomized SHR than in normotensive ones. Intracerebroventricular injections of nicergoline (30 micrograms/kg) did not modify heart rate in normotensive control, bivagotomized or beta-blocked rats. On the contrary, nicergoline (30 micrograms/kg) injected into the cisterna magna induced a significant bradycardia in the three groups of normotensive rats. Blood pressure was reduced in the same way in all groups centrally treated by nicergoline. In conclusion, it seems that nicergoline reduces blood pressure by peripheral alpha-adrenoceptor blockade and modulates the autonomic nervous activity by inhibiting alpha 1-adrenoceptors mainly localized in the brainstem.
The Effect of Ocular Surface Regularity on Contrast Sensitivity and Straylight in Dry Eye.
Koh, Shizuka; Maeda, Naoyuki; Ikeda, Chikako; Asonuma, Sanae; Ogawa, Mai; Hiraoka, Takahiro; Oshika, Tetsuro; Nishida, Kohji
2017-05-01
To investigate the association between visual function and ocular surface regularity in dry eye. We enrolled 52 eyes of 52 dry eye patients (34 dry eyes with superficial punctate keratopathy [SPK] in the central corneal region [central SPK] and 18 dry eyes without central SPK) and 20 eyes of 20 normal control subjects. All eyes had a best-corrected distance visual acuity better than 20/20. We measured two indices of contrast sensitivity function under photopic conditions: contrast sensitivity and letter contrast sensitivity. The area under the log contrast sensitivity function (AULCSF) was calculated from the obtained contrast sensitivity data. Straylight was quantified using a straylight meter. Dry eyes with central SPK had significantly decreased contrast sensitivity function, including AULCSF and letter contrast sensitivity than those without central SPK and normal eyes (P < 0.05 for each). While the straylight values in both dry eye groups did not differ, straylight values were greater than those in normal eyes (P < 0.05 for both). In dry eye, the AULCSF and letter contrast sensitivity negatively correlated with the central SPK score (R = -0.485, P < 0.001, and R = -0.541, P < 0.001, respectively). In dry eye, reduced contrast sensitivity in part results from central SPK overlying the optical zone and the increased straylight results from tear film instability rather than central SPK.
Lin, Chia-Hsien; Tsai, Ming-Cheng
2005-05-01
The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials were studied on the RP1 central neuron of giant African snails (Achatina fulica Ferussac). Extra-cellular application of d-amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin, propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d-amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP. U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP, whereas they did not block the d-amphetamine-elicited BoP in the same neuron. These results suggest that BoP elicited by d-amphetamine or procaine were associated with protein kinase A and phospholipase C activity in the neuron.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Margulis, Katherine; Zhang, Xiangyi; Joubert, Lydia -Marie
Template–free fabrication of non–spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self–assembly from aqueous solutions at room temperature. Nanocubes with edges of 40–200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks. These polymers self–assemble into 28±5 nm micelles in water. Upon drying, micelle aggregation and a kinetically controlled crystallization of central blocks evidently induce solidmore » cubic particle formation. An approach for preserving the structures of these cubes in water by thiol– or photo–induced crosslinking was developed. In conclusion, the ability to solubilize a model hydrophobic drug, curcumin, was also explored.« less
Margulis, Katherine; Zhang, Xiangyi; Joubert, Lydia -Marie; ...
2017-10-27
Template–free fabrication of non–spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self–assembly from aqueous solutions at room temperature. Nanocubes with edges of 40–200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks. These polymers self–assemble into 28±5 nm micelles in water. Upon drying, micelle aggregation and a kinetically controlled crystallization of central blocks evidently induce solidmore » cubic particle formation. An approach for preserving the structures of these cubes in water by thiol– or photo–induced crosslinking was developed. In conclusion, the ability to solubilize a model hydrophobic drug, curcumin, was also explored.« less
Robert E. Bardon; David W. Countryman
1993-01-01
This paper reports the first year survival and growth of red oak seedlings underplanted in two mixed upland hardwood stands in south central Iowa. The underplanted seedlings were undercut and not undercut 1-0 red oak stock. Fifteen blocks were laid out in 1990, with seven of the blocks receiving a foliar application of glyphosate herbicide. In the winter of 1990-1991,...
Fernández-Soto, Pedro; Mvoulouga, Prosper Obolo; Akue, Jean Paul; Abán, Julio López; Santiago, Belén Vicente; Sánchez, Miguel Cordero; Muro, Antonio
2014-01-01
The filarial parasite Loa loa, the causative agent of loiasis, is endemic in Central and Western Africa infecting 3-13 million people. L. loa has been associated with fatal encephalopathic reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic method routinely used is the microscopic examination of mid-day blood samples by thick blood film. Improved methods for detection of L. loa are needed in endemic regions with limited resources, where delayed diagnosis results in high mortality. We have investigated the use of a loop-mediated isothermal amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm was used to optimize the LAMP conditions using a thermocycler or a conventional heating block. Amplification of DNA in the LAMP mixture was visually inspected for turbidity as well as addition of fluorescent dye. LAMP specificity was evaluated using DNA from other parasites; sensitivity was evaluated using DNA from L. loa 10-fold serially diluted. Simulated human blood samples spiked with DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent dye, all positive reactions turned green while the negative controls remained orange under ambient light. After electrophoresis on agarose gels, a ladder of multiple bands of different sizes could be observed in positive samples. The detection limit of the assay was found to be as little as 0.5 ag of L. loa genomic DNA when using a heating block. We have designed, for the first time, a highly sensitive LAMP assay for the detection of L. loa which is potentially adaptable for field diagnosis and disease surveillance in loiasis-endemic areas.
Fernández-Soto, Pedro; Mvoulouga, Prosper Obolo; Akue, Jean Paul; Abán, Julio López; Santiago, Belén Vicente; Sánchez, Miguel Cordero; Muro, Antonio
2014-01-01
The filarial parasite Loa loa, the causative agent of loiasis, is endemic in Central and Western Africa infecting 3–13 million people. L. loa has been associated with fatal encephalopathic reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic method routinely used is the microscopic examination of mid-day blood samples by thick blood film. Improved methods for detection of L. loa are needed in endemic regions with limited resources, where delayed diagnosis results in high mortality. We have investigated the use of a loop-mediated isothermal amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm was used to optimize the LAMP conditions using a thermocycler or a conventional heating block. Amplification of DNA in the LAMP mixture was visually inspected for turbidity as well as addition of fluorescent dye. LAMP specificity was evaluated using DNA from other parasites; sensitivity was evaluated using DNA from L. loa 10-fold serially diluted. Simulated human blood samples spiked with DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent dye, all positive reactions turned green while the negative controls remained orange under ambient light. After electrophoresis on agarose gels, a ladder of multiple bands of different sizes could be observed in positive samples. The detection limit of the assay was found to be as little as 0.5 ag of L. loa genomic DNA when using a heating block. We have designed, for the first time, a highly sensitive LAMP assay for the detection of L. loa which is potentially adaptable for field diagnosis and disease surveillance in loiasis-endemic areas. PMID:24722638
Leffler, Andreas; Linte, Ramona Madalina; Nau, Carla; Reeh, Peter; Babes, Alexandru
2007-07-01
Heat-activated ion channels from the vanilloid-type TRP group (TRPV1-4) seem to be central for heat-sensitivity of nociceptive sensory neurons. Displaying a high-threshold (> 52 degrees C) for activation, TRPV2 was proposed to act as a sensor for intense noxious heat in mammalian sensory neurons. However, although TRPV2 is expressed in a distinct population of thinly myelinated primary afferents, a widespread expression in a variety of neuronal and non-neuronal tissues suggests a more diverse physiological role of TRPV2. In its role as a heat-sensor, TRPV2 has not been thoroughly characterized in terms of biophysical and pharmacological properties. In the present study, we demonstrate that the features of heterologously expressed rat TRPV2 closely resemble those of high-threshold heat-evoked currents in medium- and large-sized capsaicin-insensitive rat dorsal root ganglion (DRG) neurons. Both in TRPV2-expressing human embryonic kidney (HEK)293t cells and in DRGs, high-threshold heat-currents were sensitized by repeated activation and by the TRPV1-3 agonist, 2-aminoethoxydiphenyl borate (2-APB). In addition to a previously described block by ruthenium red, we identified the trivalent cations, lanthanum (La(3+)) and gadolinium (Gd(3+)) as potent blockers of TRPV2. Thus, we present a new pharmacological tool to distinguish between heat responses of TRPV2 and the closely related capsaicin-receptor, TRPV1, which is strongly sensitized by trivalent cations. We demonstrate that self-sensitization of heat-evoked currents through TRPV2 does not require extracellular calcium and that TRPV2 can be activated in cell-free membrane patches in the outside-out configuration. Taken together our results provide new evidence for a role of TRPV2 in mediating high-threshold heat responses in a subpopulation of mammalian sensory neurons.
NASA Astrophysics Data System (ADS)
Gourley, J. R.; Byrne, T.
2005-12-01
An integrated data set of earthquake locations (Taiwan's Central Weather Bureau), focal mechanisms from the Broadband Array of Taiwan Seismicity (BATS), GPS velocities and geologic data are combined to constrain the geometry and kinematics of a crustal block within the metamorphic basement of Taiwan's northeastern Central Range. The active block is bounded by two parallel seismic zones that accommodate uplift and northeastward oblique lateral extrusion. The western shear zone is a region that dips vertically to steeply west and projects generally to the western boundary between the Slate Belt and pre-Tertiary metamorphic basement. BATS focal mechanisms consistently show east-side-up, left-lateral normal displacements. Late-stage geologic structures published previously show left-lateral faulting followed by east-west extension. The eastern shear zone dips vertically to steeply west and projects to the eastern boundary of the metamorphic basement, which correlates with the eastern mountain front in this area. BATS focal mechanisms show west-side-up reverse displacements. The kinematics of these two zones define a crustal scale block that is interpreted to be moving up and northeast towards the Okinawa Trough. The extrusion of this crustal block may be driven in part by the topographic difference between the Central Range and the Okinawa Trough, as well as by the active collision between the Philippine Sea Plate and the Eurasian basement high. This proposed northeastern lateral extrusion mirrors the active lateral extrusion in southwestern Taiwan which is observed on the southern side of the Eurasian basement high collision. The involvement of the basement high in the collision and adjacent regions appears to be an important factor in understanding local structural variations in the arc-continent collision and should be considered in both forward and reverse modeling of Taiwan deformation.
Performance evaluation for 120 four-layer DOI block detectors of the jPET-D4.
Inadama, Naoko; Murayama, Hideo; Ono, Yusuke; Tsuda, Tomoaki; Hamamoto, Manabu; Yamaya, Taiga; Yoshida, Eiji; Shibuya, Kengo; Nishikido, Fumihiko; Takahashi, Kei; Kawai, Hideyuki
2008-01-01
The jPET-D4 is a brain positron emission tomography (PET) scanner that we have developed to meet user demands for high sensitivity and high spatial resolution. For this scanner, we developed a four-layer depth-of-interaction (DOI) detector. The four-layer DOI detector is a key component for the jPET-D4, its performance has great influence on the overall system performance. Previously, we reported the original technique for encoding four-layer DOI. Here, we introduce the final design of the jPET-D4 detector and present the results of an investigation on uniformity in performance of the detector. The performance evaluation was done over the 120 DOI crystal blocks for the detectors, which are to be assembled into the jPET-D4 scanner. We also introduce the crystal assembly method, which is simple enough, even though each DOI crystal block is composed of 1,024 crystal elements. The jPET-D4 detector consists of four layers of 16 x 16 Gd(2)SiO(5) (GSO) crystals and a 256-channel flat-panel position-sensitive photomultiplier tube (256ch FP-PMT). To identify scintillated crystals in the four-layer DOI detector, we use pulse shape discrimination and position discrimination on the two-dimensional (2D) position histogram. For pulse shape discrimination, two kinds of GSO crystals that show different scintillation decay time constants are used in the upper two and lower two layers, respectively. Proper reflector arrangement in the crystal block then allows the scintillated crystals to be identified in these two-layer groupings with two 2D position histograms. We produced the 120 DOI crystal blocks for the jPET-D4 system, and measured their characteristics such as the accuracy of pulse shape discrimination, energy resolution, and the pulse height of the full energy peak. The results show a satisfactory and uniform performance of the four-layer DOI crystal blocks; for example, misidentification rate in each GSO layer is <5% based on pulse shape discrimination, the averaged energy resolutions for the central four crystals of the first (farthest from the FP-PMT), second, third, and 4th layers are 15.7 +/- 1.0, 15.8 +/- 0.6, 17.7 +/- 1.2, and 17.3 +/- 1.4%, respectively, and variation in pulse height of the full energy peak among the four layers is <5% on average.
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 Liposomal Bupivacaine did not develop mechanical allodynia following exposure to stress, but did develop social avoidance behavior. Neither drug affected stress-induced activation of monocytes in the bone marrow, blood, or brain. Neuroinflammatory responses developed in all treatment groups, as evidenced by elevated IL-1β mRNA levels in the brain and spinal cord after RSD. In this study, psychosocial stress was associated with increased pain sensitivity in mice. Development of mechanical allodynia with RSD was blocked by regional analgesia with local anesthetics, Ropivacaine or Liposomal Bupivacaine. Despite blocking mechanical allodynia, these anesthetic interventions did not prevent neuroimmune activation or social avoidance associated with RSD. These data suggest that stress-induced neuroinflammatory changes are not associated with increased sensitivity to pain following RSD. Thus, blocking peripheral nociception was effective in inhibiting enhanced pain signaling without altering stress-induced immune or behavioral responses. Copyright © 2017 Elsevier Inc. All rights reserved.
Light-enabled reversible self-assembly and tunable optical properties of stable hairy nanoparticles
NASA Astrophysics Data System (ADS)
Chen, Yihuang; Wang, Zewei; He, Yanjie; Yoon, Young Jun; Jung, Jaehan; Zhang, Guangzhao; Lin, Zhiqun
2018-02-01
The ability to dynamically organize functional nanoparticles (NPs) via the use of environmental triggers (temperature, pH, light, or solvent polarity) opens up important perspectives for rapid and convenient construction of a rich variety of complex assemblies and materials with new structures and functionalities. Here, we report an unconventional strategy for crafting stable hairy NPs with light-enabled reversible and reliable self-assembly and tunable optical properties. Central to our strategy is to judiciously design amphiphilic star-like diblock copolymers comprising inner hydrophilic blocks and outer hydrophobic photoresponsive blocks as nanoreactors to direct the synthesis of monodisperse plasmonic NPs intimately and permanently capped with photoresponsive polymers. The size and shape of hairy NPs can be precisely tailored by modulating the length of inner hydrophilic block of star-like diblock copolymers. The perpetual anchoring of photoresponsive polymers on the NP surface renders the attractive feature of self-assembly and disassembly of NPs on demand using light of different wavelengths, as revealed by tunable surface plasmon resonance absorption of NPs and the reversible transformation of NPs between their dispersed and aggregated states. The dye encapsulation/release studies manifested that such photoresponsive NPs may be exploited as smart guest molecule nanocarriers. By extension, the star-like block copolymer strategy enables the crafting of a family of stable stimuli-responsive NPs (e.g., temperature- or pH-sensitive polymer-capped magnetic, ferroelectric, upconversion, or semiconducting NPs) and their assemblies for fundamental research in self-assembly and crystallization kinetics of NPs as well as potential applications in optics, optoelectronics, magnetic technologies, sensory materials and devices, catalysis, nanotechnology, and biotechnology.
Ye, Rui; Liu, Jun; Jia, Zhiying; Wang, Hongyang; Wang, YongAn; Sun, Wei; Wu, Xuan; Zhao, Zhifei; Niu, Baolong; Li, Xingqi; Dai, Guanghai; Li, Jianxiong
2016-06-13
BACKGROUND There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. MATERIAL AND METHODS Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen's cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. RESULTS ATP (0.1-10 µM) reduced the potassium current (IK+) in the majority of the recorded Hensen's cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 µM to 10 mM), which was reversibly blocked by 100 µM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. CONCLUSIONS Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL).
Bradykinin Induces TRPV1 Exocytotic Recruitment in Peptidergic Nociceptors
Mathivanan, Sakthikumar; Devesa, Isabel; Changeux, Jean-Pierre; Ferrer-Montiel, Antonio
2016-01-01
Transient receptor potential vanilloid I (TRPV1) sensitization in peripheral nociceptors is a prominent phenomenon that occurs in inflammatory pain conditions. Pro-algesic agents can potentiate TRPV1 activity in nociceptors through both stimulation of its channel gating and mobilization of channels to the neuronal surface in a context dependent manner. A recent study reported that ATP-induced TRPV1 sensitization in peptidergic nociceptors involves the exocytotic release of channels trafficked by large dense core vesicles (LDCVs) that cargo alpha-calcitonin gene related peptide alpha (αCGRP). We hypothesized that, similar to ATP, bradykinin may also use different mechanisms to sensitize TRPV1 channels in peptidergic and non-peptidergic nociceptors. We found that bradykinin notably enhances the excitability of peptidergic nociceptors, and sensitizes TRPV1, primarily through the bradykinin receptor 2 pathway. Notably, bradykinin sensitization of TRPV1 in peptidergic nociceptors was significantly blocked by inhibiting Ca2+-dependent neuronal exocytosis. In addition, silencing αCGRP gene expression, but not substance P, drastically reduced bradykinin-induced TRPV1 sensitization in peptidergic nociceptors. Taken together, these findings indicate that bradykinin-induced sensitization of TRPV1 in peptidergic nociceptors is partially mediated by the exocytotic mobilization of new channels trafficked by αCGRP-loaded LDCVs to the neuronal membrane. Our findings further imply a central role of αCGRP peptidergic nociceptors in peripheral algesic sensitization, and substantiate that inhibition of LDCVs exocytosis is a valuable therapeutic strategy to treat pain, as it concurrently reduces the release of pro-inflammatory peptides and the membrane recruitment of thermoTRP channels. PMID:27445816
Income convergence in a rural, majority African American region
Buddhi Gyawali; Rory Fraser; James Bukenya; John Schelhas
2008-01-01
This paper revisits the issue of income convergence by examining the question of whether poorer Census Block Groups have been catching up with wealthier Census Block Groups over the 1980-2000 period. The dataset consists of 161 Census Block Groups in Alabamaâs west-central Black Belt region. Estimates of a spatial lag model provide support for the conditional...
Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica
2011-05-01
Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd
A novel hypothesis about mechanisms affecting conduction velocity of central myelinated fibers.
Adriano, Enrico; Perasso, Luisa; Panfoli, Isabella; Ravera, Silvia; Gandolfo, Carlo; Mancardi, Gianluigi; Morelli, Alessandro; Balestrino, Maurizio
2011-10-01
The hypothesis that gap junctions are implicated in facilitating axonal conduction has not yet been experimentally demonstrated at the electrophysiological level. We found that block of gap junctions with oleammide slows down axonal conduction velocity in the hippocampal Schaffer collaterals, a central myelinated pathway. Moreover, we explored the possibility that support by the oligodendrocyte to the axon involves energy metabolism, a hypothesis that has been recently proposed by some of us. In agreement with this hypothesis, we found that the effect of oleammide was reversed by pretreatment with creatine, a compound that is known to increase the energy charge of the tissue. Moreover, conduction velocity was also slowed down by anoxia, a treatment that obviously decreases the energy charge of the tissue, and by ouabain, a compound that blocks plasma membrane Na/K-ATPase, the main user of ATP in the brain. We hypothesize that block of gap junctions slows down conduction velocity in central myelinated pathways because oligodendrocytes synthesize ATP and transfer it to the axon through gap junctions.
Kaneko, T; Thompson, R F
1997-05-01
Central muscarinic cholinergic involvement in classical conditioning of eyeblink responses was determined in trace and delay paradigms. Rabbits were trained on a trace procedure in which a 250-ms tone conditioned stimulus (CS) and a 100-ms air-puff unconditioned stimulus (UCS) were presented with a 500-ms trace interval. Each training session day consisted of ten tone alone, ten air-puff alone and 80 paired CS-UCS trials. Scopolamine hydrochloride at doses of 0.03 and 0.1 mg/0.5 ml per kg, s.c. dose-dependently disrupted acquisition of conditioned responses. Rabbits that were treated with scopolamine and failed to learn showed a gradual increase in conditioned responses during an additional training period with saline injections and no transfer from earlier training. Scopolamine methyl bromide, which does not appreciably cross the blood-brain barrier, showed no effects in the trace conditioning paradigm at a dose of 0.1 mg/kg, s.c., indicating central cholinergic blockade is responsible for the suppressive effect of scopolamine. Scopolamine hydrochloride at a dose of 0.1 mg/kg, s.c. did not block acquisition in the delay procedure with a 250-ms inter-stimulus interval, although the rate of acquisition was somewhat reduced by the drug. These data are the first to demonstrate that classical conditioning of the eyeblink response in the trace procedure is highly sensitive to central cholinergic deficits.
Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L; Morgan, Donald A; Pitz, Kate M; Rice, Olivia M; Roghair, Robert D
2016-08-01
Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.
The influence of ozone forcing on blocking in the Southern Hemisphere
NASA Astrophysics Data System (ADS)
Dennison, Fraser W.; McDonald, Adrian; Morgenstern, Olaf
2016-12-01
We investigate the influence of ozone depletion and recovery on tropospheric blocking in the Southern Hemisphere. Blocking events are identified using a persistent positive anomaly method applied to 500 hPa geopotential height. Using the National Institute for Water and Atmospheric Research-United Kingdom Chemistry and Aerosols chemistry-climate model, we compare reference runs that include forcing due to greenhouse gases (GHGs) and ozone-depleting substances to sensitivity simulations in which ozone-depleting substances are fixed at their 1960 abundances and other sensitivity simulations with GHGs fixed at their 1960 abundances. Blocking events in the South Atlantic are shown to follow stratospheric positive anomalies in the Southern Annular Mode (SAM) index; this is not the case for South Pacific blocking events. This relationship means that summer ozone depletion, and corresponding positive SAM anomalies, leads to an increased frequency of blocking in the South Atlantic while having little effect in the South Pacific. Similarly, ozone recovery, having the opposite effect on the SAM, leads to a decline in blocking frequency in the South Atlantic, although this may be somewhat counteracted by the effect of increasing GHGs.
Peripheral input and its importance for central sensitization.
Baron, Ralf; Hans, Guy; Dickenson, Anthony H
2013-11-01
Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.
"Eyeball test" of thermographic patterns for predicting a successful lateral infraclavicular block.
Andreasen, Asger M; Linnet, Karen E; Asghar, Semera; Rothe, Christian; Rosenstock, Charlotte V; Lange, Kai H W; Lundstrøm, Lars H
2017-11-01
Increased distal skin temperature can be used to predict the success of lateral infraclavicular (LIC) block. We hypothesized that an "eyeball test" of specific infrared thermographic patterns after LIC block could be used to determine block success. In this observational study, five observers trained in four distinct thermographic patterns independently evaluated thermographic images of the hands of 40 patients at baseline and at one-minute intervals for 30 min after a LIC block. Sensitivity, specificity, and predictive values of a positive and a negative test were estimated to evaluate the validity of specific thermographic patterns for predicting a successful block. Sensory and motor block of the musculocutaneous, radial, ulnar, and median nerves defined block success. Fleiss' kappa statistics of multiple interobserver agreements were used to evaluate reliability. As a diagnostic test, the defined specific thermographic patterns of the hand predicted a successful block with increasing accuracy over the 30-min observation period. Block success was predicted with a sensitivity of 92.4% (95% confidence interval [CI], 86.8 to 96.2) and with a specificity of 84.0% (95% CI, 70.3 to 92.4) at min 30. The Fleiss' kappa for the five observers was 0.87 (95% CI, 0.77 to 0.96). We conclude that visual evaluation by an eyeball test of specific thermographic patterns of the blocked hands may be useful as a valid and reliable diagnostic test for predicting a successful LIC block.
NASA Astrophysics Data System (ADS)
Alonso-Henar, Jorge; Alvarez-Gomez, José Antonio; Jesús Martinez-Diaz, José
2017-04-01
The Central American Volcanic Arc (CAVA) is located at the western margin of the Caribbean plate, over the Chortís Block, spanning from Guatemala to Costa Rica. The CAVA is associated to the subduction of the Cocos plate under the Caribbean plate at the Middle America Trench. Our study is focused in the Salvadorian CAVA segment, which is tectonically characterized by the presence of the El Salvador Fault Zone (ESFZ), part of the western boundary of a major block forming the Caribbean plate (the Chortis Block). The structural evolution of the western boundary of the Chortis Block, particularly in the CAVA crossing El Salvador remains unknown. We have done a kinematic analysis from seismic and fault slip data and combined our results with a review of regional previous studies. This approach allowed us to constrain the tectonic evolution and the forces that control the deformation in northern Central America. Along the active volcanic arc we identified active transtensional deformation. On the other hand, we have identified two deformation phases in the back arc region: A first one of transpressional wrenching close to simple shearing (Miocene); and a second one characterized by almost E-W extension. Our results reveal a change from transpressional to transtensional shearing coeval with a migration of the volcanism towards the trench in Late Miocene times. This strain change could be related with a coupled to decoupled transition on the Cocos - Caribbean subduction interface, which could be related to a slab roll-back of the Cocos Plate beneath the Chortis Block. The combination of different degrees of coupling on the subduction interface, together with a constant relative eastward drift of the Caribbean Plate, control the deformation style along the western boundary of the Chortis Block.
A geological interpretation of Seasat-SAR imagery of Jamaica
NASA Technical Reports Server (NTRS)
Wadge, G.; Dixon, T. H.
1984-01-01
Spaceborne radar imagery obtained from Seasat allows an unobscured large-scale view of Jamaica that can be used for geological interpretation. Lineaments and textures visible in these images were mapped and compared with the known geology of the Tertiary karst limestones covering the central and western parts of the island. Some of these radar textures correlate with lithological units, while others follow tectonically-controlled zones or structural blocks. Mapping of radar lineaments has led to the recognition of three new aspects of Jamaican faults: (1) a major through-going NE-SW fault system, termed here the Vere-Annotto lineament; (2) a series of curving scissor faults in the central part of the island; and (3) the related observation that the dominant NNW-SSE tectonic fabric of the central part of the island takes the form of an elongate sigmoid in plan view. During most of the Neogene Jamaica has been part of an active zone of left-lateral transform motion between the Caribbean and North American plates and is a region of anomalous uplift. The radar imagery is a sensitive recorder of the deformation undergone by the karst limestones in this tectonic regime. Some of the observations are explained with models for a complex, evolving shear zone.
Central sensitization: Implications for the diagnosis and treatment of pain
Woolf, Clifford J
2010-01-01
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and postsurgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk both of developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. PMID:20961685
Block structure and geodynamics of the continental lithosphere on plate boundaries
NASA Astrophysics Data System (ADS)
Gatinsky, Yu. G.; Prokhorova, T. V.; Romanyuk, T. V.; Vladova, G. L.
2009-04-01
Division of the Earth lithosphere on large plates must be considered only as the first and most general approximation in its structure hierarchy. Some transit zones or difuuse boundaries after other authors take place in lithosphere plate boundaries. The tectonic tension of plate interaction is transferred and relaxed within these zones, which consist of blocks limited by seismoactive faults. Vectors of block horizontal displacements often don't coincide with vectors of main plates and change together with changing block rigidity. As a rule the intensity the seismic energy at plate and transit zone boundaries decreases linearly with distancing from these boundaries and correlates with decreasing of velocities of block horizontal displacements. But sometimes the maximum of the energy manifestation takes place in inner parts of transit zones. Some relatively tight interblock zones established in central and east Asia are the most seismically active. They limited such blocks as Pamir, Tien Shan, Bayanhar, Shan, Japanese-Korean, as well as the north boundary of the Indian Plate. A seismic energy intensity of these zones can be compared with the energy of Pacific subduction zones. It is worthy to note that the majority catastrophic earthquakes took place in Central Asia just within interblock zones. A level of block displacement is situated mainly in the bottom or inside the Earth crust, more rare in the lithosphere mantle. Blocks with the most thick lithosphere roots (SE China, Amurian) are the most rigid and weakly deformed.
Abushik, Polina A; Niittykoski, Minna; Giniatullina, Raisa; Shakirzyanova, Anastasia; Bart, Genevieve; Fayuk, Dmitriy; Sibarov, Dmitry A; Antonov, Sergei M; Giniatullin, Rashid
2014-04-01
Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore the mechanism of HCY action, we studied short- and long-term effects of this amino acid on rat peripheral and central neurons. HCY induced intracellular Ca²⁺ transients in cultured trigeminal neurons and satellite glial cells (SGC), which were blocked by the NMDA antagonist AP-5 in neurons, but not in SGCs. In contrast, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP), the metabotropic mGluR5 (metabotropic glutamate receptor 5 subtype) antagonist, preferentially inhibited Ca²⁺ transients in SGCs. Prolonged application of HCY induced apoptotic cell death of both kinds of trigeminal cells. The apoptosis was blocked by AP-5 or by the mGluR5 antagonist MTEP. Likewise, in cortical neurons, HCY-induced cell death was inhibited by AP-5 or MTEP. Imaging with 2',7'-dichlorodihydrofluorescein diacetate or mitochondrial dye Rhodamine-123 as well as thiobarbituric acid reactive substances assay did not reveal involvement of oxidative stress in the action of HCY. Thus, elevation of intracellular Ca²⁺ by HCY in neurons is mediated by NMDA and mGluR5 receptors while SGC are activated through the mGluR5 subtype. Long-term neurotoxic effects in peripheral and central neurons involved both receptor types. Our data suggest glutamatergic mechanisms of HCY-induced sensitization and apoptosis of trigeminal nociceptors. © 2013 International Society for Neurochemistry.
On the late-time behavior of Virasoro blocks and a classification of semiclassical saddles
Fitzpatrick, A. Liam; Kaplan, Jared
2017-04-12
Recent work has demonstrated that black hole thermodynamics and information loss/restoration in AdS 3/CFT 2 can be derived almost entirely from the behavior of the Virasoro conformal blocks at large central charge, with relatively little dependence on the precise details of the CFT spectrum or OPE coefficients. Here, we elaborate on the non-perturbative behavior of Virasoro blocks by classifying all ‘saddles’ that can contribute for arbitrary values of external and internal operator dimensions in the semiclassical large central charge limit. The leading saddles, which determine the naive semiclassical behavior of the Virasoro blocks, all decay exponentially at late times, andmore » at a rate that is independent of internal operator dimensions. Consequently, the semiclassical contribution of a finite number of high-energy states cannot resolve a well-known version of the information loss problem in AdS 3. Furthermore, we identify two infinite classes of sub-leading saddles, and one of these classes does not decay at late times.« less
On the late-time behavior of Virasoro blocks and a classification of semiclassical saddles
NASA Astrophysics Data System (ADS)
Fitzpatrick, A. Liam; Kaplan, Jared
2017-04-01
Recent work has demonstrated that black hole thermodynamics and information loss/restoration in AdS3/CFT2 can be derived almost entirely from the behavior of the Virasoro conformal blocks at large central charge, with relatively little dependence on the precise details of the CFT spectrum or OPE coefficients. Here, we elaborate on the non-perturbative behavior of Virasoro blocks by classifying all `saddles' that can contribute for arbitrary values of external and internal operator dimensions in the semiclassical large central charge limit. The leading saddles, which determine the naive semiclassical behavior of the Virasoro blocks, all decay exponentially at late times, and at a rate that is independent of internal operator dimensions. Consequently, the semiclassical contribution of a finite number of high-energy states cannot resolve a well-known version of the information loss problem in AdS3. However, we identify two infinite classes of sub-leading saddles, and one of these classes does not decay at late times.
24. Perspective view of central tower from roof of main ...
24. Perspective view of central tower from roof of main block, looking northeast, with HABS team - National Home for Disabled Volunteer Soldiers, Northwestern Branch, Main Building, 5000 West National Avenue, Milwaukee, Milwaukee County, WI
Rosenthal, Erika
2005-01-01
The agrochemical industry is using trade agreements to block proposed bans on pesticides identified as the worst occupational health hazards by a multi-country illness surveillance program in Central America. Through privileged access to closed-door negotiations, industry inserted deregulatory mechanisms, including a regional pesticide registry that invalidates national laws, investors' rights protection, and increased intellectual property protections, into the draft Central American Customs Union and the Central American Free Trade Agreement. These agreements undermine health-based national pesticide registration requirements; weaken health ministries' role in pesticide control; block marketing of cheaper, less toxic pesticides; and have a chilling effect on future pesticide regulatory activity. So long as corporations have privileged access to the trade negotiations and civil society is excluded, the resulting agreements will benefit special interests at the expense of public health.
Wu, Yuqing; Wang, Ke; Tan, Haiying; Xu, Jiangping; Zhu, Jintao
2017-09-26
A simple yet efficient method is developed to manipulate the self-assembly of pH-sensitive block copolymers (BCPs) confined in emulsion droplets. Addition of acid induces significant variation in morphological transition (e.g., structure and surface composition changes) of the polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) assemblies, due to the hydrophobic-hydrophilic transition of the pH-sensitive P4VP block via protonation. In the case of pH > pKa (P4VP) (pKa (P4VP) = 4.8), the BCPs can self-assemble into pupa-like particles because of the nearly neutral wetting of PS and P4VP blocks at the oil/water interface. As expected, onion-like particles obtained when pH is slightly lower than pKa (P4VP) (e.g., pH = 3.00), due to the interfacial affinity to the weakly hydrophilic P4VP block. Interestingly, when pH was further decreased to ∼2.5, interfacial instability of the emulsion droplets was observed, and each emulsion droplet generated nanoscale assemblies including vesicles, worm-like and/or spherical micelles rather than a nanostructured microparticle. Furthermore, homopolymer with different molecular weights and addition ratio are employed to adjust the interactions among copolymer blocks. By this means, particles with hierarchical structures can be obtained. Moreover, owing to the kinetically controlled processing, we found that temperature and stirring speed, which can significantly affect the kinetics of the evaporation of organic solvent and the formation of particles, played a key role in the morphology of the assemblies. We believe that manipulation of the property for the aqueous phase is a promising strategy to rationally design and fabricate polymeric assemblies with desirable shapes and internal structures.
NASA Astrophysics Data System (ADS)
Ikemoto, Toshikazu; Mori, Masashi; Miyajima, Masakatsu; Hashimoto, Takao; Murata, Akira
There are many earthquake damages of kenchi block masonry wall. So, we carried out experimental studies on the collapse mechanism of kenchi block masonry wall during earthquake. From these experimental data, i.e. acceleration response magnification, displacement and soil pressure were found to destroy the central wall vibrations caused by the subsidence of the embankment.
Paleogene volcanism in Central Afghanistan: Possible far-field effect of the India-Eurasia collision
NASA Astrophysics Data System (ADS)
Motuza, Gediminas; Šliaupa, Saulius
2017-10-01
A volcanic-sedimentary succession of Paleogene age is exposed in isolated patches at the southern margin of the Tajik block in the Ghor province of Central Afghanistan. The volcanic rocks range from basalts and andesites to dacites, including adakites. They are intercalated with sedimentary rocks deposited in shallow marine environments, dated biostratigraphically as Paleocene-Eocene. This age corresponds to the age of the Asyābēd andesites located in the western Ghor province estimated by the 40Ar/39Ar method as 54 Ma. The magmatism post-dates the Cimmerian collision between the Tajik block (including the Band-e-Bayan block) and the Farah Rod block located to the south. While the investigated volcanic rocks apparently bear geochemical signatures typical to an active continental margin environment, it is presumed that the magmatism was related to rifting processes most likely initiated by far-field tectonics caused by the terminal collision of the Indian plate with Eurasia (Najman et al., 2017). This event led to the dextral movement of the Farah Rod block, particularly along Hari Rod (Herat) fault system, resulting in the development of a transtensional regime in the proximal southern margin of the Tajik block and giving rise to a rift basin where marine sediments were interbedded with pillow lavas intruded by sheeted dyke series.
SEM analysis of ionizing radiation effects in an analog to digital converter /AD571/
NASA Technical Reports Server (NTRS)
Gauthier, M. K.; Perret, J.; Evans, K. C.
1981-01-01
The considered investigation is concerned with the study of the total-dose degradation mechanisms in an IIL analog to digital (A/D) converter. The A/D converter is a 10 digit device having nine separate functional units on the chip which encompass several hundred transistors and circuit elements. It was the objective of the described research to find the radiation sensitive elements by a systematic search of the devices on the LSI chip. The employed technique using a scanning electron microscope to determine the functional blocks of an integrated circuit which are sensitive to ionizing radiation and then progressively zeroing in on the soft components within those blocks, proved extremely successful on the AD571. Four functional blocks were found to be sensitive to radiation, including the Voltage Reference, DAC, IIL Clock, and IIL SAR.
NASA Astrophysics Data System (ADS)
Rea-Downing, G.; Lippert, P. C.; Stearns, M.
2017-12-01
The Alxa block is positioned between the western North China Craton (NCC) to the east and the Tarim Craton to the west. Several first-order characteristics of the Alxa region remain largely unresolved due to the limited outcrop exposure and remote nature of the region. For example, the crustal affinity and thermo-tectonic history of the Alxa block throughout Central Asian terrane accretion may have pre-conditioned the Cenozoic and Recent strain. Recent paleomagnetic and detrital zircon studies within the Alxa block indicate that its basement geology and apparent polar wander path are substantially different from the NCC. These data suggest that Alxa was not initially part of the NCC. Identification of a suture between Alxa and the NCC, timing of the incorporation of the Alxa block with the NCC, and the correlation of well-studied tectono-thermal events occurring in the NCC to the comparatively understudied Alxa block to the west are poorly constrained. Preliminary petrochronologic data from granitoid bodies within the Langshan range address these limitations by characterizing the bedrock age and affinity along the NE edge of the Alxa block. LA-Q-ICP-MS analysis of zircons including U-Pb dates, major and minor trace elemental data, and rare earth element compositions are combined with bulk rock geochemistry to place early-mid Carboniferous ( 350 Ma) Langshan plutons in a regional context. The relative rarity of plutons of this age in a region replete with Permo-Triassic plutonism indicates that the Langshan includes a record of relatively understudied magmatism along the periphery of the NCC. The approach utilized here allows for 1) direct age and compositional comparisons to other Carboniferous-Permian plutons in central Asia and 2) a robust provenance data point for future detrital zircon studies of the Paleozoic paleogeography in the heart of Central Asia.
Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers
2017-01-01
Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block. PMID:28994585
Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers.
van Genabeek, Bas; Lamers, Brigitte A G; de Waal, Bas F M; van Son, Martin H C; Palmans, Anja R A; Meijer, E W
2017-10-25
Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.
NASA Astrophysics Data System (ADS)
Gürer, Derya; van Hinsbergen, Douwe J. J.; Özkaptan, Murat; Creton, Iverna; Koymans, Mathijs R.; Cascella, Antonio; Langereis, Cornelis G.
2018-03-01
To quantitatively reconstruct the kinematic evolution of Central and Eastern Anatolia within the framework of Neotethyan subduction accommodating Africa-Eurasia convergence, we paleomagnetically assess the timing and amount of vertical axis rotations across the Ulukışla and Sivas regions. We show paleomagnetic results from ˜ 30 localities identifying a coherent rotation of a SE Anatolian rotating block comprised of the southern Kırşehir Block, the Ulukışla Basin, the Central and Eastern Taurides, and the southern part of the Sivas Basin. Using our new and published results, we compute an apparent polar wander path (APWP) for this block since the Late Cretaceous, showing that it experienced a ˜ 30-35° counterclockwise vertical axis rotation since the Oligocene time relative to Eurasia. Sediments in the northern Sivas region show clockwise rotations. We use the rotation patterns together with known fault zones to argue that the counterclockwise-rotating domain of south-central Anatolia was bounded by the Savcılı Thrust Zone and Deliler-Tecer Fault Zone in the north and by the African-Arabian trench in the south, the western boundary of which is poorly constrained and requires future study. Our new paleomagnetic constraints provide a key ingredient for future kinematic restorations of the Anatolian tectonic collage.
Walton, James C.; Waxman, Brandon; Hoffbuhr, Kristen; Kennedy, Meaghan; Beth, Ellen; Scangos, Jennifer; Thompson, Richmond R.
2013-01-01
We have previously demonstrated that centrally administered vasotocin (VT) inhibits social approach toward same-sex conspecifics in male and female goldfish, and that this behavioral effect is dependent upon VT projections to the hindbrain. We now show that there are no sex differences in sensitivity to the behavioral effects of VT, though differences do exist in responsiveness across seasons in both sexes. A central dose of 1 µg, but not 200 ng, inhibited social approach in goldfish in non-reproductive condition, whereas a dose as low as 40 ng inhibited social approach in fish in full reproductive condition. In males and females in full reproductive condition, social approach behavior was facilitated by central administration of 500 ng of a V1A specific antagonist. In addition, the behavioral effects of exogenously administered central VT were blocked by central administration of 1 µg of a V1A antagonist. These results demonstrate that the propensity to approach a conspecific, a simple behavior underlying many social interactions, is controlled by a V1A-like receptor, and that VT’s behavioral effects depend on reproductive context. Quantitative real-time PCR showed that the seasonal changes in behavioral responsiveness to VT are associated with changes in the expression of a V1A-like receptor in the hindbrain, but not the mid- or forebrain, indicating that the seasonal regulation of social approach behavior likely depends on the local modulation of the expression of this receptor within a primitive peptide circuit in this species. PMID:19616564
CENTRAL REINFORCING EFFECTS OF ETHANOL ARE BLOCKED BY CATALASE INHIBITION
Nizhnikov, Michael Edward; Molina, Juan Carlos; Spear, Norman
2007-01-01
Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol’s positive reinforcing effects. Central administrations of ethanol (25–200 mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn’s response to a surrogate nipple scented with the CS. It has been shown that ethanol’s first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous system. A significant amount of acetaldehyde is derived from ethanol metabolism via the catalase system. In newborn rats catalase levels are particularly high in several brain structures. The present study tested the effect of catalase inhibition on central ethanol reinforcement. In the first experiment, pups experienced lemon odor either paired or unpaired with intracisternal (i.c.) administrations of 100 mg% ethanol. Half of the animals corresponding to each learning condition were pretreated with i.c. administrations of either physiological saline or a catalase inhibitor (sodium-azide). Catalase inhibition completely suppressed ethanol reinforcement in paired groups without affecting responsiveness to the CS during conditioning or responding by unpaired control groups. A second experiment tested whether these effects were specific to ethanol reinforcement or due instead to general impairment in learning and expression capabilities. Central administration of an endogenous kappa opioid receptor agonist (dynorphin A-13) was employed as an alternative source of reinforcement. Inhibition of the catalase system had no effect on the reinforcing properties of dynorphin. The present results support the hypothesis that ethanol metabolism regulated by the catalase system plays a critical role in determination of ethanol reinforcement in newborn rats. PMID:17980789
Classical conformal blocks and accessory parameters from isomonodromic deformations
NASA Astrophysics Data System (ADS)
Lencsés, Máté; Novaes, Fábio
2018-04-01
Classical conformal blocks appear in the large central charge limit of 2D Virasoro conformal blocks. In the AdS3 /CFT2 correspondence, they are related to classical bulk actions and used to calculate entanglement entropy and geodesic lengths. In this work, we discuss the identification of classical conformal blocks and the Painlevé VI action showing how isomonodromic deformations naturally appear in this context. We recover the accessory parameter expansion of Heun's equation from the isomonodromic τ -function. We also discuss how the c = 1 expansion of the τ -function leads to a novel approach to calculate the 4-point classical conformal block.
The tectonic evolution of western Central Iran seen through detrital white mica
NASA Astrophysics Data System (ADS)
Kargaranbafghi, Fariba; Neubauer, Franz; Genser, Johann
2015-05-01
A first order survey of 40Ar/39Ar dating of detrital white mica from Jurassic to Pliocene sandstones has been carried out in order to reveal the tectonic evolution of blocks in Central Iran. The Central Iran block was believed to represent a stable Precambrian block. Our results indicate that: (1) Only a very small proportion of Precambrian but abundant Paleozoic and Mesozoic detrital white mica indicate the Phanerozoic, mostly Mesozoic age of metamorphic crust exposed in Central Iran. The oldest but scarce detrital white mica grains have ages ranging from 524 to 826 Ma heralding a Late Precambrian and Cambrian crystalline basement or cannibalism from older clastic successions. (2) Jurassic and Cretaceous sandstones from the west and east of the Chapedony fault yield different age spectra, with a dominance of Variscan ages (ca. 308-385 Ma) in the Biabanak unit west of the Chapedony fault compared to coeval sandstones from the block east of the Chapedony fault, where Variscan ages are subordinate and Cimmerian ages predominate. The micas from the Biabanak unit are most likely derived from the Variscan accretionary complex exposed in the Anarak-Jandaq areas further northwest. This result underlines the importance of a major block boundary identified as the Chapedony fault, which is in extension of a fault previously proposed. (3) Two stages of Cimmerian events are visible in our data set from Cretaceous and Paleogene sandstones, a cluster around 170 Ma and at ca. 205 Ma. These clusters suggest a two-stage Cimmerian evolution of the largely amphibolite-grade metamorphic Posht-e-Badam and Boneh Shurow complexes. (4) The youngest micas in Paleogene conglomerates have an age of ca. 100 Ma and are most likely derived from the base of the Posht-e-Badam complex. No record of the uplifted Eocene Chapedony metamorphic core complex has been found in Eocene and Pliocene clastic rocks.
From global to heavy-light: 5-point conformal blocks
NASA Astrophysics Data System (ADS)
Alkalaev, Konstantin; Belavin, Vladimir
2016-03-01
We consider Virasoro conformal blocks in the large central charge limit. There are different regimes depending on the behavior of the conformal dimensions. The most simple regime is reduced to the global sl(2,C) conformal blocks while the most complicated one is known as the classical conformal blocks. Recently, Fitzpatrick, Kaplan, and Walters showed that the two regimes are related through the intermediate stage of the so-called heavy-light semiclassical limit. We study this idea in the particular case of the 5-point conformal block. To find the 5-point global block we use the projector technique and the Casimir operator approach. Furthermore, we discuss the relation between the global and the heavy-light limits and construct the heavy-light block from the global block. In this way we reproduce our previous results for the 5-point perturbative classical block obtained by means of the monodromy method.
Pru p 3, a marker allergen for lipid transfer protein sensitization also in Central Europe.
Mothes-Luksch, N; Raith, M; Stingl, G; Focke-Tejkl, M; Razzazi-Fazeli, E; Zieglmayer, R; Wöhrl, S; Swoboda, I
2017-09-01
In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant-food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract-based diagnosis is often complicated by co-sensitization to Bet v 1, the major birch pollen allergen, its cross-reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant-derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant-food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients. © 2017 The Authors Allergy Published by John Wiley & Sons Ltd.
Ribeiro, Antonio L; Sabino, Ester C; Marcolino, Milena S; Salemi, Vera M C; Ianni, Barbara M; Fernandes, Fábio; Nastari, Luciano; Antunes, André; Menezes, Márcia; Oliveira, Cláudia Di Lorenzo; Sachdev, Vandana; Carrick, Danielle M; Busch, Michael P; Murphy, Eduard L
2013-01-01
Blood donor screening leads to large numbers of new diagnoses of Trypanosoma cruzi infection, with most donors in the asymptomatic chronic indeterminate form. Information on electrocardiogram (ECG) findings in infected blood donors is lacking and may help in counseling and recognizing those with more severe disease. To assess the frequency of ECG abnormalities in T.cruzi seropositive relative to seronegative blood donors, and to recognize ECG abnormalities associated with left ventricular dysfunction. The study retrospectively enrolled 499 seropositive blood donors in São Paulo and Montes Claros, Brazil, and 483 seronegative control donors matched by site, gender, age, and year of blood donation. All subjects underwent a health clinical evaluation, ECG, and echocardiogram (Echo). ECG and Echo were reviewed blindly by centralized reading centers. Left ventricular (LV) dysfunction was defined as LV ejection fraction (EF)<0.50%. Right bundle branch block and left anterior fascicular block, isolated or in association, were more frequently found in seropositive cases (p<0.0001). Both QRS and QTc duration were associated with LVEF values (correlation coefficients -0.159,p<0.0003, and -0.142,p = 0.002) and showed a moderate accuracy in the detection of reduced LVEF (area under the ROC curve: 0.778 and 0.790, both p<0.0001). Several ECG abnormalities were more commonly found in seropositive donors with depressed LVEF, including rhythm disorders (frequent supraventricular ectopic beats, atrial fibrillation or flutter and pacemaker), intraventricular blocks (right bundle branch block and left anterior fascicular block) and ischemic abnormalities (possible old myocardial infarction and major and minor ST abnormalities). ECG was sensitive (92%) for recognition of seropositive donors with depressed LVEF and had a high negative predictive value (99%) for ruling out LV dysfunction. ECG abnormalities are more frequent in seropositive than in seronegative blood donors. Several ECG abnormalities may help the recognition of seropositive cases with reduced LVEF who warrant careful follow-up and treatment.
Numerical modelling of distributed vibration sensor based on phase-sensitive OTDR
NASA Astrophysics Data System (ADS)
Masoudi, A.; Newson, T. P.
2017-04-01
A Distributed Vibration Sensor Based on Phase-Sensitive OTDR is numerically modeled. The advantage of modeling the building blocks of the sensor individually and combining the blocks to analyse the behavior of the sensing system is discussed. It is shown that the numerical model can accurately imitate the response of the experimental setup to dynamic perturbations a signal processing procedure similar to that used to extract the phase information from sensing setup.
Mason, Bianca N.; Kaiser, Eric A.; Kuburas, Adisa; Loomis, Maria-Cristina M.; Latham, John A.; Garcia-Martinez, Leon F.
2017-01-01
The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. SIGNIFICANCE STATEMENT The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms. PMID:28053042
Peterson, Daniel J; Gill, W Drew; Dose, John M; Hoover, Donald B; Pauly, James R; Cummins, Elizabeth D; Burgess, Katherine C; Brown, Russell W
2017-05-15
Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking. Copyright © 2017. Published by Elsevier B.V.
Peterson, Daniel J.; Gill, W. Drew; Dose, John M.; Hoover, Donald B.; Pauly, James R.; Cummins, Elizabeth D.; Burgess, Katherine C.; Brown, Russell W.
2017-01-01
Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given ip injections of either saline or nicotine (0.5 mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4 mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3 mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not 7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking. PMID:28235586
Murata, Yoshimichi; Fujiwara, Yuichiro; Kubo, Yoshihiro
2002-01-01
The inward rectifier potassium channel Kir2.1 is more sensitive to the weakly voltage-dependent block by extracellular Mg2+ (Mg02+) than Kir2.2 and Kir2.3. We identified Glu125 in an extracellular loop before the pore region of Kir2.1 as a site responsible for this sensitivity to M02+ block, based on the observations that the Glu125Gln (E125Q) mutation strongly decreased the sensitivity, while a mutation to Glu at the corresponding sites of Kir2.2 and 2.3 led to an increase. The negative charge proved to be crucial since the Glu125Asp (E125D) mutant showed similar properties to the wild type (WT). A similar weakly voltage-dependent block was also caused by extracellular Ca2+ and La3+ in Kir2.1 WT but not in the E125Q mutant. The sensitivity to block by extracellular Ba2+ (Ba02+) was also decreased in the E125Q mutant, although the voltage dependency of half-inhibition concentration was not changed, as reported previously. We additionally observed that the speed of Ba02+ block and recovery was decelerated by the presence of Mg02+ in WT, but not in the E125Q mutant. The sensitivity to the block by Mg02+ was increased by lowering extracellular K+ (K0+), suggesting a competitive interaction of Mg02+ and K0+. The single-channel conductance of the WT in 140 mm K+ was 39.6 pS (0 mm Mg02+) and 11.5 pS (10 mm), while that of the E125Q mutant was 26.0 pS (0 mm) and 19.6 pS (10 mm). These results demonstrate that Mg2+ competes with K+ permeation in the WT and that E125 is required for efficient K+ permeation in the absence of Mg02+. We conclude that E125 in an extracellular loop of Kir2.1 is a site which facilitates K+ permeation and entry of Ba2+ toward a deeper plugging site, and that Mg02+ competes with K0+ and Ba02+ at this site. PMID:12411513
NASA Astrophysics Data System (ADS)
Song, Peiping; Ding, Lin; Li, Zhenyu; Lippert, Peter C.; Yang, Tianshui; Zhao, Xixi; Fu, Jiajun; Yue, Yahui
2015-08-01
To better constrain the Late Triassic paleolatitude of the Qiangtang block and the closure of the Paleo-Tethys Ocean, a combined paleomagnetic and zircon U/Pb geochronological study has been conducted on the Upper Triassic Jiapila Formation volcanic rocks on the northern edge of the Qiangtang block of Central Tibet (34.1°N, 92.4°E). These rocks are dated to 204-213 Ma. Progressive thermal or alternating field demagnetization successfully isolated stable characteristic remanent magnetizations (ChRM) that pass both the fold and reversal tests, consistent with a primary magnetization. These are the first volcanic-based paleomagnetic results from pre-Cretaceous rocks of the Qiangtang block that appear to average secular variation well enough to yield a reliable paleolatitude estimate. Based on our new paleomagnetic data from Upper Triassic lavas, we conclude that the Late Triassic pole of the Qiangtang block was located at 64.0°N, 174.7°E, with A95 = 6.6 ° (N = 29). We compile published paleomagnetic data from the Qiangtang block to calculate a Late Triassic latitude for the Qiangtang block at 31.7 ± 3.0°N. The central Paleo-Tethys Ocean basin was located between the North China (NCB) and Tarim blocks to the north and the Qiangtang block to the south during Late Paleozoic-Early Mesozoic. A comparison of published Early Triassic paleopole from the Qiangtang block with the coeval paleopoles from the NCB and Tarim indicates that the Paleo-Tethys Ocean could not have closed during the Early Triassic and that its width was approximately ∼32-38° latitude (∼3500-4200 km). However, the comparison of our new combined Late Triassic paleomagnetic result with the Late Triassic poles of the NCB and Tarim, as well as numerous geological observations, indicates that the closure of the Paleo-Tethys Ocean at the longitude of the Qiangtang block most likely occurred during the Late Triassic.
Patel, Sunit M; Ebenezer, Ivor S
2004-10-25
In order to test the hypothesis that endogenous gamma-aminobutyric acid (GABA), acting at central GABAB receptors, plays a physiological role in the control of feeding behaviour, it was reasoned that blocking these receptors with a centrally active GABAB receptor antagonist should reduce food intake in hungry rats. In the present study, experiments were carried out to test this possibility using the GABAB receptor antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid (CGP 35348), which is water-soluble and can penetrate the blood-brain barrier from the systemic circulation. CGP 35348 (50 and 100 mg/kg, i.p.) had no effect on food intake in 22-h fasted rats, but a higher dose (i.e. 500 mg/kg., i.p.) significantly reduced cumulative food consumption. These findings are consistent with previous observations that high systemic doses of CGP 35348 are needed to block central GABAB receptors. However, to eliminate the possibility that the 500 mg/kg dose of CGP 35348 decreased food intake by a peripheral, rather than a central mode of action, further experiments were undertaken where the drug was given directly into the brain by the intracerebroventricular (i.c.v.) route. I.c.v. administration of CGP 35348 (5 and 10 microg) significantly decreased cumulative food intake food intake in rats that had been fasted for 22 h. By contrast, i.c.v. administration of CGP 35348 (10 microg) had no effect on water intake in 16-h water-deprived rats. The results indicate that CGP 35348 reduces food consumption in hungry rats by blocking central GABAB receptors in a behaviourally specific manner. These findings suggest that endogenous GABA acting at central GABAB receptors plays a physiological role in the regulation of feeding behaviour.
Long, E.; Ashley, J.W.
1958-12-16
A graphite moderator structure is described for a gas-cooled nuclear reactor having a vertical orlentation wherein the structure is physically stable with regard to dlmensional changes due to Wigner growth properties of the graphite, and leakage of coolant gas along spaces in the structure is reduced. The structure is comprised of stacks of unlform right prismatic graphite blocks positioned in layers extending in the direction of the lengths of the blocks, the adjacent end faces of the blocks being separated by pairs of tiles. The blocks and tiles have central bores which are in alignment when assembled and are provided with cooperatlng keys and keyways for physical stability.
Nieuwveld, D; Mojica, V; Herrera, A E; Pomés, J; Prats, A; Sala-Blanch, X
2017-04-01
Ultrasound-guided infraclavicular block in the costoclavicular space located between the clavicle and the first rib, reaches the secondary trunks when they are clustered together and lateral to the axillary artery. This block is most often performed through a lateral approach, the difficulty being finding the coracoid process an obstacle and guiding the needle towards the vessels and pleura. A medial approach, meaning from inside to outside, will avoid these structures. Traditionally the assessment of a successful block is through motor or sensitive responses but a sympathetic fibre block can also be evaluated measuring the changes in humeral artery blood flow, skin temperature and/or perfusion index. To describe the medial approach of the ultrasound-guided costoclavicular block evaluating its development by motor and sensitive response and measurement of sympathetic changes. Description of the technique and administration of 20ml of contrast in a fresh cadaver model, evaluating the distribution with CT-scan and sagittal sections of the anatomic piece. Subsequently in a clinical phase, including 11 patients, we evaluated the establishment of motor, sensitive and sympathetic blocks. We evaluated the sympathetic changes reflected by humeral artery blood flow, skin temperature and distal perfusion index. In the anatomical model the block was conducted without difficulties, showing an adequate periclavicular distribution of the contrast in the CT-scan and in sagittal sections, reaching the interscalenic space as far as the secondary trunks. Successful blocks were observed in 91% of patients after 25minutes. All the parameters reflecting sympathetic block increased significantly. The humeral artery blood flow showed an increase from 108 ± 86 to 188±141ml/min (P=.05), skin temperature from 32.1±2 to 32.8±9°C (P=.03) and perfusion index from 4±3 to 9±5 (P=.003). The medial approach of the ultrasound-guided costoclavicular block is anatomically feasible, with high clinical effectiveness using 20ml of 1.5% mepivacaine. The sympathetic block can be evaluated with all three parameters studied. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
NASA Technical Reports Server (NTRS)
Atkins, Harold
1991-01-01
A multiple block multigrid method for the solution of the three dimensional Euler and Navier-Stokes equations is presented. The basic flow solver is a cell vertex method which employs central difference spatial approximations and Runge-Kutta time stepping. The use of local time stepping, implicit residual smoothing, multigrid techniques and variable coefficient numerical dissipation results in an efficient and robust scheme is discussed. The multiblock strategy places the block loop within the Runge-Kutta Loop such that accuracy and convergence are not affected by block boundaries. This has been verified by comparing the results of one and two block calculations in which the two block grid is generated by splitting the one block grid. Results are presented for both Euler and Navier-Stokes computations of wing/fuselage combinations.
Conformal blocks from Wilson lines with loop corrections
NASA Astrophysics Data System (ADS)
Hikida, Yasuaki; Uetoko, Takahiro
2018-04-01
We compute the conformal blocks of the Virasoro minimal model or its WN extension with large central charge from Wilson line networks in a Chern-Simons theory including loop corrections. In our previous work, we offered a prescription to regularize divergences from loops attached to Wilson lines. In this paper, we generalize our method with the prescription by dealing with more general operators for N =3 and apply it to the identity W3 block. We further compute general light-light blocks and heavy-light correlators for N =2 with the Wilson line method and compare the results with known ones obtained using a different prescription. We briefly discuss general W3 blocks.
High frequency ultrasound imaging in pupillary block glaucoma.
Aslanides, I M; Libre, P E; Silverman, R H; Reinstein, D Z; Lazzaro, D R; Rondeau, M J; Harmon, G K; Coleman, D J
1995-01-01
BACKGROUND--The diagnosis of pupillary block glaucoma requires sufficient clarity of the ocular media. This is particularly important for assessment of both the presence and patency of an iridotomy, and the determination of central anterior chamber depth. METHODS--High frequency ultrasonography was used in three patients with suspected pupillary block to determine iris configuration, posterior chamber volume, and ciliary body conformation. RESULTS--All patients demonstrated high frequency ultrasonographic findings consistent with pupillary block: iris bombé, a formed posterior chamber, and a lack of anterior rotation of the ciliary processes. CONCLUSION--High frequency ultrasound imaging appears to be a valuable adjunct in making or corroborating the diagnosis of pupillary block glaucoma. Images PMID:8534666
77 FR 6657 - Blocking Property of the Government of Iran and Iranian Financial Institutions
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-08
... Property of the Government of Iran and Iranian Financial Institutions #0; #0; #0; Presidential Documents #0... Blocking Property of the Government of Iran and Iranian Financial Institutions By the authority vested in... the Central Bank of Iran and other Iranian banks to conceal transactions of sanctioned parties, the...
A bird's eye view of "Understanding volcanoes in the Vanuatu arc"
NASA Astrophysics Data System (ADS)
Vergniolle, S.; Métrich, N.
2016-08-01
The Vanuatu intra-oceanic arc, located between 13 and 22°S in the southwest Pacific Ocean (Fig. 1), is one of the most seismically active regions with almost 39 earthquakes magnitude 7 + in the past 43 years (Baillard et al., 2015). Active deformation in both the Vanuatu subduction zone and the back-arc North-Fiji basin accommodates the variation of convergence rates which are c.a. 90-120 mm/yr along most of the arc (Taylor et al., 1995; Pelletier et al., 1998). The convergence rate is slowed down to 25-43 mm/yr (Baillard et al., 2015) in the central segment where the D'Entrecasteaux ridge - an Eocene-Oligocene island arc complex on the Australian subducting plate - collides and is subducted beneath the fore-arc (Taylor et al., 2005). Hence, the Vanuatu arc is segmented in three blocks which move independently; as the north block rotates counter-clockwise in association with rapid back-arc spreading ( 80 mm/year), the central block translates eastward and the south block rotates clockwise (Calmant et al., 2003; Bergeot et al., 2009). (See Fig. 1.)
Topuz, Bora B; Altinbas, Burcin; Yilmaz, Mustafa S; Saha, Sikha; Batten, Trevor F; Savci, Vahide; Yalcin, Murat
2014-05-01
CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. İ.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway. Copyright © 2014 Elsevier B.V. All rights reserved.
Radiation tolerant combinational logic cell
NASA Technical Reports Server (NTRS)
Maki, Gary R. (Inventor); Whitaker, Sterling (Inventor); Gambles, Jody W. (Inventor)
2009-01-01
A system has a reduced sensitivity to Single Event Upset and/or Single Event Transient(s) compared to traditional logic devices. In a particular embodiment, the system includes an input, a logic block, a bias stage, a state machine, and an output. The logic block is coupled to the input. The logic block is for implementing a logic function, receiving a data set via the input, and generating a result f by applying the data set to the logic function. The bias stage is coupled to the logic block. The bias stage is for receiving the result from the logic block and presenting it to the state machine. The state machine is coupled to the bias stage. The state machine is for receiving, via the bias stage, the result generated by the logic block. The state machine is configured to retain a state value for the system. The state value is typically based on the result generated by the logic block. The output is coupled to the state machine. The output is for providing the value stored by the state machine. Some embodiments of the invention produce dual rail outputs Q and Q'. The logic block typically contains combinational logic and is similar, in size and transistor configuration, to a conventional CMOS combinational logic design. However, only a very small portion of the circuits of these embodiments, is sensitive to Single Event Upset and/or Single Event Transients.
Renyi entropy for local quenches in 2D CFT from numerical conformal blocks
NASA Astrophysics Data System (ADS)
Kusuki, Yuya; Takayanagi, Tadashi
2018-01-01
We study the time evolution of Renyi entanglement entropy for locally excited states in two dimensional large central charge CFTs. It generically shows a logarithmical growth and we compute the coefficient of log t term. Our analysis covers the entire parameter regions with respect to the replica number n and the conformal dimension h O of the primary operator which creates the excitation. We numerically analyse relevant vacuum conformal blocks by using Zamolodchikov's recursion relation. We find that the behavior of the conformal blocks in two dimensional CFTs with a central charge c, drastically changes when the dimensions of external primary states reach the value c/32. In particular, when h O ≥ c/32 and n ≥ 2, we find a new universal formula Δ {S}_A^{(n)}˜eq nc/24(n-1) log t. Our numerical results also confirm existing analytical results using the HHLL approximation.
Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats.
Škrbić, Ranko; Stojiljković, Miloš P; Ćetković, Slavko S; Dobrić, Silva; Jeremić, Dejan; Vulović, Maja
2017-06-01
The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve-diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose-dependently antagonized the soman-induced respiratory blockade. Atropine, at a dose that was per se ineffective in counteracting soman-induced respiratory depression, potentiated the protective effects of naloxone and completely restored respiration. Naloxone remained completely ineffective in antagonizing respiratory depression induced by the muscarinic receptor agonist the oxotremorine. It is assumed that naloxone antagonizes soman-induced respiratory inhibition by blocking endogenous opioidergic respiratory control pathways that are independent of the stimulation of muscarinic receptors. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Lluch, Enrique; Nijs, Jo; Courtney, Carol A; Rebbeck, Trudy; Wylde, Vikki; Baert, Isabel; Wideman, Timothy H; Howells, Nick; Skou, Søren T
2017-08-02
Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice. The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice. A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors. It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense. This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies. Implications for Rehabilitation Laboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice. A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed. Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.
The First Row Anomaly and Recoupled Pair Bonding in the Halides of the Late p-Block Elements
2012-01-01
The dramatic differences between the properties of molecules formed from the late p-block elements of the first row of the periodic table (N–F) and those of the corresponding elements in subsequent rows is well recognized as the first row anomaly. Certain properties of the atoms, such as the relative energies and spatial extents of the ns and np orbitals, can explain some of these differences, but not others. In this Account, we summarize the results of our recent computational studies of the halides of the late p-block elements. Our studies point to a single underlying cause for many of these differences: the ability of the late p-block elements in the second and subsequent rows of the periodic table to form recoupled pair bonds and recoupled pair bond dyads with very electronegative ligands. Recoupled pair bonds form when an electron in a singly occupied ligand orbital recouples the pair of electrons in a doubly occupied lone pair orbital on the central atom, leading to a central atom-ligand bond. Recoupled pair bond dyads occur when a second ligand forms a bond with the orbital left over from the initial recoupled pair bond. Recoupled pair bonds and recoupled pair bond dyads enable the late p-block elements to form remarkably stable hypervalent compounds such as PF5 and SF6 and lead to unexpected excited states in smaller halides of the late p-block elements such as SF and SF2. Recoupled pair bonding also causes the Fn–1X–F bond energies to oscillate dramatically once the normal valences of the central atoms have been satisfied. In addition, recoupled pair bonding provides a lower-energy pathway for inversion in heavily fluorinated compounds (PF3 and PF2H, but not PH2F and PH3) and leads to unusual intermediates and products in reactions involving halogens and late p-block element compounds, such as (CH3)2S + F2. Although this Account focuses on the halides of the second row, late p-block elements, recoupled pair bonds and recoupled pair bond dyads are important in the chemistry of p-block elements beyond the second row (As, Se, and Br) and for compounds of these elements with other very electronegative ligands, such as OH and O. Knowledge of recoupled pair bonding is thus critical to understanding the properties and reactivity of molecules containing the late p-block elements beyond the first row. PMID:23151313
The first row anomaly and recoupled pair bonding in the halides of the late p-block elements.
Dunning, Thom H; Woon, David E; Leiding, Jeff; Chen, Lina
2013-02-19
The dramatic differences between the properties of molecules formed from the late p-block elements of the first row of the periodic table (N-F) and those of the corresponding elements in subsequent rows is well recognized as the first row anomaly. Certain properties of the atoms, such as the relative energies and spatial extents of the ns and np orbitals, can explain some of these differences, but not others. In this Account, we summarize the results of our recent computational studies of the halides of the late p-block elements. Our studies point to a single underlying cause for many of these differences: the ability of the late p-block elements in the second and subsequent rows of the periodic table to form recoupled pair bonds and recoupled pair bond dyads with very electronegative ligands. Recoupled pair bonds form when an electron in a singly occupied ligand orbital recouples the pair of electrons in a doubly occupied lone pair orbital on the central atom, leading to a central atom-ligand bond. Recoupled pair bond dyads occur when a second ligand forms a bond with the orbital left over from the initial recoupled pair bond. Recoupled pair bonds and recoupled pair bond dyads enable the late p-block elements to form remarkably stable hypervalent compounds such as PF(5) and SF(6) and lead to unexpected excited states in smaller halides of the late p-block elements such as SF and SF(2). Recoupled pair bonding also causes the F(n-1)X-F bond energies to oscillate dramatically once the normal valences of the central atoms have been satisfied. In addition, recoupled pair bonding provides a lower-energy pathway for inversion in heavily fluorinated compounds (PF(3) and PF(2)H, but not PH(2)F and PH(3)) and leads to unusual intermediates and products in reactions involving halogens and late p-block element compounds, such as (CH(3))(2)S + F(2). Although this Account focuses on the halides of the second row, late p-block elements, recoupled pair bonds and recoupled pair bond dyads are important in the chemistry of p-block elements beyond the second row (As, Se, and Br) and for compounds of these elements with other very electronegative ligands, such as OH and O. Knowledge of recoupled pair bonding is thus critical to understanding the properties and reactivity of molecules containing the late p-block elements beyond the first row.
Tailoring the sensitivity of initiating explosives
NASA Astrophysics Data System (ADS)
Manner, Virginia W.; Preston, Daniel N.; Snyder, Christopher J.; Dattelbaum, Dana M.; Tappan, Bryce C.
2017-01-01
Pentaerythritol tetranitrate (PETN) is a very common nitrate ester explosive that has been widely studied due to its use in military and commercial explosives. Recent experimental work and calculations have shown that substituting the central carbon atom of PETN with a silicon atom results in an extremely sensitive contact explosive. We have attempted to develop PETN derivatives which are less sensitive, by attaching hydrogen, amino, and methyl groups to the central carbon atom, and substituting the central carbon atom (and one -CH2ONO2 group) with phosphorous oxide. We relate the handling sensitivity properties of each PETN derivative to its structure, and discuss the role of the central atom, oxygen balance, thermal stability, and inter- and intramolecular hydrogen bonding on impact sensitivity.
Vlemincx, Elke; Van Diest, Ilse; Van den Bergh, Omer
2016-10-15
Both animal and human research have revealed important associations between sighs and relief. Previously we argued to conceive of sighs as resetters which temporarily induce relief. The present study aimed to investigate the psychological and physiological relief effect of sighs by instructed deep breaths and spontaneous sighs compared to a control breathing maneuver. Participants completed three blocks of 40 trials during which uncertainty cues were followed by either safety cues followed by a positive picture, or danger cues followed by a negative picture. One block was presented without breathing instructions, two subsequent blocks with breathing instructions. During the presentation of the safety and danger cues, an instruction was given to either 'take a deep breath' or 'postpone the next inhalation for 2 s (breath hold). Continuously, participants rated relief and Frontalis electromyography was recorded. Trait anxiety sensitivity was assessed by the Anxiety Sensitivity Index. Self-reported relief and physiological tension were compared 5s before and after instructed deep breaths and breath holds, and before and after spontaneous deep breaths and breath holds in the respective blocks. Results show that self-reported relief following an instructed deep breath was higher than before. Physiological tension decreased following a spontaneous sigh in high anxiety sensitive persons and following a spontaneous breath hold in low anxiety sensitive persons. These results are the first to show that a deep breath relieves and, in anxiety sensitive persons, reduces physiological tension. These findings support the hypothesis that sighs are psychological and physiological resetters. Copyright © 2016 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
El Sachat, Alexandros; Meristoudi, Anastasia; Markos, Christos; Pispas, Stergios; Riziotis, Christos
2014-03-01
A low cost and low complexity optical detection method of proteins is presented by employing a detection scheme based on electrostatic interactions, and implemented by sensitization of a polymer optical fibers' (POF) surface by thin overlayers of properly designed sensitive copolymer materials with predesigned charges. This method enables the fast detection of proteins having opposite charge to the overlayer, and also the effective discrimination of differently charged proteins like lysozyme (LYS) and bovine serum albumin (BSA). As sensitive materials the block and the random copolymers of the same monomers were employed, namely the block copolymer poly(styrene-b-2vinylpyridine) (PS-b- P2VP) and the corresponding random copolymer poly(styrene-r-2vinylpyridine) (PS-r-P2VP), of similar composition and molecular weights. Results show systematically different response between the block and the random copolymers, although of the same order of magnitude, drawing thus important conclusions on their applications' techno-economic aspects given that they have significantly different associated manufacturing method and costs. The use of the POF platform, in combination with those adaptable copolymer sensing materials could lead to efficient low cost bio-detection schemes.
NASA Astrophysics Data System (ADS)
Joshi, Bhrigu; Adhikari, Sailesh; Bhalla, Suresh
2016-04-01
This paper presents a comparative study through the piezoelectric coupled field analysis mode of finite element method (FEM) on detection of damages of varying magnitude, encompassing three different types of structural materials, using piezo impedance transducers. An aluminum block, a concrete block and a steel block of dimensions 48×48×10 mm were modelled in finite element software ANSYS. A PZT patch of 10×10×0.3 mm was also included in the model as surface bonded on the block. Coupled field analysis (CFA) was performed to obtain the admittance signatures of the piezo sensor in the frequency range of 0-250 kHz. The root mean square deviation (RMSD) index was employed to quantify the degree of variation of the signatures. It was found that concrete exhibited deviation in the signatures only with the change of damping values. However, the other two materials showed variation in the signatures even with changes in density and elasticity values in a small portion of the specimen. The comparative study shows that the PZT patches are more sensitive to damage detection in materials with low damping and the sensitivity typically decreases with increase in the damping.
The origin and development of plains-type folds during the cretaceous in Central and western Kansas
Merriam, D.F.; Forster, A.
2000-01-01
Kansas is part of the Central Stable Region of North America. Structural movement on this part of the craton has been mainly the result of tectonism in nearby areas. Response to the outside tectonic forces, transmitted through the rigid Precambrian basement, has been vertical adjustment. Differential movement along an indigenous fault/fracture pattern in the basement created displaced blocks over which the later sediments were draped by differential compaction. After initial formation of this structural regimen in late Mississippian-early Pennsylvanian time, continued movement of the basement blocks gave rise to the plains-type folds so prevalent in the U.S. Midcontinent. The incremental movement continues through the late Paleozoic, Mesozoic, and Tertiary until today. This paper demonstrates the Cretaceous development of some of these structures in central and western Kansas.
NASA Astrophysics Data System (ADS)
Rood, Dylan H.; Burbank, Douglas W.; Herman, Scott W.; Bogue, Scott
2011-10-01
We use paleomagnetic data from Tertiary volcanic rocks to address the rates and timing of vertical-axis block rotations across the central Sierra Nevada-Walker Lane transition in the Bodie Hills, California/Nevada. Samples from the Upper Miocene (˜9 Ma) Eureka Valley Tuff suggest clockwise vertical-axis block rotations between NE-striking left-lateral faults in the Bridgeport and Mono Basins. Results in the Bodie Hills suggest clockwise rotations (R ± ΔR, 95% confidence limits) of 74 ± 8° since Early to Middle Miocene (˜12-20 Ma), 42 ± 11° since Late Miocene (˜8-9 Ma), and 14 ± 10° since Pliocene (˜3 Ma) time with no detectable northward translation. The data are compatible with a relatively steady rotation rate of 5 ± 2° Ma-1 (2σ) since the Middle Miocene over the three examined timescales. The average rotation rates have probably not varied by more than a factor of two over time spans equal to half of the total time interval. Our paleomagnetic data suggest that block rotations in the region of the Mina Deflection began prior to Late Miocene time (˜9 Ma), and perhaps since the Middle Miocene if rotation rates were relatively constant. Block rotation in the Bodie Hills is similar in age and long-term average rate to rotations in the Transverse Ranges of southern California associated with early transtensional dextral shear deformation. We speculate that the age of rotations in the Bodie Hills indicates dextral shear and strain accommodation within the central Walker Lane Belt resulting from coupling of the Pacific and North America plates.
Cellular Trojan horse based polymer nanoreactors with light-sensitive activity.
Baumann, Patric; Spulber, Mariana; Dinu, Ionel Adrian; Palivan, Cornelia G
2014-08-07
Stimulus-sensitive systems at the nanoscale represent ideal candidates for improving therapeutic and diagnostic approaches by producing rapid responses to the presence of specific molecules or conditions either by changing properties or by acting "on demand". Here we introduce an optimized light-sensitive nanoreactor based on encapsulation of a photosensitizer inside polymer vesicles to serve as an efficient source of reactive oxygen species (ROS) "on demand". Two types of amphiphilic block copolymers, poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline), PMOXA-PDMS-PMOXA, and poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N-vinylpyrrolidone), PNVP-PDMS-PNVP, were used to encapsulate Rose Bengal-bovine serum albumin (RB-BSA) inside the cavity of vesicles. The difference of copolymers molecular properties (hydrophobic to hydrophilic ratio, different chemical nature of the hydrophilic block) influenced the encapsulation ability, and uptake by cells, allowing therefore a selection of the most efficient polymer system. Nanoreactors were optimized in terms of (i) size, (ii) stability, and (iii) encapsulation efficiency based on a combination of light scattering, TEM, and UV-vis spectroscopy. By illumination, encapsulated RB-BSA conjugates generated in situ ROS, which diffused through the polymer membrane to the environment of the vesicles, as proved by electron spin resonance spectroscopy (ESR). Optimum illumination conditions were obtained based on the effect of the illumination time on the amount of ROS produced in situ by the encapsulated RB-BSA conjugates. ROS diffusion monitored by ESR was dependent on the molecular weight of copolymer that influences the thickness of the polymer membrane. Upon uptake into HeLa cells our nontoxic nanoreactors acted as a Trojan horse: they produced illumination-controlled ROS in sufficient amounts to induce cell death under photodynamic therapy (PDT) conditions. Straightforward production, stability, and Trojan horse activity inside cells support our light-sensitive nanoreactors for medical applications which require ROS to be generated with precise time and space control.
NASA Astrophysics Data System (ADS)
Savage, J. C.; Simpson, R. W.
2013-09-01
The deformation across the Sierra Nevada Block, the Walker Lane Belt, and the Central Nevada Seismic Belt (CNSB) between 38.5°N and 40.5°N has been analyzed by clustering GPS velocities to identify coherent blocks. Cluster analysis determines the number of clusters required and assigns the GPS stations to the proper clusters. The clusters are shown on a fault map by symbols located at the positions of the GPS stations, each symbol representing the cluster to which the velocity of that GPS station belongs. Fault systems that separate the clusters are readily identified on such a map. Four significant clusters are identified. Those clusters are strips separated by (from west to east) the Mohawk Valley-Genoa fault system, the Pyramid Lake-Wassuk fault system, and the Central Nevada Seismic Belt. The strain rates within the westernmost three clusters approximate simple right-lateral shear (~13 nstrain/a) across vertical planes roughly parallel to the cluster boundaries. Clustering does not recognize the longitudinal segmentation of the Walker Lane Belt into domains dominated by either northwesterly trending, right-lateral faults or northeasterly trending, left-lateral faults.
Favalli, Nicholas; Biendl, Stefan; Hartmann, Marco; Piazzi, Jacopo; Sladojevich, Filippo; Gräslund, Susanne; Brown, Peter J; Näreoja, Katja; Schüler, Herwig; Scheuermann, Jörg; Franzini, Raphael; Neri, Dario
2018-06-01
A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contributed to ligand affinity. Molecules based on a 3,5-bis(aminomethyl)benzoic acid core structure were found to bind human serum albumin with a K d value of 6 nm, while compounds with the same substituents on an equidistant but flexible l-lysine scaffold showed 140-fold lower affinity. A 18 nm tankyrase-1 binder featured l-lysine as linking moiety, while molecules based on d-Lysine or (2S,4S)-amino-l-proline showed no detectable binding to the target. This work suggests that central scaffolds which predispose the orientation of chemical building blocks toward the protein target may enhance the screening productivity of encoded libraries. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Savage, James C.; Simpson, Robert W.
2013-01-01
The deformation across the Sierra Nevada Block, the Walker Lane Belt, and the Central Nevada Seismic Belt (CNSB) between 38.5°N and 40.5°N has been analyzed by clustering GPS velocities to identify coherent blocks. Cluster analysis determines the number of clusters required and assigns the GPS stations to the proper clusters. The clusters are shown on a fault map by symbols located at the positions of the GPS stations, each symbol representing the cluster to which the velocity of that GPS station belongs. Fault systems that separate the clusters are readily identified on such a map. Four significant clusters are identified. Those clusters are strips separated by (from west to east) the Mohawk Valley-Genoa fault system, the Pyramid Lake-Wassuk fault system, and the Central Nevada Seismic Belt. The strain rates within the westernmost three clusters approximate simple right-lateral shear (~13 nstrain/a) across vertical planes roughly parallel to the cluster boundaries. Clustering does not recognize the longitudinal segmentation of the Walker Lane Belt into domains dominated by either northwesterly trending, right-lateral faults or northeasterly trending, left-lateral faults.
NASA Astrophysics Data System (ADS)
Bansal, A. R.; Anand, S.; Rajaram, M.; Rao, V.; Dimri, V. P.
2012-12-01
The depth to the bottom of the magnetic sources (DBMS) may be used as an estimate of the Curie - point depth. The DBMSs can also be interpreted in term of thermal structure of the crust. The thermal structure of the crust is a sensitive parameter and depends on the many properties of crust e.g. modes of deformation, depths of brittle and ductile deformation zones, regional heat flow variations, seismicity, subsidence/uplift patterns and maturity of organic matter in sedimentary basins. The conventional centroid method of DBMS estimation assumes random uniform uncorrelated distribution of sources and to overcome this limitation a modified centroid method based on fractal distribution has been proposed. We applied this modified centroid method to the aeromagnetic data of the central Indian region and selected 29 half overlapping blocks of dimension 200 km x 200 km covering different parts of the central India. Shallower values of the DBMS are found for the western and southern portion of Indian shield. The DBMSs values are found as low as close to middle crust in the south west Deccan trap and probably deeper than Moho in the Chhatisgarh basin. In few places DBMS are close to the Moho depth found from the seismic study and others places shallower than the Moho. The DBMS indicate complex nature of the Indian crust.
Vo, L; Drummond, P D
2013-03-01
In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.
Geophysical Studies of Irish Granites Using Magnetotelluric and Gravity Data
NASA Astrophysics Data System (ADS)
Farrell, T. F.; Muller, M. R.; Rath, V.; Feely, M.; Hogg, C.
2014-12-01
We present results of on-going geophysical studies of Caledonian radiothermal granite bodies in Ireland, which are being undertaken to investigate the volumetric depth extent and structural features of these granites. During three field seasons, magnetotelluric (MT) and audio-magnetotelluric (AMT) data were acquired at 156 sites targeting three separate granite bodies. These studies will contribute to a crustal-scale investigation of the geothermal energy potential of the granites and their contribution to the thermal field of the Irish crust. Across the calc-alkaline Galway granite, located on the Irish west coast, MT and AMT data were acquired at 75 sites distributed in a grid. Preliminary 3D inversion reveals the presence of a resistor, thickest beneath the central block of the granite where it extends to depths of 11 - 12 km. The greater depth of the resistor beneath the central block is in contrast to previous thinking that proposed the central block granites to have shallower depth extent than those of the western block, based on Bouguer anomaly maps of the area in which the western block exhibited a more pronounced negative Bouguer anomaly than the central block. At the S-type Leinster granite, in eastern Ireland and to the south of Dublin, MT and AMT data were acquired along two profiles (LGN - 27 sites and LGS - 32 sites). Preliminary 1D inversions of AMT data along profile LGN show the Northern Units of the Leinster granite to extend to a depth of 4.5 km and the Lugnaquilla pluton extending to 2.5 km depth. MT and AMT data were acquired at 22 sites along a profile across the buried Kentstown granite, 35 km to the NW of Dublin. The Kentstown granite was intersected by two mineral exploration boreholes at depths of 492 m and 663 m. Preliminary 2D inversions do not yet satisfactorily resolve the top of the buried granite. Inversion of MT and AMT data is continuing, with the electrical conductivity structures revealed by these inversions being used to constrain inversions of gravity data. The integration of MT and gravity data will provide an insight into the potential density distribution within the resistors associated with the granites and whether the granites, likely to have elevated heat-production (HP), are underlain by electrically resistive but denser, more mafic bodies, likely to be associated with lower HP.
Rahman, Tanzina; Millwater, Harry; Shipley, Heather J
2014-11-15
Aluminum oxide nanoparticles have been widely used in various consumer products and there are growing concerns regarding their exposure in the environment. This study deals with the modeling, sensitivity analysis and uncertainty quantification of one-dimensional transport of nano-sized (~82 nm) aluminum oxide particles in saturated sand. The transport of aluminum oxide nanoparticles was modeled using a two-kinetic-site model with a blocking function. The modeling was done at different ionic strengths, flow rates, and nanoparticle concentrations. The two sites representing fast and slow attachments along with a blocking term yielded good agreement with the experimental results from the column studies of aluminum oxide nanoparticles. The same model was used to simulate breakthrough curves under different conditions using experimental data and calculated 95% confidence bounds of the generated breakthroughs. The sensitivity analysis results showed that slow attachment was the most sensitive parameter for high influent concentrations (e.g. 150 mg/L Al2O3) and the maximum solid phase retention capacity (related to blocking function) was the most sensitive parameter for low concentrations (e.g. 50 mg/L Al2O3). Copyright © 2014 Elsevier B.V. All rights reserved.
Quirion, François; Meilleur, Luc; Lévesque, Isabelle
2013-07-09
Pluronics are block copolymers composed of a central block of polypropylene oxide and two side chains of polyethylene oxide. They are used in water to generate aggregates and gels or added to phospholipid suspensions to prepare microparticles for drug delivery applications. The structure of these systems has been widely investigated. However, little is known about the mechanisms leading to these structures. This investigation compares the apparent molar volumes and heat capacities of Pluronics F38, F108, F127, P85, P104, and P103 at 25 °C in water and in the presence of lecithin liposomes. The changes in molar volumes, heat capacities, and enthalpies generated by a mass-action model are in good agreement with the loss of hydrophobic hydration of the polypropylene oxide central block of the Pluronics. However, the molecularity of the endothermic transitions is much smaller than the aggregation numbers reported in the literature for the same systems. It is suggested that Pluronics go through dehydration of their central block to form unimolecular or small entities having a hydrophobic polypropylene oxide core. In water, these entities would assemble athermally to form larger aggregates. In the presence of liposomes, they would be transferred into the hydrophobic lecithin bilayers of the liposomes. Light transmission experiments suggest that the liposome suspensions are significantly altered only when the added Pluronics are in the dehydrated state.
Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin
2015-10-01
Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.
The fusimotor and reafferent origin of the sense of force and weight
Luu, Billy L; Day, Brian L; Cole, Jonathan D; Fitzpatrick, Richard C
2011-01-01
Abstract Signals associated with the command the brain sends to muscles are thought to create the sensation of heaviness when we lift an object. Thus, as a muscle is weakened by fatigue or partial paralysis (neuromuscular blockade), the increase in the motor command needed to lift a weight is thought to explain the increasing subjective heaviness of the lifted object. With different fatiguing contractions we approximately halved the force output of the thumb flexor muscles, which were then used to lift an object. For two deafferented subjects the perceived heaviness of the lifted object approximately doubled, in keeping with the central-signal theory. However, for normal subjects this resulted in objects feeling the same or lighter, inconsistent with the central-signal theory but consistent with the expected effects of the conditioning contractions on the sensitivity of peripheral receptors. In separate experiments we subjected the forearm muscles to complete paralysis with a non-depolarising neuromuscular blocking agent and then allowed them to recover to approximately half-force output. This also resulted in objects feeling lighter when lifted by the semi-paralysed thumb, even though the motor command to the motoneurons must have been greater. This is readily explained by reduced lift-related reafference caused by the prolonged paralysis of muscle spindle intrafusal fibres. We conclude that peripheral signals, including a major contribution from muscle spindles, normally give rise to the sense of exerted force. In concept, however, reafference from peripheral receptors may also be considered a centrally generated signal that traverses efferent and then afferent pathways to feed perceptual centres rather than one confined entirely to the central nervous system. These results therefore challenge the distinction between central- and peripheral-based perception, and the concept that muscle spindles provide only information about limb position and movement. PMID:21521756
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ERIC Educational Resources Information Center
Simpkins, N. K.
2014-01-01
This article reports an investigation into undergraduate student experiences and views of a visual or "blocks" based programming language and its environment. An additional and central aspect of this enquiry is to substantiate the perceived degree of transferability of programming skills learnt within the visual environment to a typical…
23. The Stroud Building beard the 'Temme Springs' advertisement. Westfacing ...
23. The Stroud Building beard the 'Temme Springs' advertisement. West-facing windows of the entire block are protected from the afternoon sun by awnings. The north-facing windows of the second-story restaurant were later blocked by an adjacent two-story building. Circa 1914. Credit PPL. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ
Earthquake and volcano clustering via stress transfer at Yucca Mountain, Nevada
Parsons, T.; Thompson, G.A.; Cogbill, A.H.
2006-01-01
The proposed national high-level nuclear waste repository at Yucca Mountain is close to Quaternary cinder cones and faults with Quaternary slip. Volcano eruption and earthquake frequencies are low, with indications of spatial and temporal clustering, making probabilistic assessments difficult. In an effort to identify the most likely intrusion sites, we based a three-dimensional finite-element model on the expectation that faulting and basalt intrusions are sensitive to the magnitude and orientation of the least principal stress in extensional terranes. We found that in the absence of fault slip, variation in overburden pressure caused a stress state that preferentially favored intrusions at Crater Flat. However, when we allowed central Yucca Mountain faults to slip in the model, we found that magmatic clustering was not favored at Crater Flat or in the central Yucca Mountain block. Instead, we calculated that the stress field was most encouraging to intrusions near fault terminations, consistent with the location of the most recent volcanism at Yucca Mountain, the Lathrop Wells cone. We found this linked fault and magmatic system to be mutually reinforcing in the model in that Lathrop Wells feeder dike inflation favored renewed fault slip. ?? 2006 Geological Society of America.
Quantum entanglement and criticality of the antiferromagnetic Heisenberg model in an external field.
Liu, Guang-Hua; Li, Ruo-Yan; Tian, Guang-Shan
2012-06-27
By Lanczos exact diagonalization and the infinite time-evolving block decimation (iTEBD) technique, the two-site entanglement as well as the bipartite entanglement, the ground state energy, the nearest-neighbor correlations, and the magnetization in the antiferromagnetic Heisenberg (AFH) model under an external field are investigated. With increasing external field, the small size system shows some distinct upward magnetization stairsteps, accompanied synchronously with some downward two-site entanglement stairsteps. In the thermodynamic limit, the two-site entanglement, as well as the bipartite entanglement, the ground state energy, the nearest-neighbor correlations, and the magnetization are calculated, and the critical magnetic field h(c) = 2.0 is determined exactly. Our numerical results show that the quantum entanglement is sensitive to the subtle changing of the ground state, and can be used to describe the magnetization and quantum phase transition. Based on the discontinuous behavior of the first-order derivative of the entanglement entropy and fidelity per site, we think that the quantum phase transition in this model should belong to the second-order category. Furthermore, in the magnon existence region (h < 2.0), a logarithmically divergent behavior of block entanglement which can be described by a free bosonic field theory is observed, and the central charge c is determined to be 1.
Russo, Ethan B
2008-04-01
This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
Semiclassical Virasoro blocks from AdS 3 gravity
Hijano, Eliot; Kraus, Per; Perlmutter, Eric; ...
2015-12-14
We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in [1], evaluated in locally AdS 3 geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block — in which two external operators become parametrically heavy — as a certain scattering process involving higher spin gauge fields in AdS 3; thismore » approach highlights the chiral nature of Virasoro blocks. Finally, these techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.« less
BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB
NASA Technical Reports Server (NTRS)
Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)
2003-01-01
The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.
Vollert, Jan; Magerl, Walter; Baron, Ralf; Binder, Andreas; Enax-Krumova, Elena K; Geisslinger, Gerd; Gierthmühlen, Janne; Henrich, Florian; Hüllemann, Philipp; Klein, Thomas; Lötsch, Jörn; Maier, Christoph; Oertel, Bruno; Schuh-Hofer, Sigrid; Tölle, Thomas R; Treede, Rolf-Detlef
2018-06-01
As an indirect approach to relate previously identified sensory phenotypes of patients suffering from peripheral neuropathic pain to underlying mechanisms, we used a published sorting algorithm to estimate the prevalence of denervation, peripheral and central sensitization in 657 healthy subjects undergoing experimental models of nerve block (NB) (compression block and topical lidocaine), primary hyperalgesia (PH) (sunburn and topical capsaicin), or secondary hyperalgesia (intradermal capsaicin and electrical high-frequency stimulation), and in 902 patients suffering from neuropathic pain. Some of the data have been previously published. Randomized split-half analysis verified a good concordance with a priori mechanistic sensory profile assignment in the training (79%, Cohen κ = 0.54, n = 265) and the test set (81%, Cohen κ = 0.56, n = 279). Nerve blocks were characterized by pronounced thermal and mechanical sensory loss, but also mild pinprick hyperalgesia and paradoxical heat sensations. Primary hyperalgesia was characterized by pronounced gain for heat, pressure and pinprick pain, and mild thermal sensory loss. Secondary hyperalgesia was characterized by pronounced pinprick hyperalgesia and mild thermal sensory loss. Topical lidocaine plus topical capsaicin induced a combined phenotype of NB plus PH. Topical menthol was the only model with significant cold hyperalgesia. Sorting of the 902 patients into these mechanistic phenotypes led to a similar distribution as the original heuristic clustering (65% identity, Cohen κ = 0.44), but the denervation phenotype was more frequent than in heuristic clustering. These data suggest that sorting according to human surrogate models may be useful for mechanism-based stratification of neuropathic pain patients for future clinical trials, as encouraged by the European Medicines Agency.
Dutka, T L; Mollica, J P; Lamboley, C R; Weerakkody, V C; Greening, D W; Posterino, G S; Murphy, R M; Lamb, G D
2017-03-01
Nitric oxide is generated in skeletal muscle with activity and decreases Ca 2+ sensitivity of the contractile apparatus, putatively by S- nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca 2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S- glutathionylation of Cys134 on fast troponin I (TnI f ). Force-[Ca 2+ ] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca 2+ -buffered solutions. Treatment with S- nitrosylating agents, S- nitrosoglutathione (GSNO) or S- nitroso- N -acetyl-penicillamine (SNAP), decreased pCa 50 ( = -log 10 [Ca 2+ ] at half-maximal activation) by ~-0.07 pCa units in rat and human FT fibers without affecting maximum force, but had no effect on rat and human slow-twitch fibers or toad or chicken FT fibers, which all lack Cys134. The Ca 2+ sensitivity decrease was 1 ) fully reversed with dithiothreitol or reduced glutathione, 2 ) at least partially reversed with ascorbate, indicative of involvement of S-nitrosylation, and 3 ) irreversibly blocked by low concentration of the alkylating agent, N -ethylmaleimide (NEM). The biotin-switch assay showed that both GSNO and SNAP treatments caused S- nitrosylation of TnI f S- glutathionylation pretreatment blocked the effects of S- nitrosylation on Ca 2+ sensitivity, and vice-versa. S- nitrosylation pretreatment prevented NEM from irreversibly blocking S- glutathionylation of TnI f and its effects on Ca 2+ sensitivity, and likewise S- glutathionylation pretreatment prevented NEM block of S- nitrosylation. Following substitution of TnI f into rat slow-twitch fibers, S- nitrosylation treatment caused decreased Ca 2+ sensitivity. These findings demonstrate that S- nitrosylation and S- glutathionylation exert opposing effects on Ca 2+ sensitivity in mammalian FT muscle fibers, mediated by competitive actions on Cys134 of TnI f . Copyright © 2017 the American Physiological Society.
Stimuli-sensitive polymeric micelles as anticancer drug carriers.
Na, Kun; Sethuraman, Vijay T; Bae, You Han
2006-11-01
Amphiphilic block copolymers often form core-shell type micelles by self-organization of the blocks in an aqueous medium or under specific experimental conditions. Polymeric micelles constructed from these polymers that contain a segment whose physical or chemical properties respond to small changes in environmental conditions are collectively called 'stimuli-sensitive' micelles. This class of nano-scaled constructs has been investigated as a promising anti-cancer drug carrier because the micelles are able to utilize small environmental changes and modify drug release kinetics, biodistribution and the interactions with tissues and cells. This review summarizes the recent progress in stimuli-sensitive micelles for tumor chemotherapy, particularly for those responding to hyperthermic conditions, tumor pH and endosomal/lysosomal pH.
Mahlmeister, J.E.; Peck, W.S.; Haberer, W.V.; Williams, A.C.
1960-03-22
An improved core design for a sodium-cooled, graphitemoderated nuclear reactor is described. The improved reactor core comprises a number of blocks of moderator material, each block being in the shape of a regular prism. A number of channels, extending the length of each block, are disposed around the periphery. When several blocks are placed in contact to form the reactor core, the channels in adjacent blocks correspond with each other to form closed conduits extending the length of the core. Fuel element clusters are disposed in these closed conduits, and liquid coolant is forced through the annulus between the fuel cluster and the inner surface of the conduit. In a preferred embodiment of the invention, the moderator blocks are in the form of hexagonal prisms with longitudinal channels cut into the corners of the hexagon. The main advantage of an "edge-loaded" moderator block is that fewer thermal neutrons are absorbed by the moderator cladding, as compared with a conventional centrally loaded moderator block.
The Positive Inotropic Effect of Pyruvate Involves an Increase in Myofilament Calcium Sensitivity
Torres, Carlos A. A.; Varian, Kenneth D.; Canan, Cynthia H.; Davis, Jonathan P.; Janssen, Paul M. L.
2013-01-01
Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm2, non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure. PMID:23691074
NASA Astrophysics Data System (ADS)
Zhao, Pan; Faure, Michel; Chen, Yan; Shi, Guanzhong; Xu, Bei
2015-09-01
At the northern margin of the North China Block (NCB), the Xilamulun Fault (XMF) is a key belt to decipher the tectonic evolution of Central-Eastern Asia, as it records the Paleozoic final closure of the Paleo-Asian Ocean, and localizes a Late Triassic intracontinental deformation. In this study, structural analysis, 40Ar-39Ar dating, and paleomagnetic studies were performed to investigate the kinematics of the XMF and to further discuss its Triassic geodynamic significance in the Central-Eastern Asia framework after the Paleozoic Central Asian Orogenic evolution. The structural analyses reveal two phases of ductile deformation. The first one (D1), which displays N-verging and E-W trending folds, is related to the Early Paleozoic collisional event between the NCB and the Songliao-Hunshandake Block (SHB). The second phase (D2) displays a high-angle foliation and a pervasive sub-horizontal E-W stretching lineation with kinematic criteria indicative of dextral strike-slip shearing. The 40Ar-39Ar dating on mylonitic granite places the main shearing event around 227-209 Ma. This D2 shearing is coeval with that of the dextral strike-slip Bayan Obo-Chifeng Fault (BCF) and the Chicheng-Fengning-Longhua Fault to the south, which together constitute a dextral shearing fault system on the northern margin of the NCB during the Late Triassic. The paleomagnetic study performed on the Middle Permian Guangxingyuan pluton, located between the XMF and BCF, documents a local clockwise rotation of this pluton with respect to the NCB and SHB. Our multidisciplinary study suggests an NNW-SSE shortening and strike-slip shearing dominated tectonic setting on the northern margin of the NCB during the Late Triassic. Combining the contemporaneous dextral strike-slip movements of the XMF and BCF in northern China and the sinistral strike-slip movement of East Gobi Fault (EGF) in southeastern Mongolia with the large-scale tectonic framework, a Late Triassic NNW-SSE shortening-eastward extrusion tectonic model for Central-Eastern Asia is firstly proposed. The NNW-SSE shortening results in the eastward extrusion of the continental wedge bounded by the BCF and EGF, which is accommodated by the different kinematic patterns of the southern (XMF and BCF) and northwestern (EGF) bounding faults. This shortening-extrusion tectonic framework is tentatively interpreted as the result of the far field forces associated with three Late Triassic lithosphere-scale convergences in East Asia: i) northward intracontinental subduction between the NCB and South China Block, ii) collision of the Qiangtang Block with the Qaidam Block, and iii) southward subduction of the Mongol-Okhotsk Ocean beneath the Mongolia Block.
NASA Astrophysics Data System (ADS)
Zhao, Pan; Faure, Michel; Chen, Yan; Xu, Bei
2017-04-01
At the northern margin of the North China Block (NCB), the Xilamulun Fault (XMF) is a key belt to decipher the tectonic evolution of Central-Eastern Asia, as it records the Paleozoic final closure of the Paleo-Asian Ocean, and localizes a Late Triassic intracontinental deformation. In this study, structural analysis, 40Ar-39Ar dating, and paleomagnetic studies were performed to investigate the kinematics of the XMF and to further discuss its Triassic geodynamic significance in the Central-Eastern Asia framework after the Paleozoic Central Asian Orogenic evolution. The structural analyses reveal two phases of ductile deformation. The first one (D1), which displays N-verging and E-W trending folds, is related to the Early Paleozoic collisional event between the NCB and the Songliao-Hunshandake Block (SHB). The second phase (D2) displays a high-angle foliation and a pervasive sub-horizontalE-W stretching lineation with kinematic criteria indicative of dextral strike-slip shearing. The 40Ar-39Ar dating on mylonitic granite places the main shearing event around 227-209 Ma. This D2 shearing is coeval with that of the dextral strike-slip Bayan Obo-Chifeng Fault (BCF) and the Chicheng-Fengning-Longhua Fault to the south, which together constitute a dextral shearing fault system on the northern margin of the NCB during the Late Triassic. The paleomagnetic study performed on the Middle Permian Guangxingyuan pluton, located between the XMF and BCF, documents a local clockwise rotation of this pluton with respect to the NCB and SHB. Our multidisciplinary study suggests anNNW-SSE shortening and strike-slip shearing dominated tectonic setting on the northern margin of the NCB during the Late Triassic. Combining the contemporaneous dextral strike-slip movements of the XMF and BCF in northern China and the sinistral strike-slip movement of East Gobi Fault (EGF) in southeastern Mongolia with the large-scale tectonic framework, a Late Triassic NNW-SSE shortening-eastward extrusion tectonic model for Central-Eastern Asia is firstly proposed. The NNW-SSE shortening results in the eastward extrusion of the continental wedge bounded by the BCF and EGF, which is accommodated by the different kinematic patterns of the southern (XMF and BCF) and northwestern (EGF) bounding faults. This shortening-extrusion tectonic framework is tentatively interpreted as the result of the far field forces associated with three Late Triassic lithosphere-scale convergences in East Asia: i)northward intracontinental subduction between the NCB and South China Block, ii)collision of the Qiangtang Block with the Qaidam Block, and iii)southward subduction of the Mongol-Okhotsk Ocean beneath the Mongolia Block.
Pharmacological modulation of aversive responsiveness in honey bees
Tedjakumala, Stevanus R.; Aimable, Margaux; Giurfa, Martin
2014-01-01
Within a honey bee colony, individuals performing different tasks exhibit different sensitivities to noxious stimuli. Noxious-stimulus sensitivity can be quantified in harnessed bees by measuring the sting extension response (SER) to a series of increasing voltages. Biogenic amines play a crucial role in the control of insect responsiveness. Whether or not these neurotransmitters affect the central control of aversive responsiveness, and more specifically of electric-shock responsiveness, remains unknown. Here we studied the involvement of the biogenic amines octopamine, dopamine and serotonin, and of the ecdysteroid 20-hydroxyecdisone in the central control of sting responsiveness to electric shocks. We injected pharmacological antagonists of these signaling pathways into the brain of harnessed bees and determined the effect of blocking these different forms of neurotransmission on shock responsiveness. We found that both octopamine and 20-hydroxyecdisone are dispensable for shock responsiveness while dopamine and serotonin act as down-regulators of sting responsiveness. As a consequence, antagonists of these two biogenic amines induce an increase in shock responsiveness to shocks of intermediate voltage; serotonin, can also increase non-specific responsiveness. We suggest that different classes of dopaminergic neurons exist in the bee brain and we define at least two categories: an instructive class mediating aversive labeling of conditioned stimuli in associative learning, and a global gain-control class which down-regulates responsiveness upon perception of noxious stimuli. Serotonergic signaling together with down-regulating dopaminergic signaling may play an essential role in attentional processes by suppressing responses to irrelevant, non-predictive stimuli, thereby allowing efficient behavioral performances. PMID:24431993
Magnetically inferred basement structure in central Saudi Arabia
Johnson, P.R.; Stewart, I.C.F.
1995-01-01
A compilation of magnetic data acquired during the past three decades for a region in central Saudi Arabia where Precambrian basement is partly exposed on the Arabian shield and partly concealed by overlying Phanerozoic strata, shows a central sector of conspicuous N-S-trending anomalies, a heterogeneous western sector of short-wavelength, high-intensity anomalies, and an eastern sector of low- to moderate-intensity broad-wavelength anomalies. Anomalies in the western and central sectors correlate with Neoproterozoic metavolcanic, metasedimentary, and intrusive rocks of the Arabian shield and are interpreted as delineating extensions of shield-type rocks down-dip beneath Phanerozoic cover. These rocks constitute terranes making up part of a Neoproterozoic orogenic belt that underlies Northeast Africa and western Arabia and it is proposed that their magnetically indicated easternmost extent marks the concealed eastern edge of the orogenic belt in central Arabia. The flat magnetic signature of the eastern sector, not entirely accounted for as an effect of deep burial, may reflect the presence of a crustal block different in character to the terranes of the orogenic belt and, speculatively, may outline a continental block that, according to some tectonic models of the region, collided with the Neoproterozoic terranes and thereby caused their deformation and tectonic accretion.
Prabakaran, Mookkan; Ho, Hui-Ting; Prabhu, Nayana; Velumani, Sumathy; Szyporta, Milene; He, Fang; Chan, Kwai-Peng; Chen, Li-Mei; Matsuoka, Yumiko; Donis, Ruben O; Kwang, Jimmy
2009-01-01
Human infections with highly pathogenic H5N1 avian influenza viruses have generally been confirmed by molecular amplification or culture-based methods. Serologic surveillance has potential advantages which have not been realized because rapid and specific serologic tests to detect H5N1 infection are not widely available. Here we describe an epitope-blocking ELISA to detect specific antibodies to H5N1 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (5F8) that binds to an epitope comprising amino acid residues 274-281 (CNTKCQTP) in the HA1 region of H5 hemagglutinin. Database search analysis of publicly available sequences revealed that this epitope is conserved in 100% of the 163 H5N1 viruses isolated from humans. The sensitivity and specificity of the epitope-blocking ELISA for H5N1 were evaluated using chicken antisera to multiple virus clades and other influenza subtypes as well as serum samples from individuals naturally infected with H5N1 or seasonal influenza viruses. The epitope-blocking ELISA results were compared to those of hemagglutinin inhibition (HI) and microneutralization assays. Antibodies to H5N1 were readily detected in immunized animals or convalescent human sera by the epitope-blocking ELISA whereas specimens with antibodies to other influenza subtypes yielded negative results. The assay showed higher sensitivity and specificity as compared to HI and microneutralization. The epitope-blocking ELISA based on a unique 5F8 mAb provided highly sensitive and 100% specific detection of antibodies to H5N1 influenza viruses in human sera.
NASA Astrophysics Data System (ADS)
Jaboyedoff, M.; Derron, M.-H.; Manby, G. M.
2005-01-01
Uplift gradients can provide the location of highly strained zones, which can be considered to be seismic. The Turan block (Central Asia) contains zones with high gradient of uplift velocities, above the threshold 0.04mm km-1year-1. Some of these zones are associated with important seismic activity and others are not correlated with any recent important recorded earthquakes, however, recent faults scarps as well as diverted rivers may indicate a recent tectonic activity. This threshold of gradient is probably a significant rheologic property of the upper crust. On the basis of these considerations the Uzboy river area is proposed as a potential high seismic hazard zone.
Feedback Effects in Computer-Based Skill Learning
1989-09-12
SUPPLEMENTARY NOTATION 17 COSATI CODES 18 SUBJECT TERMS (Continue on reverse if necessary and identify by block number) r FIELD GROUP SUB-GROUP I...rather than tangible feedback ( Barringer & Gholson, 1979) and when they receive punishment (either alone or witih reward) rather than reward alone...34graphed" response latencies across the four conditions ( r = .58), indicating that subjects were sensitive to block-by-block trends in their response
NASA Astrophysics Data System (ADS)
Xia, Qiang-sheng; Ding, Hong-ming; Ma, Yu-qiang
2018-03-01
Efficient delivery of nanoparticles into specific cell interiors is of great importance in biomedicine. Recently, the pH-responsive micelle has emerged as one potential nanocarrier to realize such purpose since there exist obvious pH differences between normal tissues and tumors. Herein, by using dissipative particle dynamics simulation, we investigate the interaction of the pH-sensitive triblock copolymer micelles composed of ligand (L), hydrophobic block (C) and polyelectrolyte block (P) with cell membrane. It is found that the structure rearrangement of the micelle can facilitate its penetration into the lower leaflet of the bilayer. However, when the ligand-receptor specific interaction is weak, the micelles may just fuse with the upper leaflet of the bilayer. Moreover, the ionization degree of polyelectrolyte block and the length of hydrophobic block also play a vital role in the penetration efficiency. Further, when the sequence of the L, P, C beads in the copolymers is changed, the translocation pathways of the micelles may change from direct penetration to Janus engulfment. The present study reveals the relationship between the molecular structure of the copolymer and the uptake of the pH-sensitive micelles, which may give some significant insights into the experimental design of responsive micellar nanocarriers for highly efficient cellular delivery.
Henn, Daniel M; Wright, Roger A E; Woodcock, Jeremiah W; Hu, Bin; Zhao, Bin
2014-03-11
This Article reports on the synthesis of a series of well-defined, tertiary-amine-containing ABA triblock copolymers, composed of a poly(ethylene oxide) (PEO) central block and thermo- and pH-sensitive outer blocks, and the study of the effect of different tertiary amines on thermally induced sol-gel transition temperatures (T(sol-gel)) of their 10 wt % aqueous solutions. The doubly responsive ABA triblock copolymers were prepared from a difunctional PEO macroinitiator by atom transfer radical polymerization of methoxydi(ethylene glycol) methacrylate and ethoxydi(ethylene glycol) methacrylate at a feed molar ratio of 30:70 with ∼5 mol % of either N,N-diethylaminoethyl methacrylate (DEAEMA), N,N-diisopropylaminoethyl methacrylate, or N,N-di(n-butyl)aminoethyl methacrylate. The chain lengths of thermosensitive outer blocks and the molar contents of tertiary amines were very similar for all copolymers. Using rheological measurements, we determined the pH dependences of T(sol-gel) of 10 wt % aqueous solutions of these copolymers in a phosphate buffer. The T(sol-gel) versus pH curves of all polymers exhibited a sigmoidal shape. The T(sol-gel) increased with decreasing pH; the changes were small on both high and low pH sides. At a specific pH, the T(sol-gel) decreased with increasing the hydrophobicity of the tertiary amine, and upon decreasing pH the onset pH value for the T(sol-gel) to begin to increase noticeably was lower for the more hydrophobic tertiary amine-containing copolymer. In addition, we studied the effect of different tertiary amines on the release behavior of FITC-dextran from 10 wt % micellar gels in an acidic medium at 37 and 27 °C. The release profiles for three studied hydrogels at 37 °C were essentially the same, suggesting that the release was dominated by the diffusion of FITC-dextran. At 27 °C, the release was significantly faster for the DEAEMA-containing copolymer, indicating that both diffusion and gel dissolution contributed to the release at this temperature.
Sforna, Luigi; D'Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro; Franciolini, Fabio
2015-01-01
Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs). PMID:25652918
Worden, Timothy A; Mendes, Matthew; Singh, Pratham; Vallis, Lori Ann
2016-10-01
Successful planning and execution of motor strategies while concurrently performing a cognitive task has been previously examined, but unfortunately the varied and numerous cognitive tasks studied has limited our fundamental understanding of how the central nervous system successfully integrates and executes these tasks simultaneously. To gain a better understanding of these mechanisms we used a set of cognitive tasks requiring similar central executive function processes and response outputs but requiring different perceptual mechanisms to perform the motor task. Thirteen healthy young adults (20.6±1.6years old) were instrumented with kinematic markers (60Hz) and completed 5 practice, 10 single-task obstacle walking trials and two 40 trial experimental blocks. Each block contained 20 trials of seated (single-task) trials followed by 20 cognitive and obstacle (30% lower leg length) crossing trials (dual-task). Blocks were randomly presented and included either an auditory Stroop task (AST; central interference only) or a visual Stroop task (VST; combined central and structural interference). Higher accuracy rates and shorter response times were observed for the VST versus AST single-task trials (p<0.05). Conversely, for the obstacle stepping performance, larger dual task costs were observed for the VST as compared to the AST for clearance measures (the VST induced larger clearance values for both the leading and trailing feet), indicating VST tasks caused greater interference for obstacle crossing (p<0.05). These results supported the hypothesis that structural interference has a larger effect on motor performance in a dual-task situation compared to cognitive tasks that pose interference at only the central processing stage. Copyright © 2016 Elsevier B.V. All rights reserved.
Sirohi, Sunil; Schurdak, Jennifer D; Seeley, Randy J; Benoit, Stephen C; Davis, Jon F
2016-07-01
Recent data implicate glucagon-like peptide-1 (GLP-1), a potent anorexigenic peptide released in response to nutrient intake, as a regulator for the reinforcing properties of food, alcohol and psychostimulants. While, both central and peripheral mechanisms mediate effects of GLP-1R signaling on food intake, the extent to which central or peripheral GLP-1R signaling regulates reinforcing properties of drugs of abuse is unknown. Here, we examined amphetamine reinforcement, alcohol intake and hedonic feeding following peripheral administration of EX-4 (a GLP-1 analog) in FLOX and GLP-1R KD(Nestin) (GLP-1R selectively ablated from the central nervous system) mice (n=13/group). First, the effect of EX-4 pretreatment on the expression of amphetamine-induced conditioned place preference (Amp-CPP) was examined in the FLOX and GLP-1R KD(Nestin) mice. Next, alcohol intake (10% v/v) was evaluated in FLOX and GLP-1R KD(Nestin) mice following saline or EX-4 injections. Finally, we assessed the effects of EX-4 pretreatment on hedonic feeding behavior. Results indicate that Amp-CPP was completely blocked in the FLOX mice, but not in the GLP-1R KD(Nestin) mice following EX-4 pretreatment. Ex-4 pretreatment selectively blocked alcohol consumption in the FLOX mice, but was ineffective in altering alcohol intake in the GLP-1R KD(Nestin) mice. Notably, hedonic feeding was partially blocked in the GLP-1R KD(Nestin) mice, whereas it was abolished in the FLOX mice. The present study provides critical insights regarding the nature by which GLP-1 signaling controls reinforced behaviors and underscores the importance of both peripheral and central GLP-1R signaling for the regulation of addictive disorders. Copyright © 2016. Published by Elsevier Inc.
The Lin28/let-7 axis regulates glucose metabolism
Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.
2012-01-01
SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509
NASA Astrophysics Data System (ADS)
Uribe, J.; Aykac, M.; Baghaei, H.; Li, Hongdi; Wang, Yu; Liu, Yaqiang; Wong, V.; Xing, Tao; Ramirez, R.; Wong, Wai-Hoi
2003-06-01
Recent approvals by CMS (HCFA) for reimbursement of positron emission tomography (PET) scans fuels the rapid grow of the PET market, thus creating the need for more affordable dedicated PET scanners. The objective of the work presented here was the development of a BGO position-sensitive block with similar detector area (40 mm /spl times/ 40 mm) and same number of crystals (8 /spl times/ 8) as the block of a commercial BGO PET, using the less expensive photomultiplier quadrant sharing (PQS) technique. This block is coupled to four single-anode 40-mm diameter photomultipliers (PMT) instead of the 19-mm PMT used in a popular commercial BGO PET, and each PMT is shared by four adjacent detector blocks. Potentially, this design needs only 25% of the number of PMT used in the commercial BGO PET. In order not to waste the unused half-row of PMT at the edges of a detector panel/module when the module is made up solely of square blocks, an extended rectangular block has to be developed for the edge-blocks in the module, which maximized the use of the PMT and minimized the gap between modules. Only the extended block needs to be developed to derive the design for all the blocks in the module because the symmetric square block uses the same light-distributing partitions as those along the short side of the extended rectangular block. White-paint masks applied with accurate templates and airbrush were fine-tuned for every pair of adjacent crystals. The experimental block developed in this study provided good crystal-decoding. The composite energy spectrum of all 64 crystals showed a prominent photopeak. The worst crystal sitting in the air space between 4 round PMTs still has 60% of the signal pulse height as the best crystal. The average energy resolution was 21.8% for 511 keV gamma (range 17% - 28.7%) that compared well with the 22% - 44% measured with GE and CTI blocks. The image resolution provided by the PQS blocks is expected to be comparable to that of commercial BGO PETs as similar size crystals were decoded.
Liu, Xiao; Zhu, Ling; Shi, Xiaohong; Xu, Zhiwen; Mei, Miao; Xu, Weiwei; Zhou, Yuancheng; Guo, Wanzhu; Wang, Xiaoyu
2012-12-01
The major epitope region of the glycoprotein B (gB) gene of the porcine cytomegalovirus (PCMV), with a length of 270 bp, was cloned and expressed in Escherichia coli Rosetta (DE3). The major gB epitope was detected using an agar gel precipitation and Western blot analysis with the polyclonal antibodies specific for the major epitope. An indirect-blocking enzyme-linked immunosorbent assay (ELISA) was developed using the expressed major gB epitope as a coating antigen for the detection of PCMV antibodies. The results of the tests show that the indirect-blocking ELISA has 98% specificity and 97.8% sensitivity. No cross-reactions were observed between the major gB epitope and the antibodies against other virus, which indicates that the gB epitope is specific for PCMV antibodies. The indirect-blocking ELISA is a highly specific, sensitive method for detecting anti-PCMV gB antibodies. Copyright © 2012 Elsevier B.V. All rights reserved.
Krýsová, Hana; Krýsa, Josef; Kavan, Ladislav
2018-01-01
For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO 2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO 2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20-200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO 2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO 2 films. The blocking properties of the as-deposited TiO 2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO 2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells.
NASA Astrophysics Data System (ADS)
He, Chuansong; Dong, Shuwen; Chen, Xuanhua; Santosh, M.; Li, Qiusheng
2014-01-01
The Qinling-Tongbai-Hong'an-Dabie-Sulu orogenic belt records the tectonic history of Paleozoic convergence between the South China and North China Blocks. In this study, the distribution of crustal thickness and P- and S-wave velocity ratio (Vp/Vs) is obtained by using the H-k stacking technique from the Dabie-Sulu belt in central China. Our results show marked differences in the crustal structure between the Dabie and Sulu segments of the ultrahigh-pressure (UHP) orogen. The lower crust in the Dabie orogenic belt is dominantly of felsic-intermediate composition, whereas the crust beneath the Sulu segment is largely intermediate-mafic. The crust of the Dabie orogenic belt is thicker by ca. 3-5 km as compared to that of the surrounding region with the presence of an ‘orogenic root’. The crustal thickness is nearly uniform in the Dabie orogenic belt with a generally smooth crust-mantle boundary. A symmetrically thickened crust in the absence of any deep-structural features similar to that of the Yangtze block suggests no supportive evidence for the proposed northward subduction of the Yangtze continental block beneath the North China Block. We propose that the collision between the Yangtze and North China Blocks and extrusion caused crustal shortening and thickening, as well as delamination of the lower crust, resulting in asthenospheric upwelling and lower crustal UHP metamorphism along the Dabie Orogen. Our results also reveal the presence of a SE to NW dipping Moho in the North China Block (beneath the Tran-North China Orogen and Eastern Block), suggesting the fossil architecture of the northwestward subduction of the Kula plate.
Possible mechanisms for four regimes associated with cold events over East Asia
NASA Astrophysics Data System (ADS)
Yang, Zifan; Huang, Wenyu; Wang, Bin; Chen, Ruyan; Wright, Jonathon S.; Ma, Wenqian
2017-09-01
Circulation patterns associated with cold events over East Asia during the winter months of 1948-2014 are classified into four regimes by applying a k-means clustering method based on the area-weighted pattern correlation. The earliest precursor signals for two regimes are anticyclonic anomalies, which evolve into Ural and central Siberian blocking-like circulation patterns. The earliest precursor signals for the other two regimes are cyclonic anomalies, both of which evolve to amplify the East Asian trough (EAT). Both the blocking-like circulation patterns and amplified EAT favor the initialization of cold events. On average, the blocking-related regimes tend to last longer. The lead time of the earliest precursor signal for the central Siberian blocking-related regime is only 4 days, while those for the other regimes range from 16 to 18 days. The North Atlantic Oscillation plays essential roles both in triggering the precursor for the Ural blocking-related regime and in amplifying the precursors for all regimes. All regimes preferentially occur during the positive phase of the Eurasian teleconnection pattern and the negative phase of the El Niño-Southern Oscillation. For three regimes, surface cooling is primarily due to reduced downward infrared radiation and enhanced cold advection. For the remaining regime, which is associated with the southernmost cooling center, sensible and latent heat release and horizontal cold advection dominate the East Asian cooling.
Hettinger, Thomas P.; Savoy, Lawrence D.; Frank, Marion E.
2012-01-01
Component signaling in taste mixtures containing both beneficial and dangerous chemicals depends on peripheral processing. Unidirectional mixture suppression of chorda tympani (CT) nerve responses to sucrose by quinine and acid is documented for golden hamsters (Mesocricetus auratus). To investigate mixtures of NaCl and acids, we recorded multifiber responses to 50 mM NaCl, 1 and 3 mM citric acid and acetic acid, 250 μM citric acid, 20 mM acetic acid, and all binary combinations of each acid with NaCl (with and without 30 μM amiloride added). By blocking epithelial Na+ channels, amiloride treatment separated amiloride-sensitive NaCl-specific responses from amiloride-insensitive electrolyte-generalist responses, which encompass all of the CT response to the acids as well as responses to NaCl. Like CT sucrose responses, the amiloride-sensitive NaCl responses were suppressed by as much as 50% by citric acid (P = 0.001). The amiloride-insensitive electrolyte-generalist responses to NaCl + acid mixtures approximated the sum of NaCl and acid component responses. Thus, although NaCl-specific responses to NaCl were weakened in NaCl–acid mixtures, electrolyte-generalist responses to acid and NaCl, which tastes KCl-like, were transmitted undiminished in intensity to the central nervous system. The 2 distinct CT pathways are consistent with known rodent behavioral discriminations. PMID:22451526
Lima, Michelle; Bouzid, Hana; Soares, Daniele G; Selle, Frédéric; Morel, Claire; Galmarini, Carlos M; Henriques, João A P; Larsen, Annette K; Escargueil, Alexandre E
2016-05-03
Trabectedin (Yondelis®, ecteinascidin-743, ET-743) is a marine-derived natural product approved for treatment of advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent structurally related to trabectedin. Both ecteinascidins generate DNA double-strand breaks that are processed through homologous recombination repair (HRR), thereby rendering HRR-deficient cells particularly sensitive. We here characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia-telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3-related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM is an absolute requirement to efficiently block the formation of γ-H2AX, MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These results are not restricted to HeLa cells, but are shared by cisplatin-sensitive and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors.
75 FR 18231 - Central Utah Project Completion Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-09
... a proposed conversion of up to 12,100 acre feet of Central Utah Project (CUP) Bonneville Unit water... that has been made available under Block Notice 1A of the CUP. The delivery area could be expanded to include additional land in Wasatch County. The Bonneville Unit of the CUP was authorized to develop a...
Nakato, Yasuya; Abekawa, Tomohiro; Inoue, Takeshi; Ito, Koki; Koyama, Tsukasa
2011-10-24
We recently proposed a new psychostimulant animal model of the progressive pathophysiological changes of schizophrenia. Studies using that model produced a treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated high-dosage methamphetamine (METH)-induced initiation and expression of prepulse inhibition deficit and development of apoptosis in the medial prefrontal cortex (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior induced by METH or NMDA receptor antagonists is regarded as an animal model of schizophrenia. This study examined the effects of LTG on the development of behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801) by repeated administration of high-dose METH (2.5mg/kg, 10 times s.c.). Rats were injected repeatedly with LTG (30mg/kg) after 120min METH administration (2.5mg/kg). Repeated co-administration of LTG blocked the development of behavioral cross-sensitization to MK-801 (0.15mg/kg), but it did not prevent behavioral sensitization to METH (0.2mg/kg). The LTG-induced prevention of increased glutamate by high-dose METH might be related to the former finding. Combined results of our previous studies and this study suggest that LTG is useful to treat schizophrenia, especially at a critical point in its progression. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Witten diagrams revisited: the AdS geometry of conformal blocks
Hijano, Eliot; Kraus, Per; Perlmutter, Eric; ...
2016-01-25
Here, we develop a new method for decomposing blocks. The steps involved are elementary, requiring no explicit integration, and operate directly in position space. Central to this construction is an appealingly simple answer to the question: what object in AdS computes a conformal block? The answer is a "geodesic Witten diagram", which is essentially an ordinary exchange Witten diagram, except that the cubic vertices are not integrated over all of AdS, but only over bulk geodesics connecting the boundary operators. In particular, we also consider the case of four-point functions of scalar operators, and show how to easily reproduce existingmore » results for the relevant conformal blocks in arbitrary dimension.« less
Plate kinematics of the Afro-Arabian Rift System with emphasis on the Afar Depression, Ethiopia
NASA Astrophysics Data System (ADS)
Bottenberg, Helen Carrie
This work utilizes the Four-Dimensional Plates (4DPlates) software, and Differential Interferometric Synthetic Aperture Radar (DInSAR) to examine plate-scale, regional-scale and local-scale kinematics of the Afro-Arabian Rift System with emphasis on the Afar Depression in Ethiopia. First, the 4DPlates is used to restore the Red Sea, the Gulf of Aden, the Afar Depression and the Main Ethiopian Rift to development of a new model that adopts two poles of rotation for Arabia. Second, the 4DPlates is used to model regional-scale and local-scale kinematics within the Afar Depression. Most plate reconstruction models of the Afro-Arabian Rift System relies on considering the Afar Depression as a typical rift-rift-rift triple junction where the Arabian, Somali and Nubian (African) plates are separating by the Red Sea, the Gulf of Aden and the Main Ethiopian Rift suggesting the presence of "sharp and rigid" plate boundaries. However, at the regional-scale the Afar kinematics are more complex due to stepping of the Red Sea propagator and the Gulf of Aden propagator onto Afar as well as the presence of the Danakil, Ali Sabieh and East Central Block "micro-plates". This study incorporates the motion of these micro-plates into the regional-scale model and defined the plate boundary between the Arabian and the African plates within Afar as likely a diffused zone of extensional strain within the East Central Block. Third, DInSAR technology is used to create ascending and descending differential interferograms from the Envisat Advanced Synthetic Aperture Radar (ASAR) C-Band data for the East Central Block to image active crustal deformation related to extensional tectonics and volcanism. Results of the DInSAR study indicate no strong strain localization but rather a diffused pattern of deformation across the entire East Central Block.
Mason, Bianca N; Kaiser, Eric A; Kuburas, Adisa; Loomis, Maria-Cristina M; Latham, John A; Garcia-Martinez, Leon F; Russo, Andrew F
2017-01-04
The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT 1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms. Copyright © 2017 the authors 0270-6474/17/370204-13$15.00/0.
Nanoparticle optical notch filters
NASA Astrophysics Data System (ADS)
Kasinadhuni, Pradeep Kumar
Developing novel light blocking products involves the design of a nanoparticle optical notch filter, working on the principle of localized surface plasmon resonance (LSPR). These light blocking products can be used in many applications. One such application is to naturally reduce migraine headaches and light sensitivity. Melanopsin ganglion cells present in the retina of the human eye, connect to the suprachiasmatic nucleus (SCN-the body's clock) in the brain, where they participate in the entrainment of the circadian rhythms. As the Melanopsin ganglion cells are involved in triggering the migraine headaches in photophobic patients, it is necessary to block the part of visible spectrum that activates these cells. It is observed from the action potential spectrum of the ganglion cells that they absorb light ranging from 450-500nm (blue-green part) of the visible spectrum with a λmax (peak sensitivity) of around 480nm (blue line). Currently prescribed for migraine patients is the FL-41 coating, which blocks a broad range of wavelengths, including wavelengths associated with melanopsin absorption. The nanoparticle optical notch filter is designed to block light only at 480nm, hence offering an effective prescription for the treatment of migraine headaches.
van Helmond, Noud; Steegers, Monique A.; Filippini-de Moor, Gertie P.; Vissers, Kris C.; Wilder-Smith, Oliver H.
2016-01-01
Background Persistent pain is a challenging clinical problem after breast cancer treatment. After surgery, inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain. Using quantitative sensory testing, we tested the hypothesis that adding COX-2 inhibition to standard treatment reduces hyperalgesia after breast cancer surgery. A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia. Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were randomized to COX-2 inhibition (2x40mg parecoxib on day of surgery, thereafter 2x200mg celecoxib/day until day five) or placebo. Preoperatively and 1, 5, 15 days and 1, 3, 6, 12 months postoperatively, we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100mm VAS score for pain. We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication. To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months. Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis. Contrary to our primary hypothesis, change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo. COX-2 inhibition had an effect on pain on movement at postoperative day 5 (p<0.01). Consistent with our secondary hypothesis, change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain (p<0.01) from day 5 to 1 year postoperatively. Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery. Central sensitization may play a role in the genesis of persistent postsurgical pain. PMID:27935990
Neural and psychosocial mechanisms of pain sensitivity in fibromyalgia.
English, Brian
2014-06-01
Fibromyalgia is a chronic musculoskeletal pain disorder that affects an estimated 5 million adults in the U.S. The hallmark is burning, searing, tingling, shooting, stabbing, deep aching, or sharp pain. Fibromyalgia is generally considered to be a "central sensitivity syndrome" where central sensitization is regarded as the cause of pain in its own right. Nonetheless, the case continues to be made that all central and spatially distributed peripheral components of fibromyalgia pain would fade if the peripheral generators could be silenced. Although neural mechanisms are clearly important in pain sensitivity, cognitive and social mechanisms also need to be considered. The aim of this review is to examine four mechanisms responsible for heightened pain sensitivity in fibromyalgia: peripheral sensitization, central sensitization, cognitive-emotional sensitization, and interpersonal sensitization. The purpose of framing the review in terms of pain sensitivity in fibromyalgia is to highlight that different mechanisms of sensitization are appropriately regarded as intervening variables when it comes to understanding individual differences in the experience of pain. The paper concludes by considering the implications of the findings of the review for explanations of fibromyalgia pain by nurses working in multidisciplinary teams. The trend appears to be able to explain the cause of fibromyalgia pain in terms of sensitization per se. The recommended alternative is to explain fibromyalgia pain in terms of changes in pain sensitivity and the role of underlying neural and psychosocial mechanisms. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
Sphenopalatine ganglion: block, radiofrequency ablation and neurostimulation - a systematic review.
Ho, Kwo Wei David; Przkora, Rene; Kumar, Sanjeev
2017-12-28
Sphenopalatine ganglion is the largest collection of neurons in the calvarium outside of the brain. Over the past century, it has been a target for interventional treatment of head and facial pain due to its ease of access. Block, radiofrequency ablation, and neurostimulation have all been applied to treat a myriad of painful syndromes. Despite the routine use of these interventions, the literature supporting their use has not been systematically summarized. This systematic review aims to collect and summarize the level of evidence supporting the use of sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were reviewed for studies on sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Studies included in this review were compiled and analyzed for their treated medical conditions, study design, outcomes and procedural details. Studies were graded using Oxford Center for Evidence-Based Medicine for level of evidence. Based on the level of evidence, grades of recommendations are provided for each intervention and its associated medical conditions. Eighty-three publications were included in this review, of which 60 were studies on sphenopalatine ganglion block, 15 were on radiofrequency ablation, and 8 were on neurostimulation. Of all the studies, 23 have evidence level above case series. Of the 23 studies, 19 were on sphenopalatine ganglion block, 1 study on radiofrequency ablation, and 3 studies on neurostimulation. The rest of the available literature was case reports and case series. The strongest evidence lies in using sphenopalatine ganglion block, radiofrequency ablation and neurostimulation for cluster headache. Sphenopalatine ganglion block also has evidence in treating trigeminal neuralgia, migraines, reducing the needs of analgesics after endoscopic sinus surgery and reducing pain associated with nasal packing removal after nasal operations. Overall, sphenopalatine ganglion is a promising target for treating cluster headache using blocks, radiofrequency ablation and neurostimulation. Sphenopalatine ganglion block also has some evidence supporting its use in a few other conditions. However, most of the controlled studies were small and without replications. Further controlled studies are warranted to replicate and expand on these previous findings.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-24
... Western Gulf of Mexico Planning Areas, Oil and Gas Lease Sales for Years 2012-2017 (Sales 229, 227, 233... Register (76 FR 70748) correcting the sale numbers that were identified in the Call. This document... them with: 1. Whole blocks and portions of blocks deferred by the Gulf of Mexico Energy Security Act of...
NASA Astrophysics Data System (ADS)
Samuel, Vinod O.; Sajeev, K.; Hokada, T.; Horie, K.; Itaya, T.
2015-11-01
The Nilgiri Block, southern India is an exhumed lower crust formed through arc magmatic processes in the Neoarchean. The main lithologies in this terrane include charnockites, gneisses, volcanic tuff, metasediments, banded iron formation and mafic-ultramafic bodies. Mafic-ultramafic rocks are present towards the northern and central part of the Nilgiri Block. We examine the evolution of these mafic granulites/metagabbros by phase diagram modeling and U-Pb sensitive high resolution ion microprobe (SHRIMP) dating. They consist of a garnet-clinopyroxene-plagioclase-hornblende-ilmenite ± orthopyroxene ± rutile assemblage. Garnet and clinopyroxene form major constituents with labradorite and orthopyroxene as the main mineral inclusions. Labradorite, identified using Raman analysis, shows typical peaks at 508 cm- 1, 479 cm- 1, 287 cm- 1 and 177 cm- 1. It is stable along with orthopyroxene towards the low-pressure high-temperature region of the granulite facies (M1 stage). Subsequently, orthopyroxene reacted with plagioclase to form the peak garnet + clinopyroxene + rutile assemblage (M2 stage). The final stage is represented by amphibolite facies-hornblende and plagioclase-rim around the garnet-clinopyroxene assemblage (M3 stage). Phase diagram modeling shows that these mafic granulites followed an anticlockwise P-T-t path during their evolution. The initial high-temperature metamorphism (M1 stage) was at 850-900 °C and ~ 9 kbar followed by high-pressure granulite facies metamorphism (M2 stage) at 850-900 °C and 14-15 kbar. U-Pb isotope studies of zircons using SHRIMP revealed late Neoarchean to early paleoproterozoic ages of crystallization and metamorphism respectively. The age data shows that these mafic granulites have undergone arc magmatism at ca. 2539.2 ± 3 Ma and high-temperature, high-pressure metamorphism at ca. 2458.9 ± 8.6 Ma. Thus our results suggests a late Neoarchean arc magmatism followed by early paleoproterozoic high-temperature, high-pressure granulite facies metamorphism due to the crustal thickening and suturing of the Nilgiri Block onto the Dharwar Craton.
Möhwald, Ken; Bardins, Stanislavs; Müller, Hans-Helge; Jahn, Klaus; Zwergal, Andreas
2017-10-10
Identifying stroke as a cause of acute vertigo, dizziness and imbalance in the emergency room is still a clinical challenge. Many patients are admitted to stroke units, but only a minority will have strokes. This imposes a heavy financial burden on the healthcare system. The aim of this study is to develop a diagnostic index test to identify patients with a high risk of having a stroke as the cause of acute vertigo and imbalance. Patients with acute onset of vertigo, dizziness, postural imbalance or double vision within the last 24 hours lasting for at least 10 min are eligible to be included in the study. Patients with clinically proven peripheral or central aetiology will be excluded. In the emergency room, all enrolled patients will undergo standardised neuro-ophthalmological/physiological testing (including video-oculography, mobile posturography, measurement of subjective visual vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2 will be compared with results from block 1 in order to devise a diagnostic index test with a high specificity and sensitivity to predict the risk of stroke in the emergency room. The study was approved by the ethics committee of the University of Munich and will be conducted according to the Guideline for Good Clinical Practice, the Federal Data Protecting Act and the Helsinki Declaration of the World Medical Association in its recent version. Study results are expected to be published in international peer-reviewed journals and will be presented at international conferences. German Clinical Trial Register: DRKS00008992; Universal trial number: U1111-1172-8719); pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Bardins, Stanislavs; Müller, Hans-Helge; Jahn, Klaus; Zwergal, Andreas
2017-01-01
Introduction Identifying stroke as a cause of acute vertigo, dizziness and imbalance in the emergency room is still a clinical challenge. Many patients are admitted to stroke units, but only a minority will have strokes. This imposes a heavy financial burden on the healthcare system. The aim of this study is to develop a diagnostic index test to identify patients with a high risk of having a stroke as the cause of acute vertigo and imbalance. Methods and analysis Patients with acute onset of vertigo, dizziness, postural imbalance or double vision within the last 24 hours lasting for at least 10 min are eligible to be included in the study. Patients with clinically proven peripheral or central aetiology will be excluded. In the emergency room, all enrolled patients will undergo standardised neuro-ophthalmological/physiological testing (including video-oculography, mobile posturography, measurement of subjective visual vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2 will be compared with results from block 1 in order to devise a diagnostic index test with a high specificity and sensitivity to predict the risk of stroke in the emergency room. Ethics and dissemination The study was approved by the ethics committee of the University of Munich and will be conducted according to the Guideline for Good Clinical Practice, the Federal Data Protecting Act and the Helsinki Declaration of the World Medical Association in its recent version. Study results are expected to be published in international peer-reviewed journals and will be presented at international conferences. Trial registration number German Clinical Trial Register: DRKS00008992; Universal trial number: U1111-1172-8719); pre-results. PMID:29018076
NASA Astrophysics Data System (ADS)
Yu, Yang; Huang, Xiao-Long; Sun, Min; He, Peng-Li
2018-05-01
The early Paleozoic Wuyi-Yunkai orogen was associated with extensive felsic magmatic activities and the orogenic core was mainly distributed in the Yunkai and Wugong domains located in the western Cathaysia block and in the Wuyi domain located in the central part of the Cathaysia block. In order to investigate the evolution of the Wuyi-Yunkai orogen, elemental and Sr-Nd isotopic analyses were performed for granites from the Baoxu pluton in the Yunkai domain and from the Enping pluton in the central part of the Cathaysia block. The Baoxu pluton consists of biotite granite with abundant xenoliths of gneissic granite, granodiorite and diorite, and the Enping pluton is mainly composed of massive granodiorite. Biotite granites (441 ± 5 Ma) and gneissic granite xenolith (443 ± 4 Ma) of the Baoxu pluton are all weakly peraluminous (A/CNK = 1.05-1.10). They show high Sr/Y and La/Yb ratios and have negative bulk-rock εNd(t) values (-7.0 to -4.4), which are similar to coeval gneissic S-type granites in the Yunkai domain and were probably derived from dehydration melting of a sedimentary source with garnet residue in the source. Granodiorites (429 ± 3 Ma) from Enping and granodiorite xenolith (442 ± 4 Ma) from Baoxu are metaluminous and have REE patterns with enriched light REE and flat middle to heavy REE, possibly generated by the dehydration melting of an igneous basement at middle to lower crustal level. Diorite xenolith from Baoxu is ultrapotassic (K2O = 4.9 wt%), has high contents of MgO (7.0 wt%), Cr (379 ppm) and Ni (171 ppm) and shows pronounced negative Nb, Ta and Ti anomalies. This xenolith also has negative εNd(t) value (-3.6) and low Rb/Ba and high Ba/Sr ratios, and is thus interpreted to be derived from an enriched lithospheric mantle with the breakdown of phlogopite. Early Paleozoic I- and S-type granites in the Wuyi-Yunkai orogen mostly have negative εNd(t) values and do not have juvenile components, consistent with genesis by an intracontinental orogenic event. These early Paleozoic granites occur near the ancient suture zone between the Yangtze and Cathaysia blocks and have high La/Yb and Sr/Y ratios, likely due to the existence of residual garnet in the source, suggesting the thickened crust at ca. 440 Ma. The 450-440 Ma gneissic S-type granites near the suture zone are earlier than those in the central part of the Cathaysia block (∼430 Ma). The crustal thickening along the ancient suture zone at 440 Ma propagated into the central part of the Cathaysia block as evidenced by the 430 Ma granites. Early Paleozoic I-type granites near the suture zone clearly show involvement of significant mantle-derived materials, in contrast to granites in the central part of the Cathaysia block. The ancient suture zone may have acted as channels for the emplacement of mafic magmas during the collapse of an intracontinental orogen.
Strong signatures of high-latitude blocks and subtropical ridges in winter PM10 over Europe
NASA Astrophysics Data System (ADS)
Garrido-Perez, Jose M.; Ordóñez, Carlos; García-Herrera, Ricardo
2017-10-01
This paper analyses the impact of high-latitude blocks and subtropical ridges on daily PM10 (particulate matter ≤ 10 μm) observations obtained from the European Environment Agency's air quality database (AirBase) for the winter period of 2000-2010. The response of the pollutant concentrations to the location of blocks and ridges with centres in two main longitudinal sectors (Atlantic, ATL, 30°-0° W; European, EUR, 0°-30° E) is examined. In particular, EUR blocking is associated with a collapse of the boundary layer as well as reduced wind speeds and precipitation occurrence, yielding large positive anomalies which average 12 μg m-3 over the whole continent. Conversely, the enhanced zonal flow around 50°-60° N and the increased occurrence of precipitation over northern-central Europe on days with ATL ridges favour the ventilation of the boundary layer and the impact of washout processes, reducing PM10 concentrations on average by around 8 μg m-3. The presence of EUR blocks is also concurrent with an increased probability of exceeding the air quality target (50 μg m-3 for 24-h averaged PM10) and the local 90th percentiles for this pollutant at many sites in central Europe, while the opposite effect is found for ridges. In addition, the effect of synoptic persistence on the PM10 concentrations is stronger for EUR blocks than for ATL ridges. This could benefit the predictability of PM10 extremes over wide areas of the region. Finally, we have found that the combined or isolated effect of both synoptic patterns can partly control the interannual variability of winter mean PM10 at many sites of north-western and central Europe, with coefficients of determination (R2) exceeding 0.80 for southern Germany. These results indicate that the response of the particulate matter (PM) concentrations to large-scale circulation patterns is stronger than previously reported for Europe and other mid-latitude regions.
Universal Strategy To Reduce Noise Current for Sensitive Organic Photodetectors.
Xiong, Sixing; Li, Lingliang; Qin, Fei; Mao, Lin; Luo, Bangwu; Jiang, Youyu; Li, Zaifang; Huang, Jinsong; Zhou, Yinhua
2017-03-15
Low noise current is critical for achieving high-detectivity organic photodetectors. Inserting charge-blocking layers is an effective approach to suppress the reverse-biased dark current. However, in solution-processed organic photodetectors, the charge-transport material needs to be dissolved in solvents that do not dissolve the underneath light-absorbing layer, which is not always possible for all kinds of light-absorbing materials developed. Here, we introduce a universal strategy of transfer-printing a conjugated polymer, poly(3-hexylthiophene) (P3HT), as the electron-blocking layer to realize highly sensitive photodetectors. The transfer-printed P3HT layers substantially and universally reduced the reverse-biased dark current by about 3 orders of magnitude for various photodetectors with different active layers. These photodetectors can detect the light signal as weak as several picowatts per square centimeter, and the device detectivity is over 10 12 Jones. The results suggest that the strategy of transfer-printing P3HT films as the electron-blocking layer is universal and effective for the fabrication of sensitive organic photodetectors.
Assessment of Central Visual Function in Patients with Retinitis Pigmentosa.
Fujiwara, Kohta; Ikeda, Yasuhiro; Murakami, Yusuke; Tachibana, Takashi; Funatsu, Jun; Koyanagi, Yoshito; Nakatake, Shunji; Yoshida, Noriko; Nakao, Shintaro; Hisatomi, Toshio; Yoshida, Shigeo; Yoshitomi, Takeshi; Ishibashi, Tatsuro; Sonoda, Koh-Hei
2018-05-23
In order to clarify the disease progression in retinitis pigmentosa (RP) and its related factors, reliable data on the changes in central visual function in RP are needed. In this longitudinal study, we examined 118 patients who were diagnosed with typical RP. Visual acuity (VA), visual field using a Humphrey Field Analyzer with the central 10-2 SITA-Standard program, and optical coherence tomography measurements were obtained. The slopes, which were derived from serial values of mean deviation (MD), macular sensitivity (MS), or foveal sensitivity (FS) obtained for each eye by a linear mixed model, were used for analysis. MS and FS were calculated as the average retinal sensitivity of 12 and 4 central points respectively. There were statistically significant interactions of times with levels of the central subfield thickness (CST) on the slopes of MS and FS. Compared to the eyes without macular complications, the eyes with macular complications had steeper MD, MS and FS slopes, and this interaction was no significant, but marginal trend for the MS or FS slope (P = 0.10, 0.05, respectively). The central retinal sensitivity (i.e., MS and FS) slopes calculated were effective indices of the progression of central visual function in RP.
Proterozoic metamorphism and uplift history of the north-central Laramie Mountains, Wyoming, USA
Patel, S.C.; Frost, B.R.; Chamberlain, K.R.; Snyder, G.L.
1999-01-01
The Laramie Mountains of south-eastern Wyoming contain two metamorphic domains that are separated by the 1.76 Ga. Laramie Peak shear zone (LPSZ). South of the LPSZ lies the Palmer Canyon block, where apatite U-Pb ages are c. 1745 Ma and the rocks have undergone Proterozoic kyanite-grade Barrovian metamorphism. In contrast, in the Laramie Peak block, north of the shear zone, the U-Pb apatite ages are 2.4-2.1 Ga, the granitic rocks are unmetamorphosed and supracrustal rocks record only low-T amphibolite facies metamorphism that is Archean in age. Peak mineral assemblages in the Palmer Canyon block include (a) quartz-biotite-plagioclase-garnet-staurolite-kyanite in the pelitic schists; (b) quartz-biotite-plagioclase-low-Ca amphiboles-kyanite in Mg-Al-rich schists, and locally (c) hornblende-plagioclase-garnet in amphibolites. All rock types show abundant textural evidence of decompression and retrograde re-equilibration. Notable among the texturally late minerals are cordierite and sapphirine, which occur in coronas around kyanite in Mg-Al-rich schists. Thermobarometry from texturally early and late assemblages for samples from different areas within the Palmer Canyon block define decompression from > 7 kbar to < 3 kbar. The high-pressure regional metamorphism is interpreted to be a response to thrusting associated with the Medicine Bow orogeny at c. 1.78-1.76 Ga. At this time, the north-central Laramie Range was tectonically thickened by as much as 12 km. This crustal thickening extended for more than 60 km north of the Cheyenne belt in southern Wyoming. Late in the orogenic cycle, rocks of the Palmer Canyon block were uplifted and unroofed as the result of transpression along the Laramie Peak shear zone to produce the widespread decompression textures. The Proterozoic tectonic history of the central Laramie Range is similar to exhumation that accompanied late-orogenic oblique convergence in many Phanerozoic orogenic belts.
NASA Astrophysics Data System (ADS)
Ronkin, Yu. L.; Shardakova, G. Yu.; Maslov, A. V.; Shagalov, E. S.; Lepikhina, O. P.
2009-04-01
Petrogeochemical and isotopic-geochronological signatures in granitoids developed in structures with complex geological history represent an important feature for reconstructing paleogeodynamic settings. Granitoids are widespread in the western slope of the Urals, where the Uralian Orogen contacts via a collage of different-age blocks of the east European Platform. The Ufalei block located in the Central Urals megazone at the junction between the South and Middle Urals’ segments represents one such boundary structure with multistage geological evolution. The isotopic ages obtained by different methods for acid igneous rocks range from 1290 to 245 Ma. We determined close Rb-Sr and Sm-Nd ages (317 Ma) for granites of the Nizhnii Ufalei Massif. By their petrochemical parameters, granitoids and host granite-gneisses differ principally from each other: the former are close to subduction-related, while the latter, to continental-riftogenic varieties. The primary ratio (87Sr/86Sr)0 = 0.70428 and ɛNd ≈ +4 values indicate significant contribution of oceanic (island-arc?) material to the substrate, which served as a source for granites of the Nizhnii Ufalei Massif. Model Nd ages of granites vary from 641 to 550 Ma. Distinct oceanic rocks and varieties with such ages are missing from the surrounding structures. New isotopic dates obtained for ultramafic and mafic rocks from different zones of the Urals related to the Cadomian cycle imply development of unexposed Upper Riphean-Vendian “oceanic” rocks in the central part of the Ufalei block, which played a substantial role in the formation of the Nizhnii Ufalei granitoids. Such rocks could be represented, for example, by fragments of the Precambrian Timanide-type ophiolite association. The analysis of original materials combined with published data point to the heterogeneous composition and structure of the Ufalei block and a significant part of the western segment of the Central Uralian Uplift and extremely complex geological history of the region coupling the Uralian Orogen with the East European Platform in the present-day structure.
NASA Astrophysics Data System (ADS)
La Femina, P. C.; Geirsson, H.; Kobayashi, D.
2012-12-01
Cocos - Caribbean convergence along the Middle America Trench, including subduction of the Cocos Ridge and seamount domain, and Nazca - Caribbean oblique convergence along the South Panama Deformed Belt have resulted in complex plate boundary zone deformation since Miocene - Pliocene time. Plate boundary evolution and upper plate deformation in the western Caribbean is well studied and indicates, 1) Quaternary migration of the volcanic arc toward the back-arc northwest of the Cocos Ridge; 2) Pleistocene to present northwestward motion of the Central American Fore Arc (CAFA); 3) Quaternary to present deformation within the Central Costa Rica Deformed Belt; 4) Miocene-Pliocene cessation of volcanism and uplift of the Cordillera de Talamanca inboard the ridge; 5) Quaternary to present shortening across the fore-arc Fila Costeña fold and thrust belt and back-arc North Panama Deformed Belt (NPDB); 6) Quaternary to present outer fore-arc uplift above the seamount domain (Nicoya Peninsula), and above (Osa Peninsula) and flanking (Burica Peninsula) the ridge; and 7) Quaternary to present faulting along the Sona-Azuero and Canal Discontinuity fault systems. We investigate the dynamic effects of Cocos and Nazca convergence along the entire Central American margin, and the implications on western Caribbean plate boundary evolution with a new GPS derived three-dimensional (horizontal and vertical) velocity field and kinematic block and geodynamic models. Specifically, we test the hypotheses that the Cocos Ridge is the main driver for upper plate deformation and that there is an independent Panama block. Our model results provide new Euler vectors for the CAFA and Panama block, rates of relative plate and block motions in the region, and constraints on interseismic coupling along the Middle America Trench and other major block bounding fault systems. These results are compared to existing geophysical and geologic data for the region and add insights into the rates of deformation across the regions listed above. We demonstrate that Cocos Ridge collision drives northwest-directed motion of the CAFA and the northeast-directed motion of the Panama region. The Panama region is driven into the Caribbean across the NPDB and into the Choco and North Andes blocks of northwestern South America, which are also converging with the Panama region, pushing it toward the west-northwest. Motion of the Panama region can be fit by an Euler vector suggesting that it is a rigid block, however, this is not in agreement with Quaternary faulting across the isthmus.
Hu, Jinming; Li, Changhua; Liu, Shiyong
2010-01-19
We report on novel type of responsive double hydrophilic block copolymer (DHBC)-based multifunctional chemosensors to Hg(2+) ions, pH, and temperatures and investigate the effects of thermo-induced micellization on the detection sensitivity. Well-defined DHBCs bearing rhodamine B-based Hg(2+)-reactive moieties (RhBHA) in the thermo-responsive block, poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-RhBHA) (PEO-b-P(NIPAM-co-RhBHA)), were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Nonfluorescent RhBHA moieties are subjected to selective ring-opening reaction upon addition of Hg(2+) ions or lowering solution pH, producing highly fluorescent acyclic species. Thus, at room temperature PEO-b-P(NIPAM-co-RhBHA) DHBCs can serve as water-soluble multifunctional and efficient fluorescent chemosensors to Hg(2+) ions and pH. Upon heating above the lower critical solution temperature (approximately 36 degrees C) of the PNIPAM block, they self-assemble into micelles possessing P(NIPAM-co-RhBHA) cores and well-solvated PEO coronas, which were fully characterized by dynamic and static laser light scattering. It was found that the detection sensitivity to Hg(2+) ions and pH could be dramatically improved at elevated temperatures due to fluorescence enhancement of RhBHA residues in the acyclic form, which were embedded within hydrophobic cores of thermo-induced micellar aggregates. This work represents a proof-of-concept example of responsive DHBC-based multifunctional fluorescent chemosensors for the highly efficient detection of Hg(2+) ions, pH, and temperatures with tunable detection sensitivity. Compared to reaction-based small molecule Hg(2+) probes in previous literature reports, the integration of stimuli-responsive block copolymers with well-developed small molecule-based selective sensing moieties in the current study are expected to exhibit preferred advantages including enhanced detection sensitivity, water dispersibility, biocompatibility, facile incorporation into devices, and the ability of further functionalization for targeted imaging and detection.
Centralized Duplicate Removal Video Storage System with Privacy Preservation in IoT.
Yan, Hongyang; Li, Xuan; Wang, Yu; Jia, Chunfu
2018-06-04
In recent years, the Internet of Things (IoT) has found wide application and attracted much attention. Since most of the end-terminals in IoT have limited capabilities for storage and computing, it has become a trend to outsource the data from local to cloud computing. To further reduce the communication bandwidth and storage space, data deduplication has been widely adopted to eliminate the redundant data. However, since data collected in IoT are sensitive and closely related to users' personal information, the privacy protection of users' information becomes a challenge. As the channels, like the wireless channels between the terminals and the cloud servers in IoT, are public and the cloud servers are not fully trusted, data have to be encrypted before being uploaded to the cloud. However, encryption makes the performance of deduplication by the cloud server difficult because the ciphertext will be different even if the underlying plaintext is identical. In this paper, we build a centralized privacy-preserving duplicate removal storage system, which supports both file-level and block-level deduplication. In order to avoid the leakage of statistical information of data, Intel Software Guard Extensions (SGX) technology is utilized to protect the deduplication process on the cloud server. The results of the experimental analysis demonstrate that the new scheme can significantly improve the deduplication efficiency and enhance the security. It is envisioned that the duplicated removal system with privacy preservation will be of great use in the centralized storage environment of IoT.
Wilson, Anna; Goldberg, Tony; Marcquenski, Susan; Olson, Wendy; Goetz, Frederick; Hershberger, Paul; Hart, Lucas M.; Toohey-Kurth, Kathy
2014-01-01
Viral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV.
SAMPA Chip: the New 32 Channels ASIC for the ALICE TPC and MCH Upgrades
NASA Astrophysics Data System (ADS)
Adolfsson, J.; Ayala Pabon, A.; Bregant, M.; Britton, C.; Brulin, G.; Carvalho, D.; Chambert, V.; Chinellato, D.; Espagnon, B.; Hernandez Herrera, H. D.; Ljubicic, T.; Mahmood, S. M.; Mjörnmark, U.; Moraes, D.; Munhoz, M. G.; Noël, G.; Oskarsson, A.; Osterman, L.; Pilyar, A.; Read, K.; Ruette, A.; Russo, P.; Sanches, B. C. S.; Severo, L.; Silvermyr, D.; Suire, C.; Tambave, G. J.; Tun-Lanoë, K. M. M.; van Noije, W.; Velure, A.; Vereschagin, S.; Wanlin, E.; Weber, T. O.; Zaporozhets, S.
2017-04-01
This paper presents the test results of the second prototype of SAMPA, the ASIC designed for the upgrade of read-out front end electronics of the ALICE Time Projection Chamber (TPC) and Muon Chamber (MCH). SAMPA is made in a 130 nm CMOS technology with 1.25 V nominal voltage supply and provides 32 channels, with selectable input polarity, and three possible combinations of shaping time and sensitivity. Each channel consists of a Charge Sensitive Amplifier, a semi-Gaussian shaper and a 10-bit ADC; a Digital Signal Processor provides digital filtering and compression capability. In the second prototype run both full chip and single test blocks were fabricated, allowing block characterization and full system behaviour studies. Experimental results are here presented showing agreement with requirements for both the blocks and the full chip.
CDL description of the CDC 6600 stunt box
NASA Technical Reports Server (NTRS)
Hertzog, J. B.
1971-01-01
The CDC 6600 central memory control (stunt box) is described utilizing CDL (Computer Design Language), block diagrams, and text. The stunt box is a clearing house for all central memory references from the 6600 central and peripheral processors. Since memory requests can be issued simultaneously, the stunt box must be capable of assigning priorities to requests, of labeling requests so that the data will be distributed correctly, and of remembering rejected addresses due to memory conflicts.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Werpy, Todd A.; Holladay, John E.; White, James F.
2004-11-01
This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol. In addition to building blocks, themore » report outlines the central technical barriers that are preventing the widespread use of biomass for products and chemicals.« less
Seismic Evidence for a Geosuture between the Yangtze and Cathaysia Blocks, South China
He, Chuansong; Dong, Shuwen; Santosh, M.; Chen, Xuanhua
2013-01-01
South China, composed of the Yangtze and Cathaysia Blocks and the intervening Jiangnan orogenic belt, has been central to the debate on the tectonic evolution of East Asia. Here we investigate the crustal structure and composition of South China from seismic data employing the H-k stacking technique. Our results show that the composition and seismic structure of the crust in the Jiangnan orogenic belt are identical to those of the Cathaysia Block. Our data reveal a distinct contrast in the crustal structure and composition between the two flanks of the Jiujiang-Shitai buried fault. We propose that the Jiujiang-Shitai buried fault defines a geosuture between the Yangtze and Cathaysia Blocks, and that the felsic lower crust of the Cathaysia Block and the Jiangnan orogenic belt may represent fragments derived from the Gondwana supercontinent. PMID:23857499
Brushed block copolymer micelles with pH-sensitive pendant groups for controlled drug delivery.
Lee, Hyun Jin; Bae, Younsoo
2013-08-01
To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers. Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles. Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.
Factors blocking the development of north - central Rzeszów
NASA Astrophysics Data System (ADS)
Rybka, Adam; Mazur, Rafał
2017-12-01
Rzeszów is one of the best developing cities in Poland. Once the small HQ of a principality - due to complicated historical conditioning - it has now become a place where an increasing number of people choose to live. The city with its bursting life, streets and squares starts and ends, however, in an area which only a few dozen years ago still catered for one fifth of the current population. The main reason for this phenomenon is the presence of spatial barriers, which significantly limit the development of the central urban area. This article analyzes the elements, which block the development of the north-central part of Rzeszów. An appropriate diagnosis of the problem may in the future allow the right actions in urban planning to be taken in order to cross these barriers. This may lead to the future development of areas with huge urbanization potential. Investments undertaken by city authorities to develop the northern peripheries of Rzeszów may trigger the development of the central district in this direction. This may occur as a result of concrete design interventions. The new part of the central district should have the scale and proportions of urban space that answer to the needs of a dynamically developing capital of the Podkarpacie region.
2016-08-09
A test of a small-scale starshade model (58 cm), made from metal, in a dry lake bed in central Nevada's Smith Creek, took place from May to June 2014. Nineteen different versions of the miniaturized starshade were tested over five days. The tests revealed that a starshade, or external occulter, is capable of blocking starlight to a degree that reveals the relatively dim reflected light of a planet next to its brighter star. Like holding your hand up to block sunlight, the starshade works to block excessive starlight from the "eyes" of a space telescope like Hubble. http://photojournal.jpl.nasa.gov/catalog/PIA20902
Duarte, C B; Rosario, L M; Sena, C M; Carvalho, A P
1993-03-01
In adrenal chromaffin cells, depolarization-evoked Ca2+ influx and catecholamine release are partially blocked by blockers of L-type voltage-sensitive Ca2+ channels. We have now evaluated the sensitivity of the dihydropyridine-resistant components of Ca2+ influx and catecholamine release to a toxin fraction (FTX) from the funnel-web spider poison, which is known to block P-type channels in mammalian neurons. FTX (1:4,000 dilution, with respect to the original fraction) inhibited K(+)-depolarization-induced Ca2+ influx by 50%, as monitored with fura-2, whereas nitrendipine (0.1-1 microM) and FTX (3:3), a synthetic FTX analogue (1 mM), blocked the [Ca2+]i transients by 35 and 30%, respectively. When tested together, FTX and nitrendipine reduced the [Ca2+]i transients by 70%. FTX or nitrendipine reduced adrenaline and noradrenaline release by approximately 80 and 70%, respectively, but both substances together abolished the K(+)-evoked catecholamine release, as measured by HPLC. The omega-conotoxin GVIA (0.5 microM) was without effect on K(+)-stimulated 45Ca2+ uptake. Our results indicate that FTX blocks dihydropyridine- and omega-conotoxin-insensitive Ca2+ channels that, together with L-type voltage-sensitive Ca2+ channels, are coupled to catecholamine release.
Photo-inducible Crosslinked Nanoassemblies for pH-Controlled Drug Release
Dickerson, Matthew; Winquist, Nickolas; Bae, Younsoo
2014-01-01
Purpose To control drug release from block copolymer nanoassemblies by variation in the degree of photo-crosslinking and inclusion of acid sensitive linkers. Methods Poly(ethylene glycol)-poly(aspartate-hydrazide-cinnamate) (PEG-CNM) block copolymers were prepared and conjugated with a model drug, doxorubicin (DOX), through acid sensitive hydrazone linkers. The block copolymers formed photo-inducible, self-assembled nanoassemblies (piSNAs), which were used to produce photo-inducible crosslinked nanoassemblies (piCNAs) through UV crosslinking. The nanoassemblies were characterized to determine particle size, surface charge, pH- and crosslinking-dependent DOX release, in vitro cytotoxicity, and intracellular uptake as a function of photo-crosslinking degree. Results Nanoassemblies with varying photo-crosslinking degrees were successfully prepared while retaining particle size and surface charge. Photo-crosslinking caused no noticeable change in DOX release from the nanoassemblies at pH 7.4, but the DOX-loaded nanoassemblies modulated drug release as a function of crosslinking at pH 6.0. The nanoassemblies showed similar cytotoxicity regardless of crosslinking degrees, presumably due to the low cellular uptake and cell nucleus drug accumulation. Conclusion Photo-crosslinking is useful to control drug release from pH-sensitive block copolymer nanoassemblies as a function of crosslinking without altering the particle properties, and thus providing unique tools to investigate the pharmaceutical effects of drug release on cellular response. PMID:24254196
Polymeric micellar pH-sensitive drug delivery system for doxorubicin.
Hrubý, Martin; Konák, Cestmír; Ulbrich, Karel
2005-03-02
A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.
Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro
Russo, Raúl E; Nagy, Frédéric; Hounsgaard, Jørn
1998-01-01
The role of inhibition in control of plateau-generating neurones in the dorsal horn was studied in an in vitro preparation of the spinal cord of the turtle. Ionotropic and metabotropic inhibition was found to condition the expression of plateau potentials. Blockade of γ-aminobutyric acid (GABAA) and glycine receptors by their selective antagonists bicuculline (10-50 μM) and strychnine (5-20 μM) enhanced the excitatory response to stimulation of the dorsal root and facilitated the expression of plateau potentials. Bicuculline and strychnine also facilitated the generation of plateau potentials in response to depolarizing current pulses, suggesting the presence of tonic ionotropic inhibitory mechanisms in turtle spinal cord slices. Activation of GABAB receptors also inhibited plateau-generating neurones. The selective agonist baclofen (5-50 μM) inhibited wind-up of the response to repeated depolarizations induced synaptically or by intracellular current pulses. Baclofen reduced afferent synaptic input. This effect was not affected by bicuculline or strychnine and was blocked by the selective GABAB receptor antagonist 2-hydroxysaclofen (2-OH-saclofen, 100-400 μM). Postsynaptically, baclofen inhibited plateau properties. Activation of GABAB receptors produced a hyperpolarization (7.0 ± 0.5 mV, mean ± s.e.m., n= 29) with an associated decrease in input resistance (22.7 ± 3.1 %, n= 24). These effects were blocked by extracellular Ba2+ (1-2 mM). When the baclofen-induced hyperpolarization and shunt were compensated for by adjusting the bias current and the strength of the stimulus, baclofen still inhibited generation of plateau potentials. Wind-up and after-discharges were also inhibited by baclofen. These effects remained in the presence of tetrodotoxin (1 μM) and were antagonized by 2-OH-saclofen. The inhibition of plateau properties was observed even when the baclofen-induced hyperpolarization and shunt were blocked by Ba2+ and when potassium channels were blocked by Ba2+ (3 mM), tetraethylammonium (TEA, 15 mM) and apamin (0.25-0.5 μM). The baclofen-sensitive component of the plateau potential was reduced by nifedipine (10 μM), suggesting a modulation of postsynaptic L-type Ca2+ channels. We suggest that inhibitory regulation of plateau properties plays a role in somatosensory processing in the dorsal horn. The inhibitory control of wind-up and after-discharges may be particularly significant in physiological and therapeutic control of central sensitization to pain. PMID:9503338
NASA Astrophysics Data System (ADS)
Gülyüz, Erhan; Özkaptan, Murat; Langereis, Cor G.; Kaymakcı, Nuretdin
2017-04-01
Closures of Paleo- (largely Paleozoic) and Neo-Tethys (largely Mesozoic) Oceans developed between Europe, Africa and Arabia are the main driving mechanisms behind the post-Triassic tectonics, magmatism and metamorphism occurred in Anatolia. Although various scenarios have been suggested for the timing and characteristics of the subduction systems, it is largely accepted that these blocks are progressively collided and amalgamated along the northern (İzmir-Ankara-Erzincan suture zone; IAESZ) and the southern (Bitlis-Zagros suture zone; BZSZ) branches of Neo-Tethys Ocean. The geographic positions of these suture zones in Anatolia are marked by imbricated stacks of largely metamorphosed remnants of the Paleo- and Neo-Tethys Oceans. In addition to this tectonic frame, the existence of another suture zone within the northern branch of the Neo-Tethys separating the Kırşehir Block, a triangular (200km*200km*200km) continental domain represented by mainly high-pressure (HP) meta-sedimentary rocks, from the Taurides, is proposed and named as Intra-Tauride Suture Zone (ITSZ). Although traces of the Neo-Tethyan closure and continental collisions in the Central Anatolia are recorded (1) in sedimentary basins as fold and thrust belt developments (as northern Taurides fold and thrust belt along IAESZ and central Taurides fold and thrust belt along ITSZ), (2) on metamorphic rocks with Late Cretaceous to Late Paleocene peak metamorphism, and (3) on magmatic rocks with Late Cretaceous - Paleocene arc-related intrusions and post-Paleocene post-collisional magmatism, timing of these continental collisions are discussed in limited studies and furthermore they indicate a large time span (post-Paleocene to Miocene) for the collisions. This study aims to date continental collisions occurred in Central Anatolia qualitatively. In this regard, low-temperature thermo-chronometric and paleo-magnetic studies were conducted on the sedimentary units cropped-out along the western and north-western margins of the Kırşehir Block where two suture zones coincided (IAESZ & ITSZ). Although, thermo-chronometric studies have not been completely conducted, initial results consistently indicate Oligocene-Early Miocene continental uplift along the western margin of the Kırşehir Block. In keeping with thermo-chronometric results, paleo-magnetic samples (400 cores) taken systematically from upper Cretaceous to Miocene sedimentary units exposed along the IAESZ and ITSZ suggest that concentration of vertical block rotations are accumulated in Oligocene-Early Miocene time interval indicating the timing of main deformation events. Based on the paleo-magnetic and low-temperature thermo-chronometric results, we propose that continental collisions along IAESZ and ITSZ in the Central Anatolia occurred during Oligocene - Early Miocene time interval which might also correspond to the commencement of continental deposition and the base of regional unconformities exposed in the region.
Central Sensitization Syndrome and the Initial Evaluation of a Patient with Fibromyalgia: A Review
Fleming, Kevin C.; Volcheck, Mary M.
2015-01-01
In both primary care and consultative practices, patients presenting with fibromyalgia (FM) often have other medically unexplained somatic symptoms and are ultimately diagnosed as having central sensitization (CS). Central sensitization encompasses many disorders where the central nervous system amplifies sensory input across many organ systems and results in myriad symptoms. A pragmatic approach to evaluate FM and related symptoms, including a focused review of medical records, interviewing techniques, and observations, is offered here, giving valuable tools for identifying and addressing the most relevant symptoms. At the time of the clinical evaluation, early consideration of CS may improve the efficiency of the visit, reduce excessive testing, and help in discerning between typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of pain and neurophysiology and sensitization often proves helpful. PMID:25973272
Preliminary correlations of MAGSAT anomalies with tectonic features of Africa
Hastings, David A.
1982-01-01
An overview of the MAGSAT scalar anomaly map for Africa has suggested a correlation of MAGSAT anomalies with major crustal blocks of uplift or depression and different degrees of regional metamorphism. The strongest MAGSAT anomalies in Africa are closely correlated spatially with major tectonic features. Although a magnetic anomaly caused by a rectangular crustal block would be offset from the block's center by the effects of magnetic inclination, an anomaly caused by real crustal blocks of varying uplift, depression, and degree of regional metamorphism would be located nearer to the locus of greatest vertical movement and highest grade of metamorphism. Thus, the Bangui anomaly may be caused by a central old Precambrian shield, flanked to the north and south by two relatively young sedimentary basins.
Variation in sensitivity, absorption and density of the central rod distribution with eccentricity.
Tornow, R P; Stilling, R
1998-01-01
To assess the human rod photopigment distribution and sensitivity with high spatial resolution within the central +/-15 degrees and to compare the results of pigment absorption, sensitivity and rod density distribution (number of rods per square degree). Rod photopigment density distribution was measured with imaging densitometry using a modified Rodenstock scanning laser ophthalmoscope. Dark-adapted sensitivity profiles were measured with green stimuli (17' arc diameter, 1 degrees spacing) using a T ubingen manual perimeter. Sensitivity profiles were plotted on a linear scale and rod photopigment optical density distribution profiles were converted to absorption profiles of the rod photopigment layer. Both the absorption profile of the rod photopigment and the linear sensitivity profile for green stimuli show a minimum at the foveal center and increase steeply with eccentricity. The variation with eccentricity corresponds to the rod density distribution. Rod photopigment absorption profiles, retinal sensitivity profiles, and the rod density distribution are linearly related within the central +/-15 degrees. This is in agreement with theoretical considerations. Both methods, imaging retinal densitometry using a scanning laser ophthalmoscope and dark-adapted perimetry with small green stimuli, are useful for assessing the central rod distribution and sensitivity. However, at present, both methods have limitations. Suggestions for improving the reliability of both methods are given.
NASA Astrophysics Data System (ADS)
Wang, S.; Zhang, G.; Dong, D.; Wang, Y.
2016-12-01
In order to understand the paleoenvironment of the Early Cambrian black shale deposition in the western part of the Yangtze Block, geochemical and organic carbon isotopic studies have been performed on two wells that have drilled through the Qiongzhusi Formation in the central and southeastern parts of Sichuan Basin. It shows that the lowest part of the Qiongzhusi Formation has high TOC abundance, while the middle and upper parts display relative low TOC content. Redox-sensitive element (Mo) and trace elemental redox indices (e.g., Ni/Co, V/Cr, U/Th and V/(V+Ni)) suggest that the high-TOC layers were deposited under anoxic conditions, whereas the low-TOC layers under relatively dysoxic/oxic conditions. The relationship of the enrichment factors of Mo and U further shows a transition from suboxic low-TOC layers to euxinic high-TOC layers. On the basis of the Mo-TOC relationship, the Qiongzhusi Formation black shales were deposited in a basin under moderately restricted conditions. Organic carbon isotopes display temporal variations in the Qiongzhusi Formation, with a positive excursion of δ13Corg values in the lower part and a continuous positive shift in the middle and upper parts. All these geochemical and isotopic criteria indicate a paleoenvironmental change from bottom anoxic to middle and upper dysoxic/oxic conditions for the Qiongzhusi Formation black shales. The correlation of organic carbon isotopic data for the Lower Cambrian black shales in different regions of the Yangtze Block shows consistent positive excursion of δ13Corg values in the lower part for each section. This excursion can be ascribed to the widespread Early Cambrian transgression in the Yangtze Block, under which black shales were deposited.
Anderson, W; Molina, E; Rentz, J; Hirschowitz, B I
1982-09-01
Gastric acid and pepsin secreted in 3 hr and antral gastrin released in response to vagal excitation induced by 2-deoxy-D-glucose (2DG), 625 mumol/kg i.v., were studied in six conscious trained gastric fistula dogs. During a 2-hr infusion, Met-enkephalin (96 nmol/kg/hr; delta receptor) reduced the 2DG response by 50%; when the enkephalin was stopped there was a rapid rebound to peak values. Met-enkephalin also blocked the release of gastrin in the first 15 min. By itself, Met-enkephalin did not stimulate secretion and slightly depressed gastrin. By contrast, morphine (96 nmol/kg/hr; mu receptor) augmented and sustained the 2DG gastric acid secretory response. This effect was blocked by naloxone. Morphine alone caused a small rise in serum gastrin after 90 min, followed by a delayed gastric acid secretion of about 30% of the peak 2DG response. Naloxone, a mu opiate antagonist (mu/delta, 27:1), also inhibited the 2DG gastric secretory response by about 50% and augmented the Met-enkephalin inhibition of secretion without blocking either the secretory rebound or the effect on gastrin release. None of the three opiates changed the direct cholinergic gastric secretory or gastrin-releasing effects of bethanechol. Thus, vagal stimulation of the stomach involves pathways which can be influenced by both mu and delta opiates, with apparently opposite effects, proximal to the level of acetylcholine action on the gastric mucosa. The central and peripheral control points in the activation of the stomach via the vagus which are sensitive to opiates have yet to be located and explained.
Bradaïa, A; Trouslard, J
2002-01-01
Using patch clamp recordings on neonatal rat spinal cord slices, we have looked for the presence of α-bungarotoxin-sensitive nicotinic ACh receptors (nAChRs) on sympathetic preganglionic neurones (SPNs) surrounding the central canal of the spinal cord (lamina X) and examined whether they were implicated in a fast cholinergic synaptic transmission. SPNs were identified either by their morphology using biocytin in the recording electrode and/or by antidromic stimulation of the ventral rootlets. The selective α7-containing nAChR (α7*nAChR) agonist choline (10 mm) induced a fast, rapidly desensitizing inward current, which was fully blocked by α-bungarotoxin (α-BgT; 50 nm) and strychnine (1 μm), two antagonists of α7*nAChRs. The I-V relationship of the choline-induced current showed a strong inward-going rectification. Electrically evoked excitatory postsynaptic currents (eEPSCs) could be recorded. At -60 mV, eEPSCs peaked at -26.2 pA and decayed monoexponentially with a mean time constant of 8.5 ms. The current-voltage relationship for eEPSCs exhibited a strong inward rectification and a reversal potential close to 0 mV, compatible with a non-selective cationic current. The appearance of eEPSCs was entirely suppressed by the application of 100 μm ACh or nicotine. Choline (10 mm) and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 100 μm) both reduced the amplitude of eEPSCs, whereas cytisine (100 μm) had no effect. Strychnine (1 μm) and α-BgT (50 nm) both suppressed the eEPSCs. Blocking the P2X purinergic and 5-HT3 receptors had no effect on eEPSCs. DMPP induced four types of current, which differed in their onset and desensitization rate. The most frequently encountered responses were insensitive to the action of strychnine and α-BgT, and were reproduced by ACh and nicotine but not by cytisine. We conclude that SPNs of the lamina X express several classes of nAChRs and in particular α-BgT-sensitive nAChRs. This is the first demonstration in a mammalian spinal cord preparation of a fast cholinergic neurotransmission in which α-BgT-sensitive nicotinic receptors are involved. PMID:12411519
PSO4: a novel gene involved in error-prone repair in Saccharomyces cerevisiae.
Henriques, J A; Vicente, E J; Leandro da Silva, K V; Schenberg, A C
1989-09-01
The haploid xs9 mutant, originally selected for on the basis of a slight sensitivity to the lethal effect of X-rays, was found to be extremely sensitive to inactivation by 8-methoxypsoralen (8MOP) photoaddition, especially when cells are treated in the G2 phase of the cell cycle. As the xs9 mutation showed no allelism with any of the 3 known pso mutations, it was now given the name of pso4-1. Regarding inactivation, the pso4-1 mutant is also sensitive to mono- (HN1) or bi-functional (HN2) nitrogen mustards, it is slightly sensitive to 254 nm UV radiation (UV), and shows nearly normal sensitivity to 3-carbethoxypsoralen (3-CPs) photoaddition or methyl methanesulfonate (MMS). Regarding mutagenesis, the pso4-1 mutation completely blocks reverse and forward mutations induced by either 8MOP or 3CPs photoaddition, or by gamma-rays. In the cases of UV, HN1, HN2 or MMS treatments, while reversion induction is still completely abolished, forward mutagenesis is only partially inhibited for UV, HN1, or MMS, and it is unaffected for HN2. Besides severely inhibiting induced mutagenesis, the pso4-1 mutation was found to be semi-dominant, to block sporulation, to abolish the diploid resistance effect, and to block induced mitotic recombination, which indicates that the PSO4 gene is involved in a recombinational pathway of error-prone repair, comparable to the E. coli SOS repair pathway.
Oliveira, Nidia M M; Broom, Annette K; Mackenzie, John S; Smith, David W; Lindsay, Michael D A; Kay, Brian H; Hall, Roy A
2006-07-01
We describe the development of an epitope-blocking enzyme-linked immunosorbent assay (ELISA) for the sensitive and rapid detection of antibodies to Ross River virus (RRV) in human sera and known vertebrate host species. This ELISA provides an alternative method for the serodiagnosis of RRV infections.
Assessing housing growth when census boundaries change
Alexandra D. Syphard; Susan I. Stewart; Jason McKeefry; Roger B. Hammer; Jeremy S. Fried; Sherry Holcomb; Volker C. Radeloff
2009-01-01
The US Census provides the primary source of spatially explicit social data, but changing block boundaries complicate analyses of housing growth over time. We compared procedures for reconciling housing density data between 1990 and 2000 census block boundaries in order to assess the sensitivity of analytical methods to estimates of housing growth in Oregon. Estimates...
Fear-Potential Startle as a Model System for Analyzing Learning and Memory
1988-09-21
connection between the central nucleus of the amygdala and the nucleus reticularis pontis caudalis, an obligatory part of the startle pathway. Because we...Miserendino, M and Davis, M. A direct pathway from the central nucleus of the amygdala to the region of the nucleus reticularis pontis caudalis critical for...blocked by drugs that decrease anxiety in humans as well as by lesions of the central nucleus of the amygdala, an area of the brain known to be critical for
Kallupi, Marsida; Wee, Sunmee; Edwards, Scott; Whitfield, Tim W.; Oleata, Christopher S.; Luu, George; Schmeichel, Brooke E.; Koob, George F.; Roberto, Marisa
2013-01-01
Background Studies have demonstrated an enhanced dynorphin/kappa-opioid receptor (KOR) system following repeated cocaine exposure, but few reports have focused on neuroadaptations within the central amygdala (CeA). Methods We identified KOR-related physiological changes in the CeA following escalation of cocaine self-administration in rats. We used in vitro slice electrophysiological (intracellular and whole-cell recordings) methods to assess whether differential cocaine access in either 1h (short access, ShA) or 6h (long access, LgA) sessions induced plasticity at CeA GABAergic synapses, or altered the sensitivity of these synapses to KOR agonism (U50488) or antagonism (nor-BNI). We then determined the functional effects of CeA KOR blockade in cocaine-related behaviors. Results Baseline evoked GABAergic transmission was enhanced in the CeA from ShA and LgA rats compared to cocaine-naïve rats. Acute cocaine (1 uM) application significantly decreased GABA release in all groups (naïve, ShA, and LgA rats). Application of U50488 (1 uM) significantly decreased GABAergic transmission in the CeA from naïve rats, but increased it in LgA rats. Conversely, nor-BNI (200 nM) significantly increased GABAergic transmission in the CeA from naïve rats, but decreased it in LgA rats. Nor-BNI did not alter the acute cocaine-induced inhibition of GABAergic responses. Finally, CeA microinfusion of nor-BNI blocked cocaine-induced locomotor sensitization and attenuated the heightened anxiety-like behavior observed during withdrawal from chronic cocaine exposure in the defensive burying paradigm. Conclusion Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction. PMID:23751206
Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying
2017-08-01
Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.
Yamamoto, Seiichi; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Ichikawa, Kazuhiro; Nakao, Motonao; Kato, Katsuhiko; Hatazawa, Jun
2016-10-01
Positron emission tomography (PET) has high sensitivity for imaging radioactive tracer distributions in subjects. However, it is not possible to image free radical distribution in a subject by PET. Since free radicals are quite reactive, they are related to many diseases, including but not limited to cancer, inflammation, strokes, and heart disease. The Overhauser enhanced magnetic resonance imaging (OMRI) is so far the only method that images free radical distribution in vivo. By combining PET and OMRI, a new hybrid imaging modality might be developed that can simultaneously image the radioactive tracer and free radical distributions. For this purpose, the authors developed a PET/OMRI combined system for small animals. The developed PET/OMRI system used an optical fiber-based PET system combined with a permanent magnet-based OMRI system. The optical fiber-based PET system uses flexible optical fiber bundles. Eight optical fiber-based block detectors were arranged in a 56 mm diameter ring to form a PET system. The LGSO blocks were located inside the field-of-view (FOV) of the OMRI, and the position sensitive photomultiplier tubes were positioned behind the OMRI to minimize the interference between the PET and the OMRI. The OMRI system used a 0.0165 T permanent magnet. The system has an electron spin resonance coil to enhance the MRI signal using the Overhauser effect to image the free radical in the FOV of the PET/OMRI system. The spatial resolution and sensitivity of the optical fiber-based PET system were 1.2 mm FWHM and 1.2% at the central FOV, respectively. The OMRI system imaged the distribution of a nitroxyl radical (NXR) solution. The interference between PET and OMRI was small. Simultaneous imaging of the positron radiotracer and the NXR solution was successfully conducted with the developed PET/OMRI system for phantom and small animal studies. The authors developed a PET/OMRI combined system with the potential to provide interesting new results in molecular imaging research, such as in vivo molecular and free radical distributions.
Zhang, Yuxuan; Ramirez, Rocio A; Li, Hongdi; Liu, Shitao; An, Shaohui; Wang, Chao; Baghaei, Hossain; Wong, Wai-Hoi
2010-02-01
A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.
Central Role of Pyruvate Kinase in Carbon Co-catabolism of Mycobacterium tuberculosis*
Noy, Tahel; Vergnolle, Olivia; Hartman, Travis E.; Rhee, Kyu Y.; Jacobs, William R.; Berney, Michael; Blanchard, John S.
2016-01-01
Mycobacterium tuberculosis (Mtb) displays a high degree of metabolic plasticity to adapt to challenging host environments. Genetic evidence suggests that Mtb relies mainly on fatty acid catabolism in the host. However, Mtb also maintains a functional glycolytic pathway and its role in the cellular metabolism of Mtb has yet to be understood. Pyruvate kinase catalyzes the last and rate-limiting step in glycolysis and the Mtb genome harbors one putative pyruvate kinase (pykA, Rv1617). Here we show that pykA encodes an active pyruvate kinase that is allosterically activated by glucose 6-phosphate (Glc-6-P) and adenosine monophosphate (AMP). Deletion of pykA prevents Mtb growth in the presence of fermentable carbon sources and has a cidal effect in the presence of glucose that correlates with elevated levels of the toxic catabolite methylglyoxal. Growth attenuation was also observed in media containing a combination of short chain fatty acids and glucose and surprisingly, in media containing odd and even chain fatty acids alone. Untargeted high sensitivity metabolomics revealed that inactivation of pyruvate kinase leads to accumulation of phosphoenolpyruvate (P-enolpyruvate), citrate, and aconitate, which was consistent with allosteric inhibition of isocitrate dehydrogenase by P-enolpyruvate. This metabolic block could be relieved by addition of the α-ketoglutarate precursor glutamate. Taken together, our study identifies an essential role of pyruvate kinase in preventing metabolic block during carbon co-catabolism in Mtb. PMID:26858255
Allen, Marcus J; Murphey, R K
2007-07-01
The largest central synapse in adult Drosophila is a mixed electro-chemical synapse whose gap junctions require the product of the shaking-B (shak-B) gene. Shak-B(2) mutant flies lack gap junctions at this synapse, which is between the giant fibre (GF) and the tergotrochanteral motor neuron (TTMn), but it still exhibits a long latency response upon GF stimulation. We have targeted the expression of the light chain of tetanus toxin to the GF, to block chemical transmission, in shak-B(2) flies. The long latency response in the tergotrochanteral muscle (TTM) was abolished indicating that the chemical component of the synapse mediates this response. Attenuation of GAL4-mediated labelling by a cha-GAL80 transgene, reveals the GF to be cholinergic. We have used a temperature-sensitive allele of the choline acetyltransferase gene (cha(ts2)) to block cholinergic synapses in adult flies and this also abolished the long latency response in shak-B(2) flies. Taken together the data provide evidence that both components of this mixed synapse are functional and that the chemical neurotransmitter between the GF and the TTMn is acetylcholine. Our findings show that the two components of this synapse can be separated to allow further studies into the mechanisms by which mixed synapses are built and function.
Allen, Marcus J; Murphey, R K
2007-01-01
The largest central synapse in adult Drosophila is a mixed electro-chemical synapse whose gap junctions require the product of the shaking-B (shak-B) gene. Shak-B2 mutant flies lack gap junctions at this synapse, which is between the giant fibre (GF) and the tergotrochanteral motor neuron (TTMn), but it still exhibits a long latency response upon GF stimulation. We have targeted the expression of the light chain of tetanus toxin to the GF, to block chemical transmission, in shak-B2 flies. The long latency response in the tergotrochanteral muscle (TTM) was abolished indicating that the chemical component of the synapse mediates this response. Attenuation of GAL4-mediated labelling by a cha-GAL80 transgene, reveals the GF to be cholinergic. We have used a temperature-sensitive allele of the choline acetyltransferase gene (chats2) to block cholinergic synapses in adult flies and this also abolished the long latency response in shak-B2 flies. Taken together the data provide evidence that both components of this mixed synapse are functional and that the chemical neurotransmitter between the GF and the TTMn is acetylcholine. Our findings show that the two components of this synapse can be separated to allow further studies into the mechanisms by which mixed synapses are built and function. PMID:17650116
Robert S. Boyd; John D. Freeman; James H. Miller; M. Boyd Edwards
1995-01-01
Abstract. Maintenance of biodiversity is becoming a goal of forest management. This study determined effects of broadcast pine release herbicide treatments on plant species richness, diversity, and structural proportions seven years after treatment. Three study blocks were established in central Georgia. Plots 0.6-0.8 ha in size were planted to...
Seismicity and plate tectonics in south central Alaska
NASA Technical Reports Server (NTRS)
Van Wormer, J. D.; Davies, J.; Gedney, L.
1974-01-01
Hypocenter distribution shows that the Benioff zone associated with the Aleutian arc terminates in interior Alaska some 75 km north of the Denali fault. There appears to be a break in the subducting Pacific plate in the Yentna River-Prince William Sound area which separates two seismically independent blocks, similar to the segmented structure reported for the central Aleutian arc.
ION PRODUCING MECHANISM (CHARGE CUPS)
Brobeck, W.W.
1959-04-21
The problems of confining a charge material in a calutron and uniformly distributing heat to the charge is described. The charge is held in a cup of thermally conductive material removably disposed within the charge chamber of the ion source block. A central thermally conducting stem is incorporated within the cup for conducting heat to the central portion of the charge contained within the cup.
NASA Astrophysics Data System (ADS)
Song, Peiping; Ding, Lin; Li, Zhenyu; Lippert, Peter C.; Yue, Yahui
2017-10-01
The origin of the northern Qiangtang block and its Late Paleozoic-Early Mesozoic drift history remain controversial, largely because paleomagnetic constraints from pre-Mesozoic units are sparse and of poor quality. In this paper, we provide a robust and well-dated paleomagnetic pole from the Lower Permian Kaixinling Group lavas on the northern Qiangtang block. This pole suggests that the northern Qiangtang block had a paleolatitude of 21.9 ± 4.7 °S at ca. 296.9 ± 1.9 Ma. These are the first volcanic-based paleomagnetic results from pre-Mesozoic rocks of the Qiangtang block that appear to average secular variation accurately enough to yield a well-determined paleolatitude estimate. This new pole corroborates the hypothesis, first noted on the basis of less rigorous paleomagnetic data, the presence of diamictites, detrital zircon provenance records, and faunal assemblages, that the northern Qiangtang block rifted away from Gondwana prior to the Permian. Previous studies have documented that the northern Qiangtang block accreted to the Tarim-North China continent by Norian time. We calculate a total northward drift of ca. 7000 km over ca. 100 myr, which corresponds to an average south-north plate velocities of ∼7.0 cm/yr. Our results do not support the conclusion that northern Qiangtang has a Laurasian affinity, nor that the central Qiangtang metamorphic belt is an in situ Paleo-Tethys suture. Our analysis, however, does not preclude paleogeographies that interpret the central Qiangtang metamorphic belt as an intra-Qiangtang suture that developed at southernly latitudes outboard of the Gondwanan margin. We emphasize that rigorous paleomagnetic data from Carboniferous units of northern Qiangtang and especially upper Paleozoic units from southern Qiangtang can test and further refine these paleogeographic interpretations.
Hissar-Alai and the Pamirs: Junction and Position in the System of Mobile Belts of Central Asia
NASA Astrophysics Data System (ADS)
Leonov, M. G.; Rybin, A. K.; Batalev, V. Yu.; Matyukov, V. E.; Shchelochkov, G. G.
2018-01-01
The position of the Pamirs and the Hissar-Alai mountainous system in the structure of Central Asia and features of their junction are considered. It is shown that their outer contours and tectonic infrastructure are significantly distinct in the planar pattern: latitudinally linear and arched for the Hissar-Alai and the Pamirs, respectively. These structures logically match those of the Central Asian and Alpine-Himalayan belts, respectively. The Pamir orogen is a relatively autonomous structural element of the crust, which is located discordantly relative to the country lithospheric blocks. Most of the Pamirs (at least, the Northern and Central) probably form a giant allochthon on the ancient basement of the Tarim and Afghan-Tajik blocks. The junction zone of these two "hard" crustal segments is reflected in the transverse Transpamir threshold, which is expressed in the relief, deep structure, and seismicity. The specific geological structure of the junction zone of the Pamirs and Hissar-Alai (systems of the Tarim, Alai, and Afghan-Tajik troughs) is shown. It suggested that this zone is a damper, which significantly neutralizes the dynamic influence of the Pamir and the southernmost elements of the Pamir-Punjab syntax on Hissar-Alai structures.
Wilson, Anna; Goldberg, Tony; Marcquenski, Susan; Olson, Wendy; Goetz, Frederick; Hershberger, Paul; Hart, Lucas
2014-01-01
Viral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV. PMID:24429071
Reflection type skin friction meter
NASA Technical Reports Server (NTRS)
Bandyopadhyay, Promode R. (Inventor); Weinstein, Leonard M. (Inventor)
1993-01-01
A housing block is provided having an upper surface conforming to the test surface of a model or aircraft. An oil film is supplied upstream of a transparent wedge window located in this upper surface by an oil pump system located external to the housing block. A light source located within the housing block supplies a light beam which passes through this transparent window and is reflected back through the transparent window by the upper surface of the oil film to a photo-sensitive position sensor located within the housing. This position sensor allows the slope history of the oil film caused by and aerodynamic flow to be determined. The skin friction is determined from this slope history. Internally located mirrors augment and sensitize the reflected beam as necessary before reaching the position sensor. In addition, a filter may be provided before this sensor to filter the beam.
Krýsová, Hana; Kavan, Ladislav
2018-01-01
For proper function of the negative electrode of dye-sensitized and perovskite solar cells, the deposition of a nonporous blocking film is required on the surface of F-doped SnO2 (FTO) glass substrates. Such a blocking film can minimise undesirable parasitic processes, for example, the back reaction of photoinjected electrons with the oxidized form of the redox mediator or with the hole-transporting medium can be avoided. In the present work, thin, transparent, blocking TiO2 films are prepared by semi-automatic spray pyrolysis of precursors consisting of titanium diisopropoxide bis(acetylacetonate) as the main component. The variation in the layer thickness of the sprayed films is achieved by varying the number of spray cycles. The parameters investigated in this work were deposition temperature (150, 300 and 450 °C), number of spray cycles (20–200), precursor composition (with/without deliberately added acetylacetone), concentration (0.05 and 0.2 M) and subsequent post-calcination at 500 °C. The photo-electrochemical properties were evaluated in aqueous electrolyte solution under UV irradiation. The blocking properties were tested by cyclic voltammetry with a model redox probe with a simple one-electron-transfer reaction. Semi-automatic spraying resulted in the formation of transparent, homogeneous, TiO2 films, and the technique allows for easy upscaling to large electrode areas. The deposition temperature of 450 °C was necessary for the fabrication of highly photoactive TiO2 films. The blocking properties of the as-deposited TiO2 films (at 450 °C) were impaired by post-calcination at 500 °C, but this problem could be addressed by increasing the number of spray cycles. The modification of the precursor by adding acetylacetone resulted in the fabrication of TiO2 films exhibiting perfect blocking properties that were not influenced by post-calcination. These results will surely find use in the fabrication of large-scale dye-sensitized and perovskite solar cells. PMID:29719764
Central sensitization in chronic low back pain: A narrative review.
Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare
2016-11-21
Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.
Characteristics of cholinoreceptors on identified TAN neurons of the ground snail Achatina fulica.
Stepanov, I I; Losev, N A
2000-01-01
The characteristics of cholinoreceptors located on neurons TAN1, TAN2, and TAN3 of the ground snail Achatina fulica were studied by incubation of the central ganglia in a bath with cholinotropic preparations during intracellular recording of background neuron spike activity. Acetylcholine, nicotine, the selective n-cholinoreceptor agonist suberyldicholine, and the selective n-cholinoreceptor agonist 5-methylfurmethide concentration-dependently inhibited background spike activity to the level of complete blockade at concentrations of 500 microM. The m-cholinoblocker metamizil (500 microM) completely prevented the inhibitory activity of concentrations of 5-methylfurmethide of up to 500 microM. The central n-cholinoblocker etherophen (500 microM) completely blocked the inhibitory activity of 500 microM suberyldicholine. However, metamizil and etherophen added separately only partially decreased the inhibitory effects of acetylcholine but could not completely block the effect of acetylcholine. At the same time, mixtures of metamizil and etherophen (500 microM each) completely blocked the inhibition of background spike activity induced by acetylcholine. These results show that both classes of cholinoreceptors act on TAN neurons in the same direction.
Optimized optical clearing method for imaging central nervous system
NASA Astrophysics Data System (ADS)
Yu, Tingting; Qi, Yisong; Gong, Hui; Luo, Qingming; Zhu, Dan
2015-03-01
The development of various optical clearing methods provides a great potential for imaging entire central nervous system by combining with multiple-labelling and microscopic imaging techniques. These methods had made certain clearing contributions with respective weaknesses, including tissue deformation, fluorescence quenching, execution complexity and antibody penetration limitation that makes immunostaining of tissue blocks difficult. The passive clarity technique (PACT) bypasses those problems and clears the samples with simple implementation, excellent transparency with fine fluorescence retention, but the passive tissue clearing method needs too long time. In this study, we not only accelerate the clearing speed of brain blocks but also preserve GFP fluorescence well by screening an optimal clearing temperature. The selection of proper temperature will make PACT more applicable, which evidently broaden the application range of this method.
Research on wastewater reuse planning in Beijing central region.
Jia, H; Guo, R; Xin, K; Wang, J
2005-01-01
The need to implement wastewater reuse in Beijing is discussed. Based on the investigation of the built wastewater reuse projects in Beijing, the differences between small wastewater reuse system and large systems were analyzed according to the technical, economical and social issues. The advantages and disadvantages of the small system and the large system were then given. In wastewater reuse planning in Beijing urban region, the large system was adopted. The rations of reclaimed water for difference land use type, including industrial reuse, municipal reuse, grass irrigation, and scenes water reuse were determined. Then according to the land use information in every block in central Beijing, using GIS techniques, the amounts of the reclaimed water needed in every block were calculated, and the main pipe system of reclaimed water was planned.
Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; ...
2016-05-12
The Virasoro algebra determines all ‘graviton’ matrix elements in AdS 3/CFT 2. We study the explicit exchange of any number of Virasoro gravitons between heavy and light CFT 2 operators at large central charge. These graviton exchanges can be written in terms of new on-shell tree diagrams, organized in a perturbative expansion in h H/c, the heavy operator dimension divided by the central charge. The Virasoro vacuum conformal block, which is the sum of all the tree diagrams, obeys a differential recursion relation generalizing that of the Catalan numbers. Here, we use this recursion relation to sum the on-shell diagramsmore » to all orders, computing the Virasoro vacuum block. Extrapolating to large h H/c determines the Hawking temperature of a BTZ black hole in dual AdS 3 theories.« less
NASA Astrophysics Data System (ADS)
Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu
2016-05-01
The Virasoro algebra determines all `graviton' matrix elements in AdS3/CFT2. We study the explicit exchange of any number of Virasoro gravitons between heavy and light CFT2 operators at large central charge. These graviton exchanges can be written in terms of new on-shell tree diagrams, organized in a perturbative expansion in h H /c, the heavy operator dimension divided by the central charge. The Virasoro vacuum conformal block, which is the sum of all the tree diagrams, obeys a differential recursion relation generalizing that of the Catalan numbers. We use this recursion relation to sum the on-shell diagrams to all orders, computing the Virasoro vacuum block. Extrapolating to large h H /c determines the Hawking temperature of a BTZ black hole in dual AdS3 theories.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-08
... less than 400 meters. $100.00 per acre or fraction thereof for blocks in water depths of 400 meters or... less than 400 meters, and $100.00 per acre or fraction thereof for blocks in water depths of 400 meters... leases in 0 to less than 400 meters of water depth completed to a drilling depth of 20,000 feet TVD SS or...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-02-12
... for blocks in water depths of 400 meters to less than 1,600 meters. Blocks in 400 to less than 800... resulting from this lease sale. Leases in water depths of 400 meters to less than 800 meters will be offered... still may require the full 10-year term. In both the 400-800 and 800-1,600 meter cases, the lease...
Programmable Direct-Memory-Access Controller
NASA Technical Reports Server (NTRS)
Hendry, David F.
1990-01-01
Proposed programmable direct-memory-access controller (DMAC) operates with computer systems of 32000 series, which have 32-bit data buses and use addresses of 24 (or potentially 32) bits. Controller functions with or without help of central processing unit (CPU) and starts itself. Includes such advanced features as ability to compare two blocks of memory for equality and to search block of memory for specific value. Made as single very-large-scale integrated-circuit chip.
Edwards, Steven J; Karner, Charlotta; Trevor, Nicola; Wakefield, Victoria; Salih, Fatima
2015-08-01
Bradycardia [resting heart rate below 60 beats per minute (b.p.m.)] can be caused by conditions affecting the natural pacemakers of the heart, such as sick sinus syndrome (SSS) and atrioventricular (AV) blocks. People suffering from bradycardia may present with palpitations, exercise intolerance and fainting. The only effective treatment for patients suffering from symptomatic bradycardia is implantation of a permanent pacemaker. To appraise the clinical effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber atrial pacemakers for treating symptomatic bradycardia in people with SSS and no evidence of AV block. All databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) were searched from inception to June 2014. A systematic review of the clinical and economic literature was carried out in accordance with the general principles published by the Centre for Reviews and Dissemination. Randomised controlled trials (RCTs) evaluating dual-chamber and single-chamber atrial pacemakers and economic evaluations were included. Pairwise meta-analysis was carried out. A de novo economic model was developed. Of 493 references, six RCTs were included in the review. The results were predominantly influenced by the largest trial DANPACE. Dual-chamber pacing was associated with a statistically significant reduction in reoperation [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.36 to 0.63] compared with single-chamber atrial pacing. The difference is primarily because of the development of AV block requiring upgrade to a dual-chamber device. The risk of paroxysmal atrial fibrillation was also reduced with dual-chamber pacing compared with single-chamber atrial pacing (OR 0.75, 95% CI 0.59 to 0.96). No statistically significant difference was found between the pacing modes for mortality, heart failure, stroke, chronic atrial fibrillation or quality of life. However, the risk of developing heart failure may vary with age and device. The de novo economic model shows that dual-chamber pacemakers are more expensive and more effective than single-chamber atrial devices, resulting in a base-case incremental cost-effectiveness ratio (ICER) of £6506. The ICER remains below £20,000 in probabilistic sensitivity analysis, structural sensitivity analysis and most scenario analyses and one-way sensitivity analyses. The risk of heart failure may have an impact on the decision to use dual-chamber or single-chamber atrial pacemakers. Results from an analysis based on age (> 75 years or ≤ 75 years) and risk of heart failure indicate that dual-chamber pacemakers dominate single-chamber atrial pacemakers (i.e. are less expensive and more effective) in older patients, whereas dual-chamber pacemakers are dominated by (i.e. more expensive and less effective) single-chamber atrial pacemakers in younger patients. However, these results are based on a subgroup analysis and should be treated with caution. In patients with SSS without evidence of impaired AV conduction, dual-chamber pacemakers appear to be cost-effective compared with single-chamber atrial pacemakers. The risk of developing a complete AV block and the lack of tools to identify patients at high risk of developing the condition argue for the implantation of a dual-chamber pacemaker programmed to minimise unnecessary ventricular pacing. However, considerations have to be made around the risk of developing heart failure, which may depend on age and device. This study is registered as PROSPERO CRD42013006708. The National Institute for Health Research Health Technology Assessment programme.
Measurement of Retinal Sensitivity on Tablet Devices in Age-Related Macular Degeneration.
Wu, Zhichao; Guymer, Robyn H; Jung, Chang J; Goh, Jonathan K; Ayton, Lauren N; Luu, Chi D; Lawson, David J; Turpin, Andrew; McKendrick, Allison M
2015-06-01
We compared measurements of central retinal sensitivity on a portable, low-cost tablet device to the established method of microperimetry in age-related macular degeneration (AMD). A customized test designed to measure central retinal sensitivity (within the central 1° radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. The average test duration on PsyPad was 53.9 ± 7.5 seconds, and no significant learning effect was observed over the examinations performed ( P = 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was ±1.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 ± 0.4 dB) and microperimetry (26.1 ± 0.4 dB, P = 0.094), and the 95% limits of agreement between the two measures were between -4.12 and 4.92 dB. The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry. These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented.
Paleozoic tectonics in the eastern part of Central Asian Orogenic Belt
NASA Astrophysics Data System (ADS)
Liu, Yongjiang; Li, Weimin; Feng, Zhiqiang; Neubauer, Franz
2017-04-01
The Central Asian Orogenic Belt (CAOB) is the largest accretionary orogen in the world, which is responsible for considerable Phanerozoic juvenile crustal growth. The NE China and its adjacent areas compose the eastern segment of the CAOB, which is a key area for providing important evidence of the CAOB evolution and understanding the NE Asian tectonics. The eastern segment of the CAOB is composed tectonically of four micro-blocks and four sutures, i.e. Erguna block (EB), Xing'an block (XB), Songliao-Xilinhot block (SXB), Jiamusi block (JB), Xinlin-Xiguitu suture (XXS), Heihe-Hegenshan suture (HHS), Mudanjiang-Yilan suture (MYS) and Solonker-Xar Moron-Changchun-Yanji suture (SXCYS). The EB and XB were amalgamated by westward subduction, oceanic island accretions and final collision in ca. 500 Ma. The XB and SXB were amalgamated by subduction-related Early Paleozoic marginal arc, Late Paleozoic marginal arc and final collision in the late Early Carboniferous to early Late Carboniferous. The JB probably had been attached to the SXB in the Early Paleozoic, but broken apart from the SXB in the Triassic and collided back in the Jurassic. The closure of Paleo-Asian Ocean had experienced a long continue/episodic subduction-accretion processes on margins of the NCC to the south and the SXB to the north from the Early to Late Paleozoic. The final closure happened along the SXCYS, from west Solonker, Sonid Youqi, Kedanshan (Keshenketengqi), Xar Moron River through Songliao Basin via Kailu, Tongliao, Horqin Zuoyizhongqi, Changchun, to the east Panshi, Huadian, Dunhua, Yanji, with a scissors style closure in time from the Late Permian-Early Triassic in the west to the Late Permian-Middle Triassic in the east. The amalgamated blocks should compose a united micro-continent, named as Jiamusi-Mongolia Block (JMB) after Early Carboniferous, which bounded by Mongo-Okhotsk suture to the northwest, Solonker-Xar Moron-Changchun suture to the south and the eastern margin of JB to the east.
Ross, Donald C.
1972-01-01
This petrographic and chemical study is based on reconnaissance sampling of granitic and related gneissic rock in the California Coast and Transverse Ranges. In the Coast Ranges, granitic rocks are restricted to an elongate belt, the Salinian block, between the San Andreas and Sur-Nacimiento fault zones. These rocks have a considerable compositional range, but are dominantly quartz monzonite and granodiorite. Moist of the Salinian block seems to be a structurally coherent basement block of chemically related granitic rocks. However, on both the east and the west sides of the block, gneiss crops out in abundance; these rocks may be structurally separate from the main part of the Salinian block. In the Transverse Ranges, the granitic and related rocks are dominantly of granodiorite composition, and in many areas granitic and gneissic rocks are intimately intermixed.Chemically the rocks of the California Coast and Transverse Ranges are somewhat intermediate in character between those of the east-central part of the Sierra Nevada batholith and those of the western part of the Sierra Nevada batholith and the southern California batholith. Probably the closest similarity is to the east-central Sierra Nevada rocks, but the rocks of the Coast and Transverse Ranges are somewhat higher in Al2O3 and lower in K2O than Sierran rocks of the comparable SiO2 content.Granitic basement rocks of the Salinian block are now anomalously sandwiched between Franciscan terranes. The petrographic and chemical data are compatible with the concept that the Salinian rocks were originally part of the great batholithic belt along the west coast, which is exemplified by the Sierra Nevada hatholith. It also seems most likely that the Salinian block was transported from somewhere south of the Sierra Nevada batholith by large-scale right-lateral movement along the San Andreas fault zone.
NASA Astrophysics Data System (ADS)
Bradley, Kyle E.; Vassilakis, Emmanuel; Hosa, Aleksandra; Weiss, Benjamin P.
2013-01-01
New paleomagnetic data from Early Miocene to Pliocene terrestrial sedimentary and volcanic rocks in Central Greece constrain the history of vertical-axis rotation along the central part of the western limb of the Aegean arc. The present-day pattern of rapid block rotation within a broad zone of distributed deformation linking the right-lateral North Anatolian and Kephalonia continental transform faults initiated after Early Pliocene time, resulting in a uniform clockwise rotation of 24.3±6.5° over a region >250 km long and >150 km wide encompassing Central Greece and the western Cycladic archipelago. Because the published paleomagnetic dataset requires clockwise rotations of >50° in Western Greece after ˜17 Ma, while our measurements resolve no vertical-axis rotation of Central Greece between ˜15 Ma and post-Early Pliocene time, a large part of the clockwise rotation of Western Greece must have occurred during the main period of contraction within the external thrust belt of the Ionian Zone between ˜17 and ˜15 Ma. Pliocene initiation of rapid clockwise rotation in Central and Western Greece reflects the development of the North Anatolia-Kephalonia Fault system within the previously extended Aegean Sea region, possibly in response to entry of dense oceanic lithosphere of the Ionian Sea into the Hellenic subduction zone and consequent accelerated slab rollback. The development of the Aegean geometric arc therefore occurred in two short-duration pulses characterized by rapid rotation and strong regional deformation.
NASA Astrophysics Data System (ADS)
Rosen, David L.; Pendleton, J. David
1995-09-01
Light scattered from optically active spheres was theoretically analyzed for biodetection. The circularly polarized signal of near-forward scattering from circularly dichroic spheres was calculated. Both remote and point biodetection were considered. The analysis included the effect of a circular aperture and beam block at the detector. If the incident light is linearly polarized, a false signal would limit the sensitivity of the biodetector. If the incident light is randomly polarized, shot noise would limit the sensitivity. Suggested improvements to current techniques include a beam block, precise angular measurements, randomly polarized light, index-matching fluid, and larger apertures for large particles.
Synthetic strategy for preparing chiral double-semicrystalline polyether block copolymers
McGrath, Alaina J.; Shi, Weichao; Rodriguez, Christina G.; ...
2014-12-11
Here, we report an effective strategy for the synthesis of semi-crystalline block copolyethers with well-defined architecture and stereochemistry. As an exemplary system, triblock copolymers containing either atactic (racemic) or isotactic ( R or S) poly(propylene oxide) end blocks with a central poly(ethylene oxide) mid-block were prepared by anionic ring-opening procedures. Stereochemical control was achieved by an initial hydrolytic kinetic resolution of racemic terminal epoxides followed by anionic ring-opening polymerization of the enantiopure monomer feedstock. The resultant triblock copolymers were highly isotactic (meso triads [ mm]% ~ 90%) with optical microscopy, differential scanning calorimetry, wide angle x-ray scattering and small anglemore » x-ray scattering being used to probe the impact of the isotacticity on the resultant polymer and hydrogel properties.« less
Weislogel, A.L.; Graham, S.A.; Chang, E.Z.; Wooden, J.L.; Gehrels, G.E.; Yang, H.
2006-01-01
Using detrital zircon geochronology, turbidite deposystems fed from distinct sediment sources can be distinguished within the Songpan-Ganzi complex, a collapsed Middle to Late Triassic turbidite basin of central China. A southern Songpan-Ganzi deposystem initially was sourced solely by erosion of the Qinling-Dabie orogen during early Late Triassic time, then by Qinling-Dabie orogen, North China block, and South China block sources during middle to late Late Triassic time. A northern Songpan-Ganzi system was sourced by erosion of the Qinling-Dabie orogen and the North China block throughout its deposition. These separate deposystems were later tectonically amalgamated to form one complex and then uplifted as the eastern Tibet Plateau. ?? 2006 Geological Society of America.
Techno-economic analysis of supercritical carbon dioxide power blocks
NASA Astrophysics Data System (ADS)
Meybodi, Mehdi Aghaei; Beath, Andrew; Gwynn-Jones, Stephen; Veeraragavan, Anand; Gurgenci, Hal; Hooman, Kamel
2017-06-01
Developing highly efficient power blocks holds the key to enhancing the cost competitiveness of Concentration Solar Thermal (CST) technologies. Supercritical CO2 (sCO2) Brayton cycles have proved promising in providing equivalent or higher cycle efficiency than supercritical or superheated steam cycles at temperatures and scales relevant for Australian CST applications. In this study, a techno-economic methodology is developed using a stochastic approach to determine the ranges for the cost and performance of different components of central receiver power plants utilizing sCO2 power blocks that are necessary to meet the Australian Solar Thermal Initiative (ASTRI) final LCOE target of 12 c/kWh.
Bearing construction for refrigeration compresssor
Middleton, Marc G.; Nelson, Richard T.
1988-01-01
A hermetic refrigeration compressor has a cylinder block and a crankshaft rotatable about a vertical axis to reciprocate a piston in a cylinder on the cylinder block. A separate bearing housing is secured to the central portion of the cylinder block and extends vertically along the crankshaft, where it carries a pair of roller bearings to journal the crankshaft. The crankshaft has a radially extending flange which is journaled by a thrust-type roller bearing above the bearing housing to absorb the vertical forces on the crankshaft so that all three of the roller bearings are between the crankshaft and the bearing housing to maintain and control the close tolerances required by such bearings.
Sato, Eriko; Hagihara, Takashi; Matsumoto, Akikazu
2012-04-01
Block copolymers consisting of readily degradable polyperoxides and non-degradable vinyl polymers as the block segments were successfully synthesized by reversible chain transfer catalyzed polymerization, which is one of living radical polymerization techniques. The block copolymers showed characteristic morphology and wettability being different from the polymer blends. When block copolymers containing polyperoxide and polymethacrylate blocks were heated below 150 °C, the polyperoxide blocks were completely degraded and the polymethacrylate blocks were recovered without degradation. Block copolymers containing a poly(2-ethylhexyl methacrylate) block were then investigated as a dismantlable adhesion material, which requires adequate bonding strength during use and easy debonding on demand. Among the several block copolymers, the one consisting of poly(2-ethylhexyl methacrylate) and polyperoxide from methyl sorbate (PPMS) (M(n) = 4900) exhibited good performance as a pressure-sensitive adhesive (PSA). After heating the test specimens in a temperature range from 60 to 100 °C, PSA performance, which was evaluated by 180° peel strength and shear holding power measurements, was significantly diminished. Especially, after heating at 100 °C for 1 h, spontaneous debonding of some test specimens was observed because of the evolution of volatile acetaldehyde from PPMS.
Weislogel, A.L.; Graham, S.A.; Chang, E.Z.; Wooden, J.L.; Gehrels, G.E.
2010-01-01
To test the idea that the voluminous upper Middle to Upper Triassic turbidite strata in the Songpan-Ganzi complex of central China archive a detrital record of Dabie ultrahigh-pressure (UHP) terrane unroofing, we report 2080 single detrital U-Pb zircon ages by sensitive high-resolution ion microprobe-reverse geometry (SHRIMP-RG) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis from 29 eastern Songpan-Ganzi complex sandstone samples. Low (<0.07) Th/U zircons, consistent with crystallization under UHP conditions, are rare in eastern Songpan-Ganzi complex zircon, and U-Pb ages of low Th/U zircons are incompatible with a Dabie terrane source. An unweighted pair group method with arithmetic mean nearest-neighbor analysis of Kolmogorov-Smirnov two-sample test results reveals that the eastern Songpan-Ganzi complex is not a single contiguous turbidite system but is instead composed of three subsidiary depocenters, each associated with distinct sediment sources. The northeastern depocenter contains zircon ages characterized by Paleozoic and bimodally distributed Precambrian zircon populations, which, together with south-to southeast-directed paleocurrent data, indicate derivation from the retro-side of the Qinling-Dabie (Q-D) collisional orogen wedge. In the central depocenter, the dominantly Paleozoic detrital zircon signature and south-to southwest-oriented paleocurrent indicators reflect a profusion of Paleozoic zircon grains. These data are interpreted to reflect an influx of material derived from erosion of Paleozoic supra-UHP rocks of the Dabie terrane in the eastern Qinling-Dabie orogen, which we speculate may have been enhanced by development of a monsoonal climate. This suggests that erosional unroofing played a significant role in the initial phase of UHP exhumation and likely influenced the petrotectonic and structural evolution of the Qinling-Dabie orogen, as evidenced by compressed Triassic isotherms/grads reported in the Huwan shear zone that bounds the Dabie terrane to the north. The central depocenter deposits reflect a later influx of bimodally distributed Precambrian zircon, signifying either a decrease in the influx of Paleozoic zircon grains due to stalled UHP exhumation and/or dilution of the same influx of Paleozoic zircons by spilling of Precambrian zircon from the northeastern depocenter into the central depocenter basin, perhaps due to infilling and bypass of sediment from the northern depocenter or due to initial collapse and constriction of the eastern Songpan-Ganzi complex basin. The southeastern depocenter of the eastern Songpan-Ganzi complex bears significant Paleozoic, Neoproterozoic, and Paleoproterozoic zircon populations derived from the South China block and Yidun arc complex, likely recording nascent uplift of the Longmenshan deformation belt due to impingement of the Yidun arc complex upon the western margin of the South China block. ?? 2010 Geological Society of America.
Omission P3 after voluntary action indexes the formation of action-driven prediction.
Kimura, Motohiro; Takeda, Yuji
2018-02-01
When humans frequently experience a certain sensory effect after a certain action, a bidirectional association between neural representations of the action and the sensory effect is rapidly acquired, which enables action-driven prediction of the sensory effect. The present study aimed to test whether or not omission P3, an event-related brain potential (ERP) elicited by the sudden omission of a sensory effect, is sensitive to the formation of action-driven prediction. For this purpose, we examined how omission P3 is affected by the number of possible visual effects. In four separate blocks (1-, 2-, 4-, and 8-stimulus blocks), participants successively pressed a right button at an interval of about 1s. In all blocks, each button press triggered a bar on a display (a bar with square edges, 85%; a bar with round edges, 5%), but occasionally did not (sudden omission of a visual effect, 10%). Participants were required to press a left button when a bar with round edges appeared. In the 1-stimulus block, the orientation of the bar was fixed throughout the block; in the 2-, 4-, and 8-stimulus blocks, the orientation was randomly varied among two, four, and eight possibilities, respectively. Omission P3 in the 1-stimulus block was greater than those in the 2-, 4-, and 8-stimulus blocks; there were no significant differences among the 2-, 4-, and 8-stimulus blocks. This binary pattern nicely fits the limitation in the acquisition of action-effect association; although an association between an action and one visual effect is easily acquired, associations between an action and two or more visual effects cannot be acquired concurrently. Taken together, the present results suggest that omission P3 is highly sensitive to the formation of action-driven prediction. Copyright © 2017 Elsevier B.V. All rights reserved.
Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord
NASA Astrophysics Data System (ADS)
Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.
1986-10-01
Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.
Caseras, Xavier; Mataix-Cols, David; An, Suk Kyoon; Lawrence, Natalia S; Speckens, Anne; Giampietro, Vincent; Brammer, Michael J; Phillips, Mary L
2007-09-01
A majority of patients with disgust-related psychiatric disorders such as animal phobias and contamination-related obsessive-compulsive disorder are women. The aim of this functional magnetic resonance imaging (fMRI) study was to examine possible sex differences in neural responses to disgust-inducing stimuli that might help explain this female predominance. Thirty-four healthy adult volunteers (17 women, all right-handed) were scanned while viewing alternating blocks of disgusting and neutral pictures from the International Affective Picture System. Using a partially-silent fMRI sequence, the participants rated their level of discomfort after each block of pictures. Skin conductance responses (SCR) were measured throughout the experiment. All participants completed the Disgust Scale. Both women and men reported greater subjective discomfort and showed more SCR fluctuations during the disgusting picture blocks than during the neutral picture blocks. Women and men also demonstrated a similar pattern of brain response to disgusting compared with neutral pictures, showing activation in the anterior insula, ventrolateral and dorsolateral prefrontal cortices, and visual regions. Compared with men, women had significantly higher disgust sensitivity scores, experienced more subjective discomfort, and demonstrated greater activity in left ventrolateral prefrontal regions. However, these differences were no longer significant when disgust sensitivity scores were controlled for. In healthy adult volunteers, there are significant sex-related differences in brain responses to disgusting stimuli that are irrevocably linked to greater disgust sensitivity scores in women. The implications for disgust-related psychiatric disorders are discussed.
Liu, Spencer S; John, Raymond S
2010-01-01
Ultrasound guidance for regional anesthesia has increased in popularity. However, the cost of ultrasound versus nerve stimulator guidance is controversial, as multiple and varying cost inputs are involved. Sensitivity analysis allows modeling of different scenarios and determination of the relative importance of each cost input for a given scenario. We modeled cost per patient of ultrasound versus nerve stimulator using single-factor sensitivity analysis for 4 different clinical scenarios designed to span the expected financial impact of ultrasound guidance. The primary cost factors for ultrasound were revenue from billing for ultrasound (85% of variation in final cost), number of patients examined per ultrasound machine (10%), and block success rate (2.6%). In contrast, the most important input factors for nerve stimulator were the success rate of the nerve stimulator block (89%) and the amount of liability payout for failed airway due to rescue general anesthesia (9%). Depending on clinical scenario, ultrasound was either a profit or cost center. If revenue is generated, then ultrasound-guided blocks consistently become a profit center regardless of clinical scenario in our model. Without revenue, the clinical scenario dictates the cost of ultrasound. In an ambulatory setting, ultrasound is highly competitive with nerve stimulator and requires at least a 96% success rate with nerve stimulator before becoming more expensive. In a hospitalized scenario, ultrasound is consistently more expensive as the uniform use of general anesthesia and hospitalization negate any positive cost effects from greater efficiency with ultrasound.
NASA Astrophysics Data System (ADS)
Farner, M. J.; Pluhar, C. J.; Carlson, C. W.
2011-12-01
The Walker Lane belt is a highly tectonically active region of dextral shear in western North America. Situated between the margins of the Sierra Nevada microplate and the Basin and Range extension, it extends northward from the Garlock Fault into portions of Southern Oregon. The Walker Lane is characterized by dextral shear accommodated by strike slip faults and left-stepping normal faults (Unruh et al, 2003). Faulting in the Walker Lane accounts for approximately 25% of the relative motion between the North American and Pacific Plates (Reheis and Dixon 1996). The study spans a region where the Sierra Nevada microplate has shed fault-bounded blocks from its eastern margin into the central Walker Lane during the Neogene. These blocks have behaved somewhat independently of one another and the Sierra Nevada as evidenced by spatially-variable magnitudes of vertical-axis rotation. This blurs the boundary of definition between microplate and fault block. One of the key questions regarding Walker Lane deformation is what is the role of rotation with respect to fault blocks and at what rate(s) does rotation occur. The software package SSPX (Cardozo and Allmendinger 2009) is used to examine previously published geodetic data to derive rotation rates in the west-central Walker Lane. A rate of 1.70° ± 0.24°/Ma is determined for Bridgeport Valley, CA based upon strain inversion of the locally-sparse GPS station data in SSPX. This rate is consistent with paleomagnetically-determined rotation rates for ~9.4 Ma members of the Stanislaus Group around Bridgeport Valley, adjacent to the Mina Deflection (e.g. King et al, 2007 and our data). However there are several shortcomings to using currently available GPS data for this purpose. GPS station spacing in many places does not provide spatial resolution of rotation comparable to the paleomagnetic dataset, which in turn limits our ability to examine small lithospheric fault blocks geodetically. The paleomagnetic data shows rotation variations on the scale of <5 km. Thus, due to GPS station spacing, our strain inversion reveals a spatially-averaged rotation for a larger given area and is not able to detect small lithospheric blocks or groups of blocks with anomalously large rotation rates of 7°/Ma or higher. An alternative hypothesis is that rotation rate is variable with time and that large rotations occurred and have slowed or stopped.
ERIC Educational Resources Information Center
Best, Catherine S.; Moffat, Vivien J.; Power, Michael J.; Owens, David G. C.; Johnstone, Eve C.
2008-01-01
Theory of Mind, Weak Central Coherence and executive dysfunction, were investigated as a function of behavioural markers of autism. This was irrespective of the presence or absence of a diagnosis of an autistic spectrum disorder. Sixty young people completed the Social Communication Questionnaire (SCQ), false belief tests, the block design test,…
Ishihara, Keiko; Yan, Ding-Hong
2007-01-01
The outward component of the strong inward rectifier K+ current (IKir) plays a pivotal role in polarizing the membranes of excitable and non-excitable cells and is regulated by voltage-dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low-affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low-affinity block to outward IKir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 μm spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native IKir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low-affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3- to 4-fold greater susceptibility to the low-affinity block than in Kir2.1. Reducing external [K+] shifted the voltage dependences of both the high- and low-affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low-affinity block in mediating outward IKir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low-affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low-affinity block without markedly altering that to the high-affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in two states having different susceptibilities to internal cationic blockers. PMID:17640933
Kinematics of the Southwestern Caribbean from New Geodetic Observations
NASA Astrophysics Data System (ADS)
Ruiz, G.; La Femina, P. C.; Tapia, A.; Camacho, E.; Chichaco, E.; Mora-Paez, H.; Geirsson, H.
2014-12-01
The interaction of the Caribbean, Cocos, Nazca, and South American plates has resulted in a complex plate boundary zone and the formation of second order tectonic blocks (e.g., the North Andean, Choco and Central America Fore Arc blocks). The Panama Region [PR], which is bounded by these plates and blocks, has been interpreted and modeled as a single tectonic block or deformed plate boundary. Previous research has defined the main boundaries: 1) The Caribbean plate subducts beneath the isthmus along the North Panama Deformed Belt, 2) The Nazca plate converges at very high obliquity with the PR and motion is assumed along a left lateral transform fault and the South Panama Deformed Belt, 3) The collision of PR with NW South America (i.e., the N. Andean and Choco blocks) has resulted in the Eastern Panama Deformed Belt, and 4) collision of the Cocos Ridge in the west is accommodated by crustal shortening, Central American Fore Arc translation and deformation across the Central Costa Rican Deformed Belt. In addition, there are several models that suggest internal deformation of this region by cross-isthmus strike-slip faults. Recent GPS observations for the PR indicates movement to the northeast relative to a stable Caribbean plate at rates of 6.9±4.0 - 7.8±4.8 mm a-1 from southern Costa Rica to eastern Panama, respectively (Kobayashi et al., 2014 and references therein). However, the GPS network did not have enough spatial density to estimate elastic strain accumulation across these faults. Recent installation and expansion of geodetic networks in southwestern Caribbean (i.e., Costa Rica, Panama, and Colombia) combined with geological and geophysical observations provide a new input to investigate crustal deformation processes in this complex tectonic setting, specifically related to the PR. We use new and existing GPS data to calculate a new velocity field for the region and to investigate the kinematics of the PR, including elastic strain accumulation on the major plate boundaries. Expanding our GPS observations within these proposed small blocks could allow us to solve for Euler vectors and calculate their rotation, strain accumulation and slip rates on the major fault systems. Our results combined with the local seismicity could help authorities to reduce uncertainties in seismic risk evaluations.
Attalla, Ehab M; Lotayef, Mohamed M; Khalil, Ehab M; El-Hosiny, Hesham A; Nazmy, Mohamed S
2007-06-01
The purpose of this study was to quantify dose distribution errors by comparing actual dose measurements with the calculated values done by the software. To evaluate the outcome of radiation overexposure related to Panama's accident and in response to ensure that the treatment planning systems (T.P.S.) are being operated in accordance with the appropriate quality assurance programme, we studied the central axis and pripheral depth dose data using complex field shaped with blocks to quantify dose distribution errors. Multidata T.P.S. software versions 2.35 and 2.40 and Helax T.P.S. software version 5.1 B were assesed. The calculated data of the software treatment planning systems were verified by comparing these data with the actual dose measurements for open and blocked high energy photon fields (Co-60, 6MV & 18MV photons). Close calculated and measured results were obtained for the 2-D (Multidata) and 3-D treatment planning (TMS Helax). These results were correct within 1 to 2% for open fields and 0.5 to 2.5% for peripheral blocked fields. Discrepancies between calculated and measured data ranged between 13. to 36% along the central axis of complex blocked fields when normalisation point was selected at the Dmax, when the normalisation point was selected near or under the blocks, the variation between the calculated and the measured data was up to 500% difference. The present results emphasize the importance of the proper selection of the normalization point in the radiation field, as this facilitates detection of aberrant dose distribution (over exposure or under exposure).
Huntley, Andrew H; Srbely, John Z; Zettel, John L
2015-02-01
Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.
Ho, B T; Tsai, M J; Wei, J; Ma, M; Saipetch, P
1996-01-01
A new method of video compression for angiographic images has been developed to achieve high compression ratio (~20:1) while eliminating block artifacts which leads to loss of diagnostic accuracy. This method adopts motion picture experts group's (MPEGs) motion compensated prediction to takes advantage of frame to frame correlation. However, in contrast to MPEG, the error images arising from mismatches in the motion estimation are encoded by discrete wavelet transform (DWT) rather than block discrete cosine transform (DCT). Furthermore, the authors developed a classification scheme which label each block in an image as intra, error, or background type and encode it accordingly. This hybrid coding can significantly improve the compression efficiency in certain eases. This method can be generalized for any dynamic image sequences applications sensitive to block artifacts.
Zhan, Yanping; Chen, Guo; Huang, Jian; Hou, Benchao; Liu, Weicheng; Chen, Shibiao
2017-10-01
The aim of the present study was to investigate the effect of intercostal nerve block combined with general anesthesia on the stress response and postoperative recovery in patients undergoing minimally invasive mitral valve surgery (MIMVS). A total of 30 patients scheduled for MIMVS were randomly divided into two groups (n=15 each): Group A, which received intercostal nerve block combined with general anesthesia and group B, which received general anesthesia alone. Intercostal nerve block in group A was performed with 0.5% ropivacaine from T3 to T7 prior to anesthesia induction. In each group, general anesthesia was induced using midazolam, sufentanil, propofol and vecuronium. Central venous blood samples were collected to determine the concentrations of cortisol, glucose, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at the following time points: During central venous catheterization (T 1 ), 5 min prior to cardiopulmonary bypass (T 2 ), perioperative (T 3 ) and 24 h following surgery (T 4 ). Clinical data, including parameters of opioid (sufentanil) consumption, time of mechanical ventilation, duration of intensive care unit (ICU) stay, visual analog scale scores and any complications arising from intercostal nerve block, were recorded. Levels of cortisol, glucose, IL-6 and TNF-α in group A were significantly lower than those in group B at T 2 (all P<0.001; cortisol, P<0.05), T 3 (all P<0.001) and T 4 (all P<0.001; glucose, P<0.05), suggesting that intercostal nerve block combined with general anesthesia may inhibit the stress response to MIMVS. Additionally, intercostal nerve block combined with general anesthesia may significantly reduce sufentanil consumption (P<0.001), promote early tracheal extubation (P<0.001), shorten the duration of ICU stay (P<0.01) and attenuate postoperative pain (P<0.001), compared with general anesthesia alone. Thus, these results suggest that intercostal nerve block combined with general anesthesia conforms to the concept of rapid rehabilitation surgery and may be suitable for clinical practice.
Tramm, Trine; Kyndi, Marianne; Sørensen, Flemming B; Overgaard, Jens; Alsner, Jan
2018-01-01
The influence of intra-tumoral heterogeneity on the evaluation of immunohistochemical (IHC) biomarker expression may affect the analytical validity of new biomarkers substantially and hence compromise the clinical utility. The aim of this study was to examine the influence of intra-tumoral heterogeneity as well as inter-observer variability on the evaluation of various IHC markers with potential prognostic impact in breast cancer (BCL2, E-cadherin, EGFR, EMMPRIN and Ki-67). From each of 27 breast cancer patients, two tumor-containing paraffin blocks were chosen. Intra-tumoral heterogeneity was evaluated (1) within a single tumor-containing paraffin block ('intra-block agreement') by comparing information from a central, a peripheral tissue microarray (TMA) core and a whole slide section (WS), (2) between two different tumor-containing blocks from the same primary tumor ('inter-block agreement') by comparing information from TMA cores (central/peripheral) and WS. IHC markers on WS and TMA cores were evaluated by two observers independently, and agreements were estimated by Kappa statistics. For BCL2, E-cadherin and EGFR, an almost perfect intra- and inter-block agreement was found. EMMPRIN and Ki-67 showed a more heterogeneous expression with moderate to substantial intra-block agreements. For both stainings, there was a moderate inter-block agreement that improved slightly for EMMPRIN, when using WS instead of TMA cores. Inter-observer agreements were found to be almost perfect for BCL2, E-cadherin and EGFR (WS: κ > 0.82, TMAs: κ > 0.90), substantial for EMMPRIN (κ > 0.63), but only fair to moderate for Ki-67 (WS: κ = 0.54, TMAs: κ = 0.33). BCL2, E-cadherin and EGFR were found to be homogeneously expressed, whereas EMMPRIN and Ki-67 showed a more pronounced degree of intra-tumoral heterogeneity. The results emphasize the importance of securing the analytical validity of new biomarkers by examining the intra-tumoral heterogeneity of immunohistochemical stainings applied to TMA cores individually in each type of cancer.
Michael Swyer
2015-02-22
Global Positioning System (GPS) time series from the National Science Foundation (NSF) Earthscope’s Plate Boundary Observatory (PBO) and Central Washington University’s Pacific Northwest Geodetic Array (PANGA). GPS station velocities were used to infer strain rates using the ‘splines in tension’ method. Strain rates were derived separately for subduction zone locking at depth and block rotation near the surface within crustal block boundaries.
Huang, Jie; Ni, Zhongge; Finch, Philip
2017-09-01
Varicella zoster virus reactivation can cause permanent histological changes in the central and peripheral nervous system. Neural inflammatory changes or damage to the dorsal root ganglia sensory nerve fibers during reactivation can lead to postherpetic neuralgia (PHN). For PHN of the first division of the fifth cranial nerve (ophthalmic division of the trigeminal ganglion), there is evidence of inflammatory change in the ganglion and adjacent ocular neural structures. First division trigeminal nerve PHN can prove to be difficult and sometimes even impossible to manage despite the use of a wide range of conservative measures, including anticonvulsant and antidepressant medication. Steroids have been shown to play an important role by suppressing neural inflammatory processes. We therefore chose the trigeminal ganglion as an interventional target for an 88-year-old woman with severe ophthalmic division PHN after she failed to respond to conservative treatment. Under fluoroscopic guidance, a trigeminal ganglion nerve block was performed with lidocaine combined with dexamethasone. A retrobulbar block with lidocaine and triamcinolone settled residual oculodynia. At 1-year follow-up, the patient remained pain free and did not require analgesic medication. To our knowledge, this is the first reported case of ophthalmic division PHN successfully treated with a combination of trigeminal ganglion and retrobulbar nerve block using a local anesthetic agent and steroid for central and peripheral neural inflammatory processes. © 2016 World Institute of Pain.
On the Dynamics of Austral Heat Waves
NASA Astrophysics Data System (ADS)
Risbey, James S.; O'Kane, Terence J.; Monselesan, Didier P.; Franzke, Christian L. E.; Horenko, Illia
2018-01-01
This work examines summer heat wave events in four different regions of Australia (southwest, central, southeast, and northeast) to assess similarities and differences in the circulations that precede, accompany, and follow the heat wave events. A series of circulation composites are constructed for days from 10 days prior to 5 days following onset of each heat wave event. The composites of geopotential height anomalies and wave activity flux vectors show that heat waves in southwest and southeast Australia are preceded by coherent wave train structures in the Indian Ocean region, accompanied by blocking in the Australian region (as an amplified node of the wave train structure), and followed by coherent responses of wave train patterns in the Pacific and South America regions. The heat wave blocking high is maintained by convergence of wave activity in a well-defined wave channel. The concentration of wave activity in the block is aided by the formation of a subtropical jet branch and wave barrier on the equatorward side of the block. Heat waves in central and northeast Australia show similar wave train life cycle responses, but with a proximate ridge in the midtroposphere and a trough in the nearby waveguide region. Heat waves in Australia can be viewed as an element of successive expression of the planetary waveguide modes in the Southern Hemisphere and serve as signifiers of organized, active phases of these modes.
Late Jurassic low latitude of Central Iran: paleogeographic and tectonic implications
NASA Astrophysics Data System (ADS)
Mattei, Massimo; Muttoni, Giovanni; Cifelli, Francesca
2014-05-01
The individual blocks forming present-day Central Iran are now comprised between the Zagros Neo-Tethys suture to the south and the Alborz Palaeo-Tethys suture to the north. At the end of the Palaeozoic, the Iranian blocks rifted away from the northern margin of Gondwana as consequence of the opening of the Neo-Tethys, and collided with Eurasia during the Late Triassic, giving place to the Eo-Cimmerian orogeny. From then on, the Iranian block(s) should have maintained European affinity. Modern generations of apparent polar wander paths (APWPs) show the occurrence in North American and African coordinates of a major and rapid shift in pole position (=plate shift) during the Middle-Late Jurassic. This so-called monster polar shift is predicted also for Eurasia from the North Atlantic plate circuit, but Jurassic data from this continent are scanty and problematic. Here, we present paleomagnetic data from the Kimmeridgian-Tithonian (Upper Jurassic) Garedu Formation of Iran. Paleomagnetic component directions of primary (pre-folding) age indicate a paleolatitude of deposition of 10°N ± 5° that is in excellent agreement with the latitude drop predicted for Iran from APWPs incorporating the Jurassic monster polar shift. We show that paleolatitudes calculated from these APWPs, used in conjunction with simple zonal climate belts, better explain the overall stratigraphic evolution of Iran during the Mesozoic.
Fineberg, Jeffrey D.; Szanto, Tibor G.; Panyi, Gyorgy; Covarrubias, Manuel
2016-01-01
Voltage-gated K+ (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate. PMID:27502553
Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance.
Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben
2015-12-01
Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca(2+)-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia.
Effects of Chitin and Contact Insecticide Complexes on Rove Beetles in Commercial Orchards
Balog, A.; Ferencz, L.; Hartel, T.
2011-01-01
A five-year research project was performed to explore the potential effects of contact insecticide applications on the change of abundance and species richness of predatory rove beetles (Coleoptera: Staphylinidae) in conventionally managed orchards. Twelve blocks of nine orchards were used for this study in Central Europe. High sensitivity atomic force microscopic examination was carried out for chitin structure analyses as well as computer simulation for steric energy calculation between insecticides and chitin. The species richness of rove beetles in orchards was relatively high after insecticide application. Comparing the mean abundance before and after insecticide application, a higher value was observed before spraying with alphacypermethrin and lambda-cyhalothrin, and a lower value was observed in the cases of diflubenzuron, malathion, lufenuron, and phosalone. The species richness was higher only before chlorpyrifos-methyl application. There was a negative correlation between abundance and stability value of chitin-insecticides, persistence time, and soil absorption coefficients. Positive correlation was observed with lipo- and water solubility. PMID:21870981
Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao; Li, Zhisong; Wu, Shaogen; Sun, Linlin; Atianjoh, Fidelis E.; Feng, Jian; Mo, Kai; Jia, Shushan; Lutz, Brianna Marie; Bekker, Alex; Nestler, Eric J.; Tao, Yuan-Xiang
2017-01-01
Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG. PMID:28270689
Nuclear reactor removable radial shielding assembly having a self-bowing feature
Pennell, William E.; Kalinowski, Joseph E.; Waldby, Robert N.; Rylatt, John A.; Swenson, Daniel V.
1978-01-01
A removable radial shielding assembly for use in the periphery of the core of a liquid-metal-cooled fast-breeder reactor, for closing interassembly gaps in the reactor core assembly load plane prior to reactor criticality and power operation to prevent positive reactivity insertion. The assembly has a lower nozzle portion for inserting into the core support and a flexible heat-sensitive bimetallic central spine surrounded by blocks of shielding material. At refueling temperature and below the spine is relaxed and in a vertical position so that the tolerances permitted by the interassembly gaps allow removal and replacement of the various reactor core assemblies. During an increase in reactor temperature from refueling to hot standby, the bimetallic spine expands, bowing the assembly toward the core center line, exerting a radially inward gap-closing-force on the above core load plane of the reactor core assembly, closing load plane interassembly gaps throughout the core prior to startup and preventing positive reactivity insertion.
Comparison of solar-thermal and fossil total-energy systems for selected industrial applications
NASA Astrophysics Data System (ADS)
Pine, G. D.
1980-06-01
Economic analyses of a conventional system and total energy systems based on phosphoric acid fuel cells, diesel piston engines, and central receiver solar thermal systems were performed for each of four industrial applications; a concrete block plant in Arizona, a fluid milk processing plant in California, a sugar beet processing plant in Colorado, and a meat packing plant in Texas. A series of sensitivity analyses was performed to show the effects of variations in fuel price, system size, cost of capital, and system initial cost. Solar total energy systems (STES) are more capital intensive than the other systems, and significant economies of scale are associated with the STES. If DOE solar system cost goals are met, STES can compete with the other systems for facilities with electrical demands greater than two or three megawatts, but STES are not competitive for smaller facilities. Significant energy resource savings, especially of oil and gas, resulted from STES implementation in the four industries.
Biophysics of object segmentation in a collision-detecting neuron
Dewell, Richard Burkett
2018-01-01
Collision avoidance is critical for survival, including in humans, and many species possess visual neurons exquisitely sensitive to objects approaching on a collision course. Here, we demonstrate that a collision-detecting neuron can detect the spatial coherence of a simulated impending object, thereby carrying out a computation akin to object segmentation critical for proper escape behavior. At the cellular level, object segmentation relies on a precise selection of the spatiotemporal pattern of synaptic inputs by dendritic membrane potential-activated channels. One channel type linked to dendritic computations in many neural systems, the hyperpolarization-activated cation channel, HCN, plays a central role in this computation. Pharmacological block of HCN channels abolishes the neuron's spatial selectivity and impairs the generation of visually guided escape behaviors, making it directly relevant to survival. Additionally, our results suggest that the interaction of HCN and inactivating K+ channels within active dendrites produces neuronal and behavioral object specificity by discriminating between complex spatiotemporal synaptic activation patterns. PMID:29667927
Aguila, Maria-Eliza R; Rebbeck, Trudy; Leaver, Andrew M; Lagopoulos, Jim; Brennan, Patrick C; Hübscher, Markus; Refshauge, Kathryn M
2016-10-01
Migraine is prevalent and disabling yet is poorly understood. One way to better understand migraine is to examine its clinical characteristics and potential biomarkers such as gamma-aminobutyric acid (GABA). The primary objective of this study was to explore whether relevant disease characteristics of migraine are associated with brain GABA levels. Twenty adults fulfilling the established diagnostic criteria for migraine and 20 age- and gender-matched controls completed this cross-sectional study. Pain, central sensitization, negative emotional state, and perceived disability were measured using Short-form McGill Pain Questionnaire-2, Central Sensitization Inventory, Depression Anxiety Stress Scales-21, and Headache Impact Test-6, respectively. Secondary analysis of brain GABA levels of the same cohort measured using proton magnetic resonance spectroscopy was conducted. The migraine group had significantly higher scores than the control group on pain, central sensitization, and disability. Correlation analyses showed fair positive association between GABA levels and pain and central sensitization scores. No association was found between GABA levels and emotional state and disability. These findings are preliminary evidence supporting the use of questionnaires and GABA levels in characterizing migraine better and broadening the diagnostic process. These findings also strengthen the rationale for the role of GABA in migraine pathophysiology and corroborate the potential of GABA as a migraine biomarker. Higher pain and central sensitization scores were associated with increased brain GABA levels in individuals with migraine. These findings offer preliminary evidence for the usefulness of measuring pain and central sensitization in migraine and provide some support for the possible role of GABA in migraine pathophysiology and its potential as a diagnostic marker. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Schobelock, J.; Stamps, D. S.; Pagani, M.; Garcia, J.; Styron, R. H.
2017-12-01
The Caribbean and Central America region (CCAR) undergoes the entire spectrum of earthquake types due to its complex tectonic setting comprised of transform zones, young oceanic spreading ridges, and subductions along its eastern and western boundaries. CCAR is, therefore, an ideal setting in which to study the impacts of long-term tectonic deformation on the distribution of present-day seismic activity. In this work, we develop a continuous tectonic strain rate model based on inter-seismic geodetic data and compare it with known active faults and earthquake focal mechanism data. We first create a 0.25o x 0.25o finite element mesh that is comprised of block geometries defined in previously studies. Second, we isolate and remove transient signals from the latest open access community velocity solution from UNAVCO, which includes 339 velocities from COCONet and TLALOCNet GNSS data for the Caribbean and Central America, respectively. In a third step we define zones of deformation and rigidity by creating a buffer around the boundary of each block that varies depending on the size of the block and the expected deformation zone based on locations of GNSS data that are consistent with rigid block motion. We then assign each node within the buffer a 0 for the deforming areas and a plate index outside the buffer for the rigid. Finally, we calculate a tectonic strain rate model for CCAR using the Haines and Holt finite element approach to fit bi-cubic Bessel splines to the the GNSS/GPS data assuming block rotation for zones of rigidity. Our model of the CCAR is consistent with compression along subduction zones, extension across the mid-Pacific Rise, and a combination of compression and extension across the North America - Caribbean plate boundary. The majority of CCAR strain rate magnitudes range from -60 to 60 nanostrains/yr. Modeling results are then used to calculate expected faulting behaviors that we compare with mapped geologic faults and seismic activity.
Taylor M. Wilcox; Michael K. Schwartz; Kevin S. McKelvey; Michael K. Young; Winsor H. Lowe
2014-01-01
Environmental DNA (eDNA) is increasingly applied as a highly sensitive way to detect aquatic animals non-invasively. However, distinguishing closely related taxa can be particularly challenging. Previous studies of ancient DNA and genetic diet analysis have used blocking primers to enrich target template in the presence of abundant, non-target DNA. Here we apply a...
Soil-contact decay tests using small blocks : a procedural analysis
Rodney C. De Groot; James W. Evans; Paul G. Forsyth; Camille M. Freitag; Jeffrey J. Morrell
Much discussion has been held regarding the merits of laboratory decay tests compared with field tests to evaluate wood preservatives. In this study, procedural aspects of soil jar decay tests with 1 cm 3 blocks were critically examined. Differences among individual bottles were a major source of variation in this method. The reproducibility and sensitivity of the soil...
C. T. Scott; R. Hernandez; C. Frihart; R. Gleisner; T. Tice
2005-01-01
A new method for quantifying percentage wood failure of an adhesively bonded block-shear specimen has been developed. This method incorporates a laser displacement gage with an automated two-axis positioning system that functions as a highly sensitive profilometer. The failed specimen is continuously scanned across its width to obtain a surface failure profile. The...
pH-Dependent, Thermosensitive Polymeric Nanocarriers for Drug Delivery to Solid Tumors
Chen, Ching-Yi; Kim, Tae Hee; Wu, Wen-Chung; Huang, Chi-Ming; Wei, Hua; Mount, Christopher W.; Tian, Yanqing; Jang, Sei-Hum; Pun, Suzie H.; Jen, Alex K-Y
2013-01-01
Polymeric micelles are promising carriers for anticancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice. PMID:23498892
Optical study of solar tower power plants
NASA Astrophysics Data System (ADS)
Eddhibi, F.; Ben Amara, M.; Balghouthi, M.; Guizani, A.
2015-04-01
The central receiver technology for electricity generation consists of concentrating solar radiation coming from the solar tracker field into a central receiver surface located on the top of the tower. The heliostat field is constituted of a big number of reflective mirrors; each heliostat tracks the sun individually and reflects the sunlight to a focal point. Therefore, the heliostat should be positioned with high precision in order to minimize optical losses. In the current work, a mathematical model for the analysis of the optical efficiency of solar tower field power plant is proposed. The impact of the different factors which influence the optical efficiency is analyzed. These parameters are mainly, the shading and blocking losses, the cosine effect, the atmospheric attenuation and the spillage losses. A new method for the calculation of blocking and shadowing efficiency is introduced and validated by open literature.
Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor
2012-04-11
Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Villegas-Pineda, Julio César, E-mail: jcvillegas@cinvestav.mx; Toledo-Leyva, Alfredo, E-mail: toledo_leyva@hotmail.com; Osorio-Trujillo, Juan Carlos, E-mail: clostrujillo2@yahoo.com.mx
Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survivalmore » of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.« less
Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.
Ogilvie, R I; Zborowska-Sluis, D
1990-03-01
The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.
Sharma, Anshul; Mori, Taizo; Mahnen, Cory J; Everson, Heather R; Leslie, Michelle T; Nielsen, Alek D; Lussier, Laurent; Zhu, Chenhui; Malcuit, Christopher; Hegmann, Torsten; McDonough, Jennifer A; Freeman, Ernest J; Korley, LaShanda T J; Clements, Robert J; Hegmann, Elda
2017-02-01
The authors report on series of side-chain smectic liquid crystal elastomer (LCE) cell scaffolds based on star block-copolymers featuring 3-arm, 4-arm, and 6-arm central nodes. A particular focus of these studies is placed on the mechanical properties of these LCEs and their impact on cell response. The introduction of diverse central nodes allows to alter and custom-modify the mechanical properties of LCE scaffolds to values on the same order of magnitude of various tissues of interest. In addition, it is continued to vary the position of the LC pendant group. The central node and the position of cholesterol pendants in the backbone of ε-CL blocks (alpha and gamma series) affect the mechanical properties as well as cell proliferation and particularly cell alignment. Cell directionality tests are presented demonstrating that several LCE scaffolds show cell attachment, proliferation, narrow orientational dispersion of cells, and highly anisotropic cell growth on the as-synthesized LCE materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Astrophysics Data System (ADS)
Azaïez, Hajer; Bédir, Mourad; Tanfous, Dorra; Soussi, Mohamed
2007-05-01
In central Tunisia, Lower Cretaceous deposits represent carbonate and sandstone reservoir series that correspond to proven oil fields. The main problems for hydrocarbon exploration of these levels are their basin tectonic configuration and their sequence distribution in addition to the source rock availability. The Central Atlas of Tunisia is characterized by deep seated faults directed northeast-southwest, northwest-southeast and north-south. These faults limit inherited tectonic blocks and show intruded Triassic salt domes. Lower Cretaceous series outcropping in the region along the anticline flanks present platform deposits. The seismic interpretation has followed the Exxon methodologies in the 26th A.A.P.G. Memoir. The defined Lower Cretaceous seismic units were calibrated with petroleum well data and tied to stratigraphic sequences established by outcrop studies. This allows the subsurface identification of subsiding zones and thus sequence deposit distribution. Seismic mapping of these units boundary shows a structuring from a platform to basin blocks zones and helps to understand the hydrocarbon reservoir systems-tract and horizon distribution around these domains.
Sherwood, John L; Amici, Mascia; Dargan, Sheila L; Culley, Georgia R; Fitzjohn, Stephen M; Jane, David E; Collingridge, Graham L; Lodge, David; Bortolotto, Zuner A
2012-09-01
Long-term potentiation (LTP) is a well-established experimental model used to investigate the synaptic basis of learning and memory. LTP at mossy fibre - CA3 synapses in the hippocampus is unusual because it is normally N-methyl-d-aspartate (NMDA) receptor-independent. Instead it seems that the trigger for mossy fibre LTP involves kainate receptors (KARs). Although it is generally accepted that pre-synaptic KARs play an essential role in frequency facilitation and LTP, their subunit composition remains a matter of significant controversy. We have reported previously that both frequency facilitation and LTP can be blocked by selective antagonism of GluK1 (formerly GluR5/Glu(K5))-containing KARs, but other groups have failed to reproduce this effect. Moreover, data from receptor knockout and mRNA expression studies argue against a major role of GluK1, supporting a more central role for GluK2 (formerly GluR6/Glu(K6)). A potential reason underlying the controversy in the pharmacological experiments may reside in differences in the preparations used. Here we show differences in pharmacological sensitivity of synaptic plasticity at mossy fibre - CA3 synapses depend critically on slice orientation. In transverse slices, LTP of fEPSPs was invariably resistant to GluK1-selective antagonists whereas in parasagittal slices LTP was consistently blocked by GluK1-selective antagonists. In addition, there were pronounced differences in the magnitude of frequency facilitation and the sensitivity to the mGlu2/3 receptor agonist DCG-IV. Using anterograde labelling of granule cells we show that slices of both orientations possess intact mossy fibres and both large and small presynaptic boutons. Transverse slices have denser fibre tracts but a smaller proportion of giant mossy fibre boutons. These results further demonstrate a considerable heterogeneity in the functional properties of the mossy fibre projection. Copyright © 2012 Elsevier Ltd. All rights reserved.
Performance Evaluation and Initial Clinical Test of the Positron Emission Mammography System (PEMi)
NASA Astrophysics Data System (ADS)
Li, Lin; Gu, Xiao-Yue; Li, Dao-Wu; Huang, Xian-Chao; Chai, Pei; Feng, Bao-Tong; Wang, Pei-Lin; Yun, Ming-Kai; Dai, Dong; Zhang, Zhi-Ming; Yin, Peng-Fei; Xu, Wen-Gui; Wei, Long
2015-10-01
A new polygon positron emission mammography imaging system (PEMi) was developed in 2009 by the Institute of High Energy Physics, Chinese Academy of Sciences. PEMi is constructed in a polygon structure with lutetium yttrium orthosilicate crystal arrays mounted on a position-sensitive photomultiplier. The system consists of 64 blocks and each block is arranged in 16 ×16 crystal arrays with a pixel size of 1.9 ×1.9 ×15 mm. The diameter of the detector ring is 166 mm, and the axial length is 128 mm. The transaxial field of view of PEMi is 110 mm. The goal of the initial study was to test PEMi's performance and the clinical imaging ability with a small group of selected subjects. The detectors have a measured intrinsic spatial resolution averaging 1.67 mm. The axial and tangential resolution remained under 2.5-mm full width at half maximum within the central 5-cm diameter of the field of view. The hot rods with a diameter of 1.7 mm can be clearly identified, and the structure of the region containing 1.35-mm diameter rods can also be observed. Using a 6-ns coincidence timing window and a 360 660-keV energy window, the peak sensitivity of the tomograph is 6.88%. The noise-equivalent count rate peak is 110 766 cps for a breast-like cylindrical phantom of 100 mm in diameter at an activity concentration of 0.03 MBq/cc. The recovery coefficients ranged from 0.21 to 0.85 for rods between 1 mm and 5 mm in the image-quality phantom. The reconstructed image resolution achieved an improvement compared with whole-body positron emission tomography (PET), which might reduce the lower threshold on detectable lesion size. Example patient images demonstrate that PEMi is clinically feasible. And more detailed structure information was obtained with PEMi than with the whole-body PET imaging.
Sciatica: Detection and Confirmation by New Method
Nadkarni, Sunil
2014-01-01
We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--“mechanosensitized,” as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further. Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG. Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the nerve and relieve pain moment we desensitize the nerve. PMID:25694916
Selective blockade of microRNA processing by Lin-28
Viswanathan, Srinivas R.; Daley, George Q.; Gregory, Richard I.
2012-01-01
MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked post-transcriptionally in embryonic stem (ES) cells, embryonal carcinoma (EC) cells, and primary tumors. Here we show that Lin-28, a developmentally regulated RNA-binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we demonstrate that Lin-28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin-28 as a negative regulator of miRNA biogenesis and suggest that Lin-28 may play a central role in blocking miRNA-mediated differentiation in stem cells and certain cancers. PMID:18292307
Lee-Lewandrowski, Elizabeth; Januzzi, James L; Grisson, Ricky; Mohammed, Asim A; Lewandrowski, Grant; Lewandrowski, Kent
2011-04-01
Previous studies evaluating point-of-care testing (POCT) for cardiac biomarkers did not use current recommendations for troponin cutoff values or recognize the recent universal definition of acute myocardial infarction. Traditionally, achieving optimal sensitivity for the detection of myocardial injury on initial presentation required combining cardiac troponin and/or creatine kinase isoenzyme MB with an early marker, usually myoglobin. In recent years, the performance of central laboratory combining cardiac troponin assays has improved significantly, potentially obviating the need for a multimarker panel to achieve optimum sensitivity. To compare 2 commonly used POCT strategies to a fourth generation, central laboratory cardiac troponin T assay on first-draw specimens from patients being evaluated for acute myocardial infarction in the emergency department. The 2 strategies included a traditional POCT multimarker panel and a newer POCT method using cardiac troponin I alone. Blood specimens from 204 patients presenting to the emergency department with signs and/or symptoms of myocardial ischemia were measured on the 2 POCT systems and by a central laboratory method. The diagnosis for each patient was determined by retrospective chart review. The cardiac troponin T assasy alone was more sensitive for acute myocardial infarction than the multimarker POCT panel with equal or better specificity. When compared with a POCT troponin I, the cardiac troponin T was also more sensitive, but this difference was not significant. The POCT troponin I alone also had the same sensitivity as the multimarker panel. Testing for combining cardiac troponin alone using newer, commercially available, central laboratory or POCT assays performed with equal or greater sensitivity to acute myocardial infarction as the older, traditional, multimarker panel. In the near future, high-sensitivity, central laboratory troponins will be available for routine clinical use. As a result, the quality gap between central laboratories and older POCT methods will continue to widen, unless the performance of the POCT methods is improved.
Goutier, Wouter; Kloeze, Margreet B; McCreary, Andrew C
2015-03-01
The present study focused on the evaluation of behavioral sensitization and cross-sensitization induced by nicotine and varenicline in rats. Furthermore, it examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist, on nicotine-induced sensitization. To assess the development of behavioral sensitization, rats were chronically treated with vehicle, varenicline (0.03-3.0 mg/kg), nicotine (0.4 mg/kg) or combinations for 5 days and locomotor activity was measured. The expression of sensitization was assessed following a withdrawal period (17-26 days). The present results confirmed previous data showing the development and expression of nicotine-induced sensitization of locomotor activity in the rat. Varenicline did not induce sensitization on its own. When varenicline and nicotine were repeatedly administered sequentially, varenicline blocked the development and expression of nicotine-induced sensitization. Acute varenicline blocked the expression of nicotine-induced sensitization in a dose-dependent manner. Acute varenicline did not significantly increase locomotor activity, nor did it attenuate nicotine-induced sensitization. However, varenicline did cross-sensitize to the effects of nicotine, and vice versa. The present study showed that varenicline produced a dose-dependent bidirectional cross-sensitization with nicotine. Taken together, these findings provide pre-clinical evidence that varenicline is able to attenuate the effects of nicotine, yet simultaneously 'substitutes' for the effects of nicotine in the rat. Longitudinal studies would be needed to see if similar effects are seen in the clinical setting, and whether such effects contribute to the actions of varenicline as a smoking cessation aid. © 2013 Society for the Study of Addiction.
[Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].
Iniushkin, A N; Merkulova, N A; Orlova, A O; Iniushkina, E M
2009-07-01
In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.
2011-01-01
Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids). PMID:21542893
NASA Astrophysics Data System (ADS)
Stastnik, S.
2016-06-01
Development of materials for vertical outer building structures tends to application of hollow clay blocks filled with some appropriate insulation material. Ceramic fittings provide high thermal resistance, but the walls built from them suffer from condensation of air humidity in winter season frequently. The paper presents the computational simulation and experimental laboratory validation of moisture behaviour of such masonry with insulation prepared from waste fibres under the Central European climatic conditions.
[Experience with combined spinal and epidural anesthesia at cesarean section].
Levinzon, A S; Taran, O I; Pura, K R; Mishchenko, G S; Mamaeva, N V
2006-01-01
The paper analyzes some experience gained in using various modes of regional anesthesia as an anesthetic appliance at cesarean sections and comparatively characterizes various types of central segmental blocks. The results of 213 cases of cesarean section performed under spinal or combined spinal and epidural anesthesia (CSEA) were generalized by the following parameters: block onset, maternal and fetal action, the quality of anesthesia and postoperative analgesia, which leads to the conclusion that CSEA is the method of choice.
Agulleiro, Jose-Ignacio; Fernandez, Jose-Jesus
2015-01-01
Cache blocking is a technique widely used in scientific computing to minimize the exchange of information with main memory by reusing the data kept in cache memory. In tomographic reconstruction on standard computers using vector instructions, cache blocking turns out to be central to optimize performance. To this end, sinograms of the tilt-series and slices of the volumes to be reconstructed have to be divided into small blocks that fit into the different levels of cache memory. The code is then reorganized so as to operate with a block as much as possible before proceeding with another one. This data article is related to the research article titled Tomo3D 2.0 – Exploitation of Advanced Vector eXtensions (AVX) for 3D reconstruction (Agulleiro and Fernandez, 2015) [1]. Here we present data of a thorough study of the performance of tomographic reconstruction by varying cache block sizes, which allows derivation of expressions for their automatic quasi-optimal tuning. PMID:26217710
Agulleiro, Jose-Ignacio; Fernandez, Jose-Jesus
2015-06-01
Cache blocking is a technique widely used in scientific computing to minimize the exchange of information with main memory by reusing the data kept in cache memory. In tomographic reconstruction on standard computers using vector instructions, cache blocking turns out to be central to optimize performance. To this end, sinograms of the tilt-series and slices of the volumes to be reconstructed have to be divided into small blocks that fit into the different levels of cache memory. The code is then reorganized so as to operate with a block as much as possible before proceeding with another one. This data article is related to the research article titled Tomo3D 2.0 - Exploitation of Advanced Vector eXtensions (AVX) for 3D reconstruction (Agulleiro and Fernandez, 2015) [1]. Here we present data of a thorough study of the performance of tomographic reconstruction by varying cache block sizes, which allows derivation of expressions for their automatic quasi-optimal tuning.
Characterizing permanent magnet blocks with Helmholtz coils
NASA Astrophysics Data System (ADS)
Carnegie, D. W.; Timpf, J.
1992-08-01
Most of the insertion devices to be installed at the Advanced Photon Source will utilize permanent magnets in their magnetic structures. The quality of the spectral output is sensitive to the errors in the field of the device which are related to variations in the magnetic properties of the individual blocks. The Advanced Photon Source will have a measurement facility to map the field in the completed insertion devices and equipment to test and modify the magnetic strength of the individual magnet blocks. One component of the facility, the Helmholtz coil permanent magnet block measurement system, has been assembled and tested. This system measures the total magnetic moment vector of a block with a precision better than 0.01% and a directional resolution of about 0.05°. The design and performance of the system will be presented.
Let there be light: photo-cross-linked block copolymer nanoparticles.
Roy, Debashish; Sumerlin, Brent S
2014-01-01
Polymeric nanoparticles are prepared by selectively cross-linking a photo-sensitive dimethylmaleimide-containing block of a diblock copolymer via UV irradiation. A well-defined photo-cross-linkable block copolymer is prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization of a dimethylmaleimide-functional acrylamido monomer containing photoreactive pendant groups with a poly(N,N-dimethylacrylamide) (PDMA) macro-chain transfer agent. The resulting amphiphilic block copolymers form micelles in water with a hydrophilic PDMA shell and a hydrophobic photo-cross-linkable dimethylmaleimide-containing core. UV irradiation results in photodimerization of the dimethylmaleimide groups within the micelle cores to yield core-cross-linked aggregates. Alternatively, UV irradiation of homogeneous solutions of the block copolymer in a non-selective solvent leads to in situ nanoparticle formation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.
Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok; Jun, Jae Yeoul
2014-08-01
Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.
Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon
Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok
2014-01-01
Lubiprostone is a chloride (Cl-) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K+] channel blocker) and apamin (a calcium [Ca2+]-dependent K+ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K+ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K+ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K+ channel through a prostanoid EP receptor-independent mechanism. PMID:25177167
Inhibition of the cardiac inward rectifier potassium currents by KB-R7943.
Abramochkin, Denis V; Alekseeva, Eugenia I; Vornanen, Matti
2013-09-01
KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea) was developed as a specific inhibitor of the sarcolemmal sodium-calcium exchanger (NCX) with potential experimental and therapeutic use. However, KB-R7943 is shown to be a potent blocker of several ion currents including inward and delayed rectifier K(+) currents of cardiomyocytes. To further characterize KB-R7943 as a blocker of the cardiac inward rectifiers we compared KB-R7943 sensitivity of the background inward rectifier (IK1) and the carbacholine-induced inward rectifier (IKACh) currents in mammalian (Rattus norvegicus; rat) and fish (Carassius carassius; crucian carp) cardiac myocytes. The basal IK1 of ventricular myocytes was blocked with apparent IC50-values of 4.6×10(-6) M and 3.5×10(-6) M for rat and fish, respectively. IKACh was almost an order of magnitude more sensitive to KB-R7943 than IK1 with IC50-values of 6.2×10(-7) M for rat and 2.5×10(-7) M for fish. The fish cardiac NCX current was half-maximally blocked at the concentration of 1.9-3×10(-6) M in both forward and reversed mode of operation. Thus, the sensitivity of three cardiac currents to KB-R7943 block increases in the order IK1~INCX
Staud, Roland; Weyl, Elizabeth E.; Riley, Joseph L.; Fillingim, Roger B.
2014-01-01
Background In healthy individuals slow temporal summation of pain or wind-up (WU) can be evoked by repetitive heat-pulses at frequencies of ≥.33 Hz. Previous WU studies have used various stimulus frequencies and intensities to characterize central sensitization of human subjects including fibromyalgia (FM) patients. However, many trials demonstrated considerable WU-variability including zero WU or even wind-down (WD) at stimulus intensities sufficient for activating C-nociceptors. Additionally, few WU-protocols have controlled for contributions of individual pain sensitivity to WU-magnitude, which is critical for WU-comparisons. We hypothesized that integration of 3 different WU-trains into a single WU-response function (WU-RF) would not only control for individuals’ pain sensitivity but also better characterize their central pain responding including WU and WD. Methods 33 normal controls (NC) and 38 FM patients participated in a study of heat-WU. We systematically varied stimulus intensities of.4 Hz heat-pulse trains applied to the hands. Pain summation was calculated as difference scores of 1st and 5th heat-pulse ratings. WU-difference (WU-Δ) scores related to 3 heat-pulse trains (44°C, 46°C, 48°C) were integrated into WU-response functions whose slopes were used to assess group differences in central pain sensitivity. WU-aftersensations (WU-AS) at 15 s and 30 s were used to predict clinical FM pain intensity. Results WU-Δ scores linearly accelerated with increasing stimulus intensity (p<.001) in both groups of subjects (FM>NC) from WD to WU. Slope of WU-RF, which is representative of central pain sensitivity, was significantly steeper in FM patients than NC (p<.003). WU-AS predicted clinical FM pain intensity (Pearson’s r = .4; p<.04). Conclusions Compared to single WU series, WU-RFs integrate individuals’ pain sensitivity as well as WU and WD. Slope of WU-RFs was significantly different between FM patients and NC. Therefore WU-RF may be useful for assessing central sensitization of chronic pain patients in research and clinical practice. PMID:24558475
Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature
Walitt, Brian; Čeko, Marta; Gracely, John L.; Gracely, Richard H.
2016-01-01
Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging “signature” cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of “central sensitivity syndromes” is based more soundly on clinical and epidemiological evidence. A coherent picture of a “central sensitization” mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence. PMID:26717948
C. A. Clausen; S. N. Kartal
2003-01-01
Early detection of wood decay is critical because decay fungi can cause rapid structural failure. The objective of this study was to compare the sensitivity of different methods purported to detect brown-rot decay in the early stages of development. The immunodiagnostic wood decay (IWD)test, soil block test/cake pan test, mechanical property tests, and chemical...
Infants Use Social Context to Bind Actions into a Collaborative Sequence
ERIC Educational Resources Information Center
Fawcett, Christine; Gredebäck, Gustaf
2013-01-01
Eye tracking was used to show that 18-month-old infants are sensitive to social context as a sign that others' actions are bound together as a collaborative sequence based on a joint goal. Infants observed five identical demonstrations in which Actor 1 moved a block to one location and Actor 2 moved the same block to a new location, creating…
ZnS/Al2S3 Layer as a Blocking Layer in Quantum Dot Sensitized Solar Cells
NASA Astrophysics Data System (ADS)
Vafapoor, Borzoo; Fathi, Davood; Eskandari, Mehdi
2017-12-01
In this research, the effect of treatment of the CdS/CdSe sensitized ZnO photoanode by ZnS, Al2S3, and ZnS/Al2S3 nanoparticles as a barrier layer on the performance of quantum dot sensitized solar cell is investigated. Current density-voltage (J-V) characteristics show that cell efficiency is enhanced from 3.62% to 4.82% with treatment of a CdS/CdSe/ZnS sensitized ZnO photoanode by Al2S3 nanoparticles. In addition, short- circuit current density (J sc) is increased from 11.5 mA/cm2 to 14.8 mA/cm2. The results extracted from electrochemical impedance spectroscopy indicate that charge transfer resistance (R ct) in photoanode/electrolyte interfaces decreases with deposition of Al2S3 nanoparticles on CdS/CdSe/ZnS sensitized ZnO photoanodes, while the chemical capacitance of photoanode (C μ ) and electron lifetime (t n) increase. Also, results revealed that cell performance is considerably decreased with the treatment of the AL2S3 blocking layer incorporated between ZnO nanorods and CdS/CdSe QDs.
ZnS/Al2S3 Layer as a Blocking Layer in Quantum Dot Sensitized Solar Cells
NASA Astrophysics Data System (ADS)
Vafapoor, Borzoo; Fathi, Davood; Eskandari, Mehdi
2018-03-01
In this research, the effect of treatment of the CdS/CdSe sensitized ZnO photoanode by ZnS, Al2S3, and ZnS/Al2S3 nanoparticles as a barrier layer on the performance of quantum dot sensitized solar cell is investigated. Current density-voltage ( J- V) characteristics show that cell efficiency is enhanced from 3.62% to 4.82% with treatment of a CdS/CdSe/ZnS sensitized ZnO photoanode by Al2S3 nanoparticles. In addition, short- circuit current density ( J sc) is increased from 11.5 mA/cm2 to 14.8 mA/cm2. The results extracted from electrochemical impedance spectroscopy indicate that charge transfer resistance ( R ct) in photoanode/electrolyte interfaces decreases with deposition of Al2S3 nanoparticles on CdS/CdSe/ZnS sensitized ZnO photoanodes, while the chemical capacitance of photoanode ( C μ ) and electron lifetime ( t n) increase. Also, results revealed that cell performance is considerably decreased with the treatment of the AL2S3 blocking layer incorporated between ZnO nanorods and CdS/CdSe QDs.
Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.
Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A
2010-01-27
Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.
Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia
Garami, Andras; Shimansky, Yury P.; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Romanovsky, Andrej A.
2010-01-01
Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We have found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia. PMID:20107070
Basement structure based on gravity anomaly in the northern Noto peninsula, Central Japan
NASA Astrophysics Data System (ADS)
Mizubayashi, T.; Sawada, A.; Hamada, M.; Hiramatsu, Y.; Honda, R.
2012-12-01
Upper crustal block structures are usually defined by using surface information, such as geological and morphological data. The northern Noto Peninsula, central Japan, is divided into four geological block structures from tectonic geomorphologic perspectives (Ota and Hirakawa, 1979). This division is based on the surface crustal movement. To image the geological blocks three-dimensionally, it is necessary to construct a subsurface structure model. Gravity survey can clarify the detailed subsurface structure with dense gravity measurement. From the detailed Bouguer anomalies in the northwestern Noto Peninsula, Honda et al. (2008) suggested that the rupture size of the 2007 Noto Hanto earthquake was constrained by the geological block structures. Hiramatsu et al. (2008) also suggested the active faults on the seafloor, such as the source fault of the 2007 Noto Hanto earthquake plays a major role for the formation of the geological block structures. In this study, we analyze subsurface density structure based on the Bouguer anomaly and estimate the distribution of basement depth in the northern Noto Peninsula. We focus the relationship among the basement depth, the block structures and the active faults on the seafloor and discuss the block movement in the northern Noto Peninsula. We compiled the data measured and published previously (Gravity Database of Southwest Japan, 2001; Geological survey of Japan, 2004; Geographical survey institute of Japan, 2006; The Gravity Research Group in Southwest Japan, 2001; Komazawa and Okuma, 2010; Hokuriku electric power Co. Ltd., undisclosed) and calculated Bouguer anomaly in the northern Noto Peninsula. Based on this Bouguer anomaly, we analyzed subsurface density structures along 13 northeastern-southwestern profiles and 35 northwestern-southeastern profiles with the interval of 2 km using the two dimensional Talwani's method (Talwani et al., 1959). In the analysis, we assumed a density structure with four layers: basement (density is 2670kg/m3), Neocene volcanic rock (density is 2400kg/m3, or 2550kg/m3), Neocene sedimentary rock (density is 2200kg/m3), and Quaternary sedimentary rock (density is 1800kg/m3, or 1500kg/m3) (Honda et al., 2008). To compare our basement model to the geological block structures, we focus on a transition zone of the basement depth. We recognize that two of three geological block boundaries correspond to the transition zones. These boundaries also correspond to the boundary of active fault segments on the seafloor. Therefore, based on the relationship between the source fault of the 2007 Noto Hanto earthquake and the geological block, we suggest that the movement of those geological blocks is possibly controlled by the corresponding active fault segments. However, we find that the other block boundary doesn't correspond to the transition zone.
NASA Astrophysics Data System (ADS)
Zhou, Jian-Bo; Wilde, Simon A.; Zhang, Xing-Zhou; Liu, Fu-Lai; Liu, Jian-Hui
2012-03-01
Rocks that crop out in the northern part of the Songliao Block are mainly consist of high-grade metamorphic gneiss, Paleozoic strata and Mesozoic granites. They are essentially similar to rocks reported from beneath the Songliao Basin that occupies the majority of the Songliao Block. Four samples of Paleozoic metasedimentary rocks from Tieli in the north-eastern part of the Songliao Block yield detrital zircon U-Pb ages ranging from 2690 to 501 Ma, with four age populations at: 2071-2690 Ma, with a peak at 2585 Ma; 1776-1997 Ma, with a peak at 1890 Ma; 719-991 Ma, with a peak at 800 Ma; and 501-592 Ma, with a peak at 518 Ma. These are similar to age populations in other parts of the Central Asian Orogenic Belt (CAOB), although sediments from the Songliao Block contain more abundant Archean and Proterozoic detrital zircons than the neighboring Jiamusi-Khanka Block to the east and Xing'an Block to the west. This may indicate that rocks of this age comprise a minor component of the Songliao Block. The Pan-African zircon ages from the Songliao Block, taken together with ˜500 Ma magmatic and high-grade metamorphic zircons obtained from the nearby Erguna, Xing'an and Jiamusi-Khanka blocks, indicate that Pan-African events affected all blocks of the CAOB in NE China. This suggests that these blocks not only share a common basement, but that they had a common history. An extensive Late Pan-African (˜500 Ma) orogenic terrane thus occupies much of the CAOB in NE China.
NASA Astrophysics Data System (ADS)
Babault, Julien; Viaplana-Muzas, Marc; Legrand, Xavier; Van Den Driessche, Jean; González-Quijano, Manuel; Mudd, Simon M.
2018-05-01
The island of New Guinea is the result of continent-arc collision that began building the island's Central Range during the late Miocene. Recent studies have shown that rapid subduction, uplift and exhumation events took place in response to rapid, oblique convergence between the Pacific and the Australian plates. The tectonic and sedimentary evolution of Cenderawasih Bay, in the northwestern part of the New Guinea Island is still poorly understood: this bay links a major structural block, the Kepala Burung block, to the island's Central Ranges. Previous studies have shown that Cenderawasih Bay contains a thick (>8 km) sequence of undated sediments. One hypothesis claims that the embayment resulted from a 3 Ma opening created by anticlockwise rotation of the Kepala Burung block with respect to the northern rim of the Australian plate. Alternatively, the current configuration of Cenderawasih Bay could have resulted from the southwest drift of a slice of volcanics and oceanic crust between 8 and 6 Ma. We test these hypotheses using (i) a geomorphologic analysis of the drainage network dynamics, (ii) a reassessment of available thermochronological data, and (iii) seismic lines interpretation. We suggest that sediments started to accumulate in Cenderawasih Bay and onshore in the Waipoga Basin in the late Miocene since the inception of growth of the Central Range, beginning at 12 Ma, resulting in sediment accumulation of up to 12,200 m. This evidence is more consistent with the second hypothesis, and the volume of sediment accumulated means it is unlikely that the embayment was the result of recent (2-3 Ma) rotation of structural blocks. At first order, we predict that infilling is mainly composed of siliciclastics sourced in the graphite-bearing Ruffaer Metamorphic Belt and its equivalent in the Weyland Overthrust. Ophiolites, volcanic arc rocks and diorites contribute minor proportions. From the unroofing paths in the Central Range we deduce two rates of solid phase accumulation (SPAR) since 12 Ma, the first one at a mean SPAR ranging between 0.12 and 0.25 mm/a with a maximum SPAR of 0.23-0.58 mm/a, and the second during the last 3 Ma, at a mean SPAR ranging between 0.93 and 1.62 mm/a and with a maximum SPAR between 2.13 and 3.17 mm/a, i.e., 6700-10,000 m of Plio-Pleistocene sediment accumulation. Local transtensional tectonics may explain these unusually high rates of sedimentation in an overall sinistral oblique convergence setting.
Pryor, G T; Rebert, C S
1992-01-01
Solvent mixtures are ubiquitous in industrialized environments and are used frequently for recreational purposes. Toluene and hexane are common components of many solvent mixtures and have characteristic, but different, neurotoxic consequences. Interestingly, Takeuchi et al., (1981) reported that toluene attenuated the peripheral neuropathy caused by n-hexane, possibly by blocking its metabolism to 2,5-hexanedione (Perbellini, et al., 1982). To confirm such effects at higher concentrations and to examine effects on the central nervous system (CNS), four groups of 12 rats each were exposed to air, toluene (1200 ppm), hexane (4000 ppm), or a mixture of toluene (1200 ppm) and hexane (4,000 ppm) 14 hr/day for 9 weeks. A battery of behavioral and electrophysiologic tests was used to assess the functional consequences of their exposures. The battery consisted of measures of grip strength, locomotor gait and landing splay, sensory sensitivities during conditioned avoidance performance, the action potential of the ventral caudal nerve, and the brainstem auditory evoked response. Measures of peripheral nervous system functions (e.g., grip strength and conduction velocity) showed interactive effects like those reported by Takeuchi et al. Toluene greatly reduced the neuropathy caused by hexane. Hexane-induced abnormalities in central components of the brainstem response were much less reduced in the presence of toluene. There was no reciprocal action of hexane on the motor syndrome and hearing loss caused by toluene.
Endocannabinoid antagonism: blocking the excess in the treatment of high-risk abdominal obesity.
Duffy, Danielle; Rader, Daniel
2007-02-01
Abdominal obesity is a prevalent, worldwide problem linked to cardiometabolic comorbidities and an increased risk of coronary heart disease. First-line therapy to reduce such risk revolves around diet and exercise; however, such changes are often difficult to implement and unsuccessful. Understanding the underlying pathophysiology of underlying metabolic derangements could provide new targets for pharmacologic therapy. One system that has gained recent attention is the endocannabinoid system. The endocannabinoid system has a significant role in central appetite control and peripheral lipogenesis and is up-regulated in diet-induced obesity. Rimonabant is a selective cannabinoid-1 receptor antagonist and is the first compound of its type to test the hypothesis that down-regulating an overactive endocannabinoid system could have therapeutic benefit not only for weight loss but also for the atherogenic dyslipidemia and insulin resistance that cluster with abdominal obesity in particular. Animal models have been critical for elucidating the role of the endocannabinoid system in obesity and in demonstrating that antagonism with rimonabant can induce loss of visceral fat and improve insulin sensitivity. Early human trials with rimonabant have confirmed significant reductions in weight, as well as favorable changes in atherogenic dyslipidemia, insulin resistance, and markers of inflammation. Interestingly, some of these beneficial metabolic effects are partially weight-loss-independent, confirming the importance of peripheral endocannabinoid system effects in addition to central effects.
Hellman, Dana; Sakuma, Ryu; Shandas, Vivek
2018-01-01
Extreme urban heat is a powerful environmental stressor which poses a significant threat to human health and well-being. Exacerbated by the urban heat island phenomenon, heat events are expected to become more intense and frequent as climate change progresses, though we have limited understanding of the impact of such events on vulnerable populations at a neighborhood or census block group level. Focusing on the City of Portland, Oregon, this study aimed to determine which socio-demographic populations experience disproportionate exposure to extreme heat, as well as the level of access to refuge in the form of public cooling centers or residential central air conditioning. During a 2014 heat wave, temperature data were recorded using a vehicle-traverse collection method, then extrapolated to determine average temperature at the census block group level. Socio-demographic factors including income, race, education, age, and English speaking ability were tested using statistical assessments to identify significant relationships with heat exposure and access to refuge from extreme heat. Results indicate that groups with limited adaptive capacity, including those in poverty and non-white populations, are at higher risk for heat exposure, suggesting an emerging concern of environmental justice as it relates to climate change. The paper concludes by emphasizing the importance of cultural sensitivity and inclusion, in combination with effectively distributing cooling centers in areas where the greatest burden befalls vulnerable populations. PMID:29601546
Voelkel, Jackson; Hellman, Dana; Sakuma, Ryu; Shandas, Vivek
2018-03-30
Extreme urban heat is a powerful environmental stressor which poses a significant threat to human health and well-being. Exacerbated by the urban heat island phenomenon, heat events are expected to become more intense and frequent as climate change progresses, though we have limited understanding of the impact of such events on vulnerable populations at a neighborhood or census block group level. Focusing on the City of Portland, Oregon, this study aimed to determine which socio-demographic populations experience disproportionate exposure to extreme heat, as well as the level of access to refuge in the form of public cooling centers or residential central air conditioning. During a 2014 heat wave, temperature data were recorded using a vehicle-traverse collection method, then extrapolated to determine average temperature at the census block group level. Socio-demographic factors including income, race, education, age, and English speaking ability were tested using statistical assessments to identify significant relationships with heat exposure and access to refuge from extreme heat. Results indicate that groups with limited adaptive capacity, including those in poverty and non-white populations, are at higher risk for heat exposure, suggesting an emerging concern of environmental justice as it relates to climate change. The paper concludes by emphasizing the importance of cultural sensitivity and inclusion, in combination with effectively distributing cooling centers in areas where the greatest burden befalls vulnerable populations.
NASA Astrophysics Data System (ADS)
Gürsoy, H.; Tatar, O.; Piper, J. D. A.; Koçbulut, F.; Akpınar, Zafer; Huang, Baochun; Roberts, A. P.; Mesci, B. L.
2011-05-01
The Anatolian accretionary collage between Afro-Arabia and Eurasia is currently subject to two tectonic regimes. Ongoing slip of Arabia relative to Africa along the Dead Sea Fault Zone in the east is extruding crustal blocks away from the indenter by a combination of strike-slip and rotation. This zone of compression gives way to an extensional province in western Turkey, which also includes the eastern sector of Aegean Province. Although it is now well established that rotational deformation throughout Anatolia is distributed and differential, the sizes of the blocks involved are poorly understood. As a contribution towards evaluating this issue in central-east Turkey, we report palaeomagnetic study of the mid-Miocene Kepezdağ and Yamadağ volcanic complexes in central-south Anatolia (38-39.5°N, 37.5-39°E). A distributed sample through the Yamadağ complex identifies eruption during an interval of multiple geomagnetic field reversals (40 normal, 36 reversed, 8 intermediate sites) with a selected mean defined by 63 sites of D/ I = 335.4/51.1° ( α95 = 4.4°). The smaller Kepezdağ complex (8 reversed, 4 normal and 1 intermediate site) yields a comparable mean direction from 12 sites of 338.7/49.8° ( α95 = 14.1°). In the context of a range of radiometric age evidence, two thick normal polarity zones within the Yamadağ succession probably correlate with zones C5ACn and C5ADn of the Geomagnetic Polarity Time Scale and imply that the bulk of the volcanic activity took place between ˜15 and 13.5 Ma. Comparison of the palaeomagnetic results with the adjoining major plate indenters shows that the Yamadağ complex has rotated CCW by 29.3 ± 5.2° relative to Eurasia; the much smaller dataset from the Kepezdağ complex indicates a comparable CCW rotation of 26.0 ± 11.8° with respect to Eurasia. The Arabian Indenter has also been rotating CCW since mid Miocene times, and the block incorporating these two volcanic complexes north of the East Anatolian Fault Zone (EAFZ) is determined to have rotated 18.2 ± 6.0° CCW relative to the northern perimeter of Arabia. Comparison with data to the north identifies quasi-uniform rotation across a ˜200 km wide block extending from the Central Anatolian Fault Zone in the northwest to close to the East Anatolian transform fault zone in the south east. Although absence of suitable younger rocks does not permit the timing of this rotation to be determined in the study area, analogies with results from the Sivas Basin suggest that it is young, and followed establishment of the major transform faults. Rotation has evidently taken place around bounding arcuate faults and accompanied westward expulsion as the accretionary collage north of Arabia has been subject to ongoing post-collisional indentation.
Relevance of Conduction Disorders in Bachmann's Bundle During Sinus Rhythm in Humans.
Teuwen, Christophe P; Yaksh, Ameeta; Lanters, Eva A H; Kik, Charles; van der Does, Lisette J M E; Knops, Paul; Taverne, Yannick J H J; van de Woestijne, Pieter C; Oei, Frans B S; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S
2016-05-01
Bachmann's bundle (BB) is considered to be the main route of interatrial conduction and to play a role in development of atrial fibrillation (AF). The goals of this study are to characterize the presence of conduction disorders in BB during sinus rhythm and to study their relation with AF. High-resolution epicardial mapping (192 unipolar electrodes, interelectrode distance: 2 mm) of sinus rhythm was performed in 185 patients during coronary artery bypass surgery of whom 13 had a history of paroxysmal AF. Continuous rhythm monitoring was used to detect postoperative AF during the first 5 postoperative days. In 67% of the patients, BB was activated from right to left; in the remaining patients from right and middle (21%), right, central, and left (8%), or central (4%) site. Mean effective conduction velocity was 89 cm/s. Conduction block was present in most patients (75%; median 1.1%, range 0-12.8) and was higher in patients with paroxysmal AF compared with patients without a history of AF (3.2% versus 0.9%; P=0.03). A high amount of conduction block (>4%) was associated with de novo postoperative AF (P=0.02). Longitudinal lines of conduction block >10 mm were also associated with postoperative AF (P=0.04). BB may be activated through multiple directions, but the predominant route of conduction is from right to left. Conduction velocity across BB is around 90 cm/s. Conduction is blocked in both longitudinal and transverse direction in the majority of patients. Conduction disorders, particularly long lines of longitudinal conduction block, are more pronounced in patients with AF episodes. © 2016 American Heart Association, Inc.
The Hulan Group: Its role in the evolution of the Central Asian Orogenic Belt of NE China
NASA Astrophysics Data System (ADS)
Wu, Fu-Yuan; Zhao, Guo-Chun; Sun, De-You; Wilde, Simon A.; Yang, Jin-Hui
2007-05-01
The Hulan Group of central Jilin Province, northeastern (NE) China, consists of felsic volcanic and sedimentary rocks that underwent sub-greenschist to amphibolite facies metamorphism and multiple phases of deformation during formation of the Central Asian Orogenic Belt. Young Nd model ages of ˜1100 Ma obtained in this study do not support earlier models that the Hulan Group was either rifted from the North China Craton to the south or from the Jiamusi Block to the north, since both these blocks have much older Nd model ages. Detrital zircon U-Pb ages from a meta-sedimentary rock of the Hulan Group define a maximum age of deposition of 287 ± 6 Ma, not Early Palaeozoic as previously believed. Rb-Sr mineral isochron data indicate that metamorphism of the Hulan Group occurred at ˜250 Ma. This conclusion is further supported by an age of 248 ± 4 Ma for the Dayushan granite, which intruded the Hulan Group. These new isotopic data, together with evaluation of the regional geology, indicate that final oceanic closure in the Chinese segment of the Central Asian Orogenic Belt took place in the Late Permian. The Hulan area is located along the Solonker-Xra Moron-Changchun suture that extends from Inner Mongolia across to central Jilin Province. It is this zone that marks the final ocean closure, resulting in the amalgamation of the North China and Siberian cratons.
Shirayama, Yukihiko; Muneoka, Katsumasa; Fukumoto, Makoto; Tadokoro, Shigenori; Fukami, Goro; Hashimoto, Kenji; Iyo, Masaomi
2011-10-01
Patients with depression showed a decrease in plasma and cerebrospinal fluid allopregnanolone (ALLO). But antidepressants increased the contents of ALLO in the rat brain. We examined the antidepressant-like effects of infusion of ALLO into the cerebral ventricle, hippocampus, amygdala, nucleus accumbens, or prefrontal cortex of learned helplessness (LH) rats (an animal model of depression). Of these regions, infusions of ALLO into the cerebral ventricle, the CA3 region of hippocampus, or the central region of amygdala exerted antidepressant-like effects. Infusion of ALLO into the hippocampal CA3 region or the central amygdala did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. It is well documented that ALLO exerts its effects through GABA receptors. Therefore, we examined the antagonistic effects of flumazenil (a GABA receptor antagonist) on the antidepressant-like effects of ALLO. Coinfusion of flumazenil with ALLO into the hippocampal CA3 region, but not into the central amygdala, blocked the antidepressant-like effects of ALLO. However, coinfusion of (+)MK801 (an NMDA receptor antagonist), but not cycloheximide (a protein synthesis inhibitor), blocked the antidepressant-like effects of ALLO in the central amygdala. These results suggest that ALLO exerts antidepressant-like effects in the CA3 region of hippocampus through the GABA system and in the central region of amygdala, dependently on the activation of the glutamatergic mechanisms. Copyright © 2010 Wiley-Liss, Inc.
MATERNAL SENSITIVITY AND PERFORMANCE AND VERBAL INTELLIGENCE IN LATE CHILDHOOD AND ADOLESCENCE.
Dunkel, Curtis S; Woodley Of Menie, Michael A
2018-02-15
The aim of this study was to investigate the association between maternal sensitivity and offspring intelligence in late childhood and adolescence. Secondary data (N=117) from the Block and Block (2006a, b) 30-year longitudinal study of Californian children, which began in the late 1960s, was used to test the hypothesis that maternal sensitivity in childhood would be predictive of late childhood and adolescent intelligence. Correlational analyses revealed that maternal sensitivity, as judged by raters viewing mother's interactions with their children in a set of four joint structured cognitive tasks when the child was 5 years of age, was associated with verbal and performance IQ test scores when the children were ages 11 and 18. Using hierarchical regression to control for child sex, socioeconomic status, child temperament, child baseline IQ (as measured at age 4), mother's level of education and mother's emotional nurturance, it was found that the maternal sensitivity and child and adolescent IQ association held for verbal, but not performance IQ. Furthermore, a pattern emerged in which the association between maternal sensitivity and verbal IQ was stronger for adolescents with a lower baseline IQ. The results suggest that maternal sensitivity is associated with offspring verbal intelligence and that this association holds when numerous variables are accounted for. Additionally, this association may be stronger for children with lower IQs.
Alpha-conotoxin ImI Disrupts Central Control of Swimming in the Medicinal Leech
Wagenaar, Daniel A.; Gonzalez, Ruben; Ries, David C.; Kristan, William B.; French, Kathleen A.
2010-01-01
Medicinal leeches (Hirudo spp.) swim using a metachronal, front-to-back undulation. The behavior is generated by central pattern generators (CPGs) distributed along the animal’s midbody ganglia and is coordinated by both central and peripheral mechanisms. Here we report that a component of the venom of Conus imperialis, α-conotoxin ImI, known to block nicotinic acetylcholine receptors in other species, disrupts swimming. Leeches injected with the toxin swam in circles with exaggerated dorsoventral bends and reduced forward velocity. Fictive swimming in isolated nerve cords was even more strongly disrupted, indicating that the toxin targets the CPGs and central coordination, while peripheral coordination partially rescues the behavior in intact animals. PMID:20833225
1984-04-01
50] Collision Aeronaves - Boeing 747 PH-BUF de KLI y Boeing N737PA de Pan Amt en los rodeos (Tenerife) el 27 Marzo de 1977, Joint Accident Report...SAMPLE APPLICATION: FIRE-BLOCKING OF SEATS .......................... 24 4.1 Expected Losses and Savings with Seat Blocking ................... 26 4.2...analyzed to examine the sensitivity of the results on the existing materials. 24 MI ɚ C0 .04 4 0 Cc00 C 0 CU 4’.4 .. c o 90 .~w - -J 440 c 0 0 cq I04 C.0
Responsive Block Copolymer and Gold Nanoparticle Hybrid Nanotubes.
NASA Astrophysics Data System (ADS)
Chang, Sehoon; Singamaneni, Srikanth; Young, Seth; Tsukruk, Vladimir
2009-03-01
We demonstrate the facile fabrication of responsive polymer and metal nanoparticle composite nanotube structures. The nanotubes are comprised of responsive block copolymer, polystyrene-block-poly (2-vinylpyridine) (PS-b-P2VP), and gold nanoparticles. PS-b-P2VP nanotubes were fabricated using porous alumina template and in situ reduction of the gold nanoparticles in P2VP domains. Owing to the pH sensitive nature of P2VP (anionic polymer with a pKa of 3.8), the nanotubes exhibit a dramatic change in topology in response to the changes in the external pH. Furthermore, the gold nanoparticles in the responsive block exhibit a reversible aggregation, causing a reversible change in optical properties such as absorption.
Modeling Memory for Language Understanding.
1982-02-01
Abstract Research on natural language understanding by computer has shown that the nature and organization of memory plays j central role in the...block number) Research on natural language understanding by computer has shown that the nature and organization of memory plays a central role in the...understanding mechanism. Further we claim that such reminding is at the root of how we learn. Issues such as these have played an important part in shaping the
Xue, Qingwang; Liu, Chunxue; Li, Xia; Dai, Li; Wang, Huaisheng
2018-04-18
Various fluorescent sensing systems for miRNA detection have been developed, but they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrices. Here, we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive, and selective detection of miRNAs with low-background signal. In the strategy, a split G-quadruplex (3:1) sequence is ingeniously designed at both ends of two double-stranded DNAs, which is exploited as building blocks for nonlinear HCR assembly, thereby acquiring a low background signal. A hairpin switch probe (HSP) was employed as recognition and transduction element. Upon sensing the target miRNA, the nonlinear HCR assembly of two blocks (blocks-A and blocks-B) was initiated with the help of two single-stranded DNA assistants, resulting in chain-branching growth of DNA dendrimers with multiple G-quadruplex incorporation. With the zinc(II)-protoporphyrin IX (ZnPPIX) selectively intercalated into the multiple G-quadruplexes, fluorescent DNA dendrimers were obtained, leading to an exponential fluorescence intensity increase. Benefiting from excellent performances of nonlinear HCR and low background signal, this strategy possesses the characteristics of a simplified reaction operation process, as well as high sensitivity. Moreover, the proposed fluorescent sensing strategy also shows preferable selectivity, and can be implemented without modified DNA blocks. Importantly, the strategy has also been tested for miRNA quantification with high confidence in breast cancer cells. Thus, this proposed strategy for label-free fluorescent DNA dendrimers based on a nonlinear HCR-mediated multiple G-quadruplex will be turned into an alternative approach for simple, sensitive, and selective miRNA quantification.
Reliability of Waveform Analysis as an Adjunct to Loss of Resistance for Thoracic Epidural Blocks.
Leurcharusmee, Prangmalee; Arnuntasupakul, Vanlapa; Chora De La Garza, Daniel; Vijitpavan, Amorn; Ah-Kye, Sonia; Saelao, Abhidej; Tiyaprasertkul, Worakamol; Finlayson, Roderick J; Tran, De Q H
2015-01-01
The epidural space is most commonly identified with loss of resistance (LOR). Although sensitive, LOR lacks specificity, as cysts in interspinous ligaments, gaps in ligamentum flavum, paravertebral muscles, thoracic paravertebral spaces, and intermuscular planes can yield nonepidural LOR. Epidural waveform analysis (EWA) provides a simple confirmatory adjunct for LOR. When the needle is correctly positioned inside the epidural space, measurement of the pressure at its tip results in a pulsatile waveform. In this observational study, we set out to assess the sensitivity, specificity, as well as positive and negative predictive values of EWA for thoracic epidural blocks. We enrolled a convenience sample of 160 patients undergoing thoracic epidural blocks for thoracic surgery, abdominal surgery, or rib fractures. The choice of patient position (sitting or lateral decubitus), approach (midline or paramedian), and LOR medium (air or normal saline) was left to the operator (attending anesthesiologist, fellow, or resident). After obtaining a satisfactory LOR, the operator injected 5 mL of normal saline through the epidural needle. A sterile tubing, connected to a pressure transducer, was attached to the needle to measure the pressure at the needle tip. A 4-mL bolus of lidocaine 2% with epinephrine 5 μg/mL was then administered and, after 10 minutes, the patient was assessed for sensory blockade to ice. The failure rate (incorrect identification of the epidural space with LOR) was 23.1%. Of these 37 failed epidural blocks, 27 provided no sensory anesthesia at 10 minutes. In 10 subjects, the operator was unable to thread the catheter through the needle. When compared with the ice test, the sensitivity, specificity, and positive and negative predictive values of EWA were 91.1%, 83.8%, 94.9%, and 73.8%, respectively. Epidural waveform analysis (with pressure transduction through the needle) provides a simple adjunct to LOR for thoracic epidural blocks. Although its use was devoid of complications, further confirmatory studies are required before its routine implementation in clinical practice.
NASA Astrophysics Data System (ADS)
Taft, William C.; Delorenzo, Robert J.
1984-05-01
Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.
Taft, W C; DeLorenzo, R J
1984-01-01
Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance. PMID:6328498
NASA Astrophysics Data System (ADS)
Han, Sheng; Xi, Shi-qiong; Geng, Wei-dong
2017-11-01
In order to solve the problem of low recognition rate of traditional feature extraction operators under low-resolution images, a novel algorithm of expression recognition is proposed, named central oblique average center-symmetric local binary pattern (CS-LBP) with adaptive threshold (ATCS-LBP). Firstly, the features of face images can be extracted by the proposed operator after pretreatment. Secondly, the obtained feature image is divided into blocks. Thirdly, the histogram of each block is computed independently and all histograms can be connected serially to create a final feature vector. Finally, expression classification is achieved by using support vector machine (SVM) classifier. Experimental results on Japanese female facial expression (JAFFE) database show that the proposed algorithm can achieve a recognition rate of 81.9% when the resolution is as low as 16×16, which is much better than that of the traditional feature extraction operators.
NASA Astrophysics Data System (ADS)
Gorynski, Kyle E.; Stockli, Daniel F.; Douglas Walker, J.
2013-06-01
(AHe) and Zircon (ZHe) (U-Th)/He thermochronometric data from the southern Wassuk Range (WR) coupled with 40Ar/39Ar age data from the overlying tilted Tertiary section are used to constrain the thermal evolution of an extensional accommodation zone and tilt-domain boundary. AHe and ZHe data record two episodes of rapid cooling related to the tectonic exhumation of the WR fault block beginning at ~15 and ~4 Ma. Extension was accommodated through fault-block rotation and variably tilted the southern WR to the west from ~60°-70° in the central WR to ~15°-35° in the southernmost WR and Pine Grove Hills, and minimal tilting in the Anchorite Hills and along the Mina Deflection to the south. Middle Miocene geothermal gradient estimates record heating immediately prior to large-magnitude extension that was likely coeval with the extrusion of the Lincoln Flat andesite at ~14.8 Ma. Geothermal gradients increase from ~19° ± 4°C/km to ≥ 65° ± 20°C/km toward the Mina Deflection, suggesting that it was the focus of Middle Miocene arc magmatism in the upper crust. The decreasing thickness of tilt blocks toward the south resulted from a shallowing brittle/ductile transition zone. Postmagmatic Middle Miocene extension and fault-block advection were focused in the northern and central WR and coincidentally moderated the large lateral thermal gradient within the uppermost crust.
Blue-on-yellow perimetry to evaluate S cone sensitivity in diabetics.
Nomura, R; Terasaki, H; Hirose, H; Miyake, Y
2000-01-01
Blue-on-yellow (B/Y) perimetry was performed on 31 patients with non-insulin-dependent diabetes mellitus to study the loss of sensitivity to short wavelengths. Of these patients, 21 were without retinopathy (NDR) and 10 had early background retinopathy (SDR). Eleven normal subjects served as controls. The results were compared to white-on-white (W/W) perimetry. Foveal sensitivity determined by B/Y and W/W perimetry showed no significant difference between NDR, SDR and normals. However, the mean sensitivity in the central 30-degree area and that in the upper half of the central 20- to 30-degree concentric circular field were significantly decreased in B/Y perimetry in SDR patients (p < 0.05, p < 0.01, respectively). No significant sensitivity loss was detected in the W/W test. We conclude that there is a blue cone system sensitivity loss in the central 30-degree area, particularly in the upper half of the visual field and the paracentral area in diabetic patients with early background retinopathy. Copyright 2000 S. Karger AG, Basel
Downham, Christina; Broadbent, Ian; Charlton, Keith; Porter, Andrew J.
2014-01-01
A number of bacteria, including pathogens like Pseudomonas aeruginosa, utilize homoserine lactones (HSLs) as quorum sensing (QS) signaling compounds and engage in cell-to-cell communication to coordinate their behavior. Blocking this bacterial communication may be an attractive strategy for infection control as QS takes a central role in P. aeruginosa biology. In this study, immunomodulation of HSL molecules by monoclonal antibodies (MAbs) was used as a novel approach to prevent P. aeruginosa infections and as tools to detect HSLs in bodily fluids as a possible first clue to an undiagnosed Gram-negative infection. Using sheep immunization and recombinant antibody technology, a panel of sheep-mouse chimeric MAbs were generated which recognized HSL compounds with high sensitivity (nanomolar range) and cross-reactivity. These MAbs retained their nanomolar sensitivity in complex matrices and were able to recognize HSLs in P. aeruginosa cultures grown in the presence of urine. In a nematode slow-killing assay, HSL MAbs significantly increased the survival of worms fed on the antibiotic-resistant strain PA058. The therapeutic benefit of these MAbs was further studied using a mouse model of Pseudomonas infection in which groups of mice treated with HSL-2 and HSL-4 MAbs survived, 7 days after pathogen challenge, in significantly greater numbers (83 and 67%, respectively) compared with the control groups. This body of work has provided early proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as theranostic clinical leads suitable for the diagnosis, prevention, and treatment of life-threatening bacterial infections. PMID:24185854
NASA Astrophysics Data System (ADS)
Paíga, Paula; Silva, Luís M. S.; Delerue-Matos, Cristina
2016-10-01
The flow rates of drying and nebulizing gas, heat block and desolvation line temperatures and interface voltage are potential electrospray ionization parameters as they may enhance sensitivity of the mass spectrometer. The conditions that give higher sensitivity of 13 pharmaceuticals were explored. First, Plackett-Burman design was implemented to screen significant factors, and it was concluded that interface voltage and nebulizing gas flow were the only factors that influence the intensity signal for all pharmaceuticals. This fractionated factorial design was projected to set a full 22 factorial design with center points. The lack-of-fit test proved to be significant. Then, a central composite face-centered design was conducted. Finally, a stepwise multiple linear regression and subsequently an optimization problem solving were carried out. Two main drug clusters were found concerning the signal intensities of all runs of the augmented factorial design. p-Aminophenol, salicylic acid, and nimesulide constitute one cluster as a result of showing much higher sensitivity than the remaining drugs. The other cluster is more homogeneous with some sub-clusters comprising one pharmaceutical and its respective metabolite. It was observed that instrumental signal increased when both significant factors increased with maximum signal occurring when both codified factors are set at level +1. It was also found that, for most of the pharmaceuticals, interface voltage influences the intensity of the instrument more than the nebulizing gas flowrate. The only exceptions refer to nimesulide where the relative importance of the factors is reversed and still salicylic acid where both factors equally influence the instrumental signal.
Permutation testing of orthogonal factorial effects in a language-processing experiment using fMRI.
Suckling, John; Davis, Matthew H; Ooi, Cinly; Wink, Alle Meije; Fadili, Jalal; Salvador, Raymond; Welchew, David; Sendur, Levent; Maxim, Vochita; Bullmore, Edward T
2006-05-01
The block-paradigm of the Functional Image Analysis Contest (FIAC) dataset was analysed with the Brain Activation and Morphological Mapping software. Permutation methods in the wavelet domain were used for inference on cluster-based test statistics of orthogonal contrasts relevant to the factorial design of the study, namely: the average response across all active blocks, the main effect of speaker, the main effect of sentence, and the interaction between sentence and speaker. Extensive activation was seen with all these contrasts. In particular, different vs. same-speaker blocks produced elevated activation in bilateral regions of the superior temporal lobe and repetition suppression for linguistic materials (same vs. different-sentence blocks) in left inferior frontal regions. These are regions previously reported in the literature. Additional regions were detected in this study, perhaps due to the enhanced sensitivity of the methodology. Within-block sentence suppression was tested post-hoc by regression of an exponential decay model onto the extracted time series from the left inferior frontal gyrus, but no strong evidence of such an effect was found. The significance levels set for the activation maps are P-values at which we expect <1 false-positive cluster per image. Nominal type I error control was verified by empirical testing of a test statistic corresponding to a randomly ordered design matrix. The small size of the BOLD effect necessitates sensitive methods of detection of brain activation. Permutation methods permit the necessary flexibility to develop novel test statistics to meet this challenge.
Sudhagar, P; Asokan, K; Jung, June Hyuk; Lee, Yong-Gun; Park, Suil; Kang, Yong Soo
2011-12-01
A compact TiO2 layer (~1.1 μm) prepared by electrostatic spray deposition (ESD) and swift heavy ion beam (SHI) irradiation using oxygen ions onto a fluorinated tin oxide (FTO) conducting substrate showed enhancement of photovoltaic performance in dye-sensitized solar cells (DSSCs). The short circuit current density (Jsc = 12.2 mA cm(-2)) of DSSCs was found to increase significantly when an ESD technique was applied for fabrication of the TiO2 blocking layer, compared to a conventional spin-coated layer (Jsc = 8.9 mA cm(-2)). When SHI irradiation of oxygen ions of fluence 1 × 10(13) ions/cm(2) was carried out on the ESD TiO2, it was found that the energy conversion efficiency improved mainly due to the increase in open circuit voltage of DSSCs. This increased energy conversion efficiency seems to be associated with improved electronic energy transfer by increasing the densification of the blocking layer and improving the adhesion between the blocking layer and the FTO substrate. The adhesion results from instantaneous local melting of the TiO2 particles. An increase in the electron transport from the blocking layer may also retard the electron recombination process due to the oxidized species present in the electrolyte. These findings from novel treatments using ESD and SHI irradiation techniques may provide a new tool to improve the photovoltaic performance of DSSCs.
2011-01-01
A compact TiO2 layer (~1.1 μm) prepared by electrostatic spray deposition (ESD) and swift heavy ion beam (SHI) irradiation using oxygen ions onto a fluorinated tin oxide (FTO) conducting substrate showed enhancement of photovoltaic performance in dye-sensitized solar cells (DSSCs). The short circuit current density (Jsc = 12.2 mA cm-2) of DSSCs was found to increase significantly when an ESD technique was applied for fabrication of the TiO2 blocking layer, compared to a conventional spin-coated layer (Jsc = 8.9 mA cm-2). When SHI irradiation of oxygen ions of fluence 1 × 1013 ions/cm2 was carried out on the ESD TiO2, it was found that the energy conversion efficiency improved mainly due to the increase in open circuit voltage of DSSCs. This increased energy conversion efficiency seems to be associated with improved electronic energy transfer by increasing the densification of the blocking layer and improving the adhesion between the blocking layer and the FTO substrate. The adhesion results from instantaneous local melting of the TiO2 particles. An increase in the electron transport from the blocking layer may also retard the electron recombination process due to the oxidized species present in the electrolyte. These findings from novel treatments using ESD and SHI irradiation techniques may provide a new tool to improve the photovoltaic performance of DSSCs. PMID:27502653
Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.
Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U
2016-05-01
Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®
Block versus Random Amphiphilic Glycopolymer Nanopaticles as Glucose-Responsive Vehicles.
Guo, Qianqian; Zhang, Tianqi; An, Jinxia; Wu, Zhongming; Zhao, Yu; Dai, Xiaomei; Zhang, Xinge; Li, Chaoxing
2015-10-12
To explore the effect of polymer structure on their self-assembled aggregates and their unique characteristics, this study was devoted to developing a series of amphiphilic block and random phenylboronic acid-based glycopolymers by RAFT polymerization. The amphiphilic glycopolymers were successfully self-assembled into spherically shaped nanoparticles with narrow size distribution in aqueous solution. For block and random copolymers with similar monomer compositions, block copolymer nanoparticles exhibited a more regular transmittance change with the increasing glucose level, while a more evident variation of size and quicker decreasing tendency in I/I0 behavior in different glucose media were observed for random copolymer nanoparticles. Cell viability of all the polymer nanoparticles investigated by MTT assay was higher than 80%, indicating that both block and random copolymers had good cytocompatibility. Insulin could be encapsulated into both nanoparticles, and insulin release rate for random glycopolymer was slightly quicker than that for the block ones. We speculate that different chain conformations between block and random glycopolymers play an important role in self-assembled nanoaggregates and underlying glucose-sensitive behavior.
Differential reward coding in the subdivisions of the primate caudate during an oculomotor task.
Nakamura, Kae; Santos, Gustavo S; Matsuzaki, Ryuichi; Nakahara, Hiroyuki
2012-11-07
The basal ganglia play a pivotal role in reward-oriented behavior. The striatum, an input channel of the basal ganglia, is composed of subdivisions that are topographically connected with different cortical and subcortical areas. To test whether reward information is differentially processed in the different parts of the striatum, we compared reward-related neuronal activity along the dorsolateral-ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically rewarded oculomotor task. In a given block, a target in one position was associated with a large reward, whereas the other target was associated with a small reward. The target position-reward value contingency was switched between blocks. We found the following: (1) activity that reflected the block-wise reward contingency emerged before the appearance of a visual target, and it was more prevalent in the dorsal, rather than central and ventral, caudate; (2) activity that was positively related to the reward size of the current trial was evident, especially after reward delivery, and it was more prevalent in the ventral and central, rather than dorsal, caudate; and (3) activity that was modulated by the memory of the outcomes of the previous trials was evident in the dorsal and central caudate. This multiple reward information, together with the target-direction information, was represented primarily by individual caudate neurons, and the different reward information was represented in caudate subpopulations with distinct electrophysiological properties, e.g., baseline firing and spike width. These results suggest parallel processing of different reward information by the basal ganglia subdivisions defined by extrinsic connections and intrinsic properties.
NASA Astrophysics Data System (ADS)
Madonna, E.; Li, C.; Grams, C. M.; Woollings, T.
2017-12-01
Understanding the variability of the North Atlantic eddy-driven jet is key to unravelling the dynamics, predictability and climate change response of extratropical weather in the region. This study aims to 1) reconcile two perspectives on wintertime variability in the North Atlantic-European sector and 2) clarify their link to atmospheric blocking. Two common views of wintertime variability in the North Atlantic are the zonal-mean framework comprising three preferred locations of the eddy-driven jet (southern, central, northern), and the weather regime framework comprising four classical North Atlantic-European regimes (Atlantic ridge AR, zonal ZO, European/Scandinavian blocking BL, Greenland anticyclone GA). We use a k-means clustering algorithm to characterize the two-dimensional variability of the eddy-driven jet stream, defined by the lower tropospheric zonal wind in the ERA-Interim reanalysis. The first three clusters capture the central jet and northern jet, along with a new mixed jet configuration; a fourth cluster is needed to recover the southern jet. The mixed cluster represents a split or strongly tilted jet, neither of which is well described in the zonal-mean framework, and has a persistence of about one week, similar to the other clusters. Connections between the preferred jet locations and weather regimes are corroborated - southern to GA, central to ZO, and northern to AR. In addition, the new mixed cluster is found to be linked to European/Scandinavian blocking, whose relation to the eddy-driven jet was previously unclear. The results highlight the necessity of bridging from weather to climate scales for a deeper understanding of atmospheric circulation variability.
NASA Astrophysics Data System (ADS)
Jiang, M.; He, Y.; Zheng, T.; Mon, C. T.; Thant, M.; Hou, G.; Ai, Y.; Chen, Q. F.; Sein, K.
2017-12-01
The Indo-Myanmar block locates to the southern and southeastern of the Eastern Himalayan Syntax (EHS) and marks a torsional boundary of the collision between the Indian and Eurasian plates. There are two fundamental questions concerned on the tectonics of Indo-Myanmar block since the Cenozoic time. One is whether and how the oblique subduction is active in the deep; the other is where and how the transition from oceanic subduction and continental subduction operates. However, the two problems are still under heated debate mainly because the image of deep structure beneath this region is still blurring. Since June, 2016, we have executed the China-Myanmar Geophysical Survey in the Myanmar Orogen (CMGSMO) and deployed the first portable seismic array in Myanmar in cooperation with Myanmar Geosciences Society (MGS). This array contains 70 stations with a dense-deployed main profile across the Indo-Myanmar Range, Central Basin and Shan State Plateau along latitude of 22° and a 2-D network covering the Indo-Myanmar Range and the western part of the Central Basin. Based on the seismic data collected by the new array, we conducted the studies on the lithospheric structure using the routine surface wave tomography and receiver function CCP stacking. The preliminary results of surface wave tomography displayed a remarkable high seismic velocity fabric in the uppermost of mantle beneath the Indo-Myanmar Range and Central Basin, which was interpreted as the subducted slab eastward. Particularly, we found a low velocity bulk within the high-velocity slab, which was likely to be a slab window due to the slab tearing. The preliminary results of receiver function CCP stacking showed the obvious variations of the lithospheric structures from the Indo-Myanmar Range to the Central Basin and Shan State Plateau. The lithospheric structure beneath the Indo-Myanmar Range is more complex than that beneath the Central Basin and Shan State Plateau. Our resultant high-resolution images will provide important constrains for establishing the tectonic framework of Indian plate eastward subduction. This study is supported by the National Natural Science Foundation of China (grants 41490612, 41274002).
[Interest of ultrasonographic guidance in paediatric regional anaesthesia].
Dadure, C; Raux, O; Rochette, A; Capdevila, X
2009-10-01
The use of ultrasonographic guidance for regional anaesthesia has known recently a big interest in children in recent years. The linear ultrasound probes with a 25 mm active surface area (or probes with 38 mm active surface area in older children), with high sound frequencies in the range 8-14 MHz, allow a good compromise between excellent resolution for superficial structure and good penetration depths. In children, the easiest ultrasound guided blocks are axillar blocks, femoral blocks, fascia iliaca compartment blocks, ilio-inguinal blocks and para-umbilical blocks, caudal blocks. They permit a safe and easy learning curve of these techniques. The main advantage of ultrasound guided regional anaesthesia is the visualization of different anatomical structures and the approximate localization of the tip of needle. The other advantages for ultrasound guided peripheral nerve blocks in children are: faster onset time of sensory and motor block, longer duration of sensory blockade, increase of blockade quality and reduction of local anesthetic injection. The use of ultrasonographic guidance for central block allows to visualize different structures as well as spine and his content. Spinous process, ligament flavum, dura mater, conus medullaris and cerebrospinal fluid are identifiable, and give some information on spine, epidural space and the depth between epidural space and skin. At last, in caudal block, ultrasounds permit to evaluate the anatomy of caudal epidural space, especially the relation of the sacral hiatus to the dural sac and the search of occult spinal dysraphism. Benefit of this technique is the visualization of targeted nerves or spaces and the spread of injected local anaesthetic.
Impact of Atmospheric Blocking on South America in Austral Summer
NASA Astrophysics Data System (ADS)
Rodrigues, Regina; Woollings, Tim
2017-04-01
In this study, we investigate atmospheric blocking over east South America in austral summer for the period of 1979-2014. Our results show that blocking over this area is a consequence of propagating Rossby waves that grow to large amplitudes and eventually break anticyclonically over subtropical South America (SSA). The SSA blocking can prevent the establishment of the South Atlantic Convergence Zone (SACZ). As such, years with more blocking days coincide with years with fewer SACZ days and reduced precipitation. Convection mainly over the Indian Ocean associated with Madden-Julian Oscillation (MJO) phases 1 and 2 can trigger the wave train that leads to SSA blocking whereas convection over the western/central Pacific associated with phases 6 and 7 is more likely to lead to SACZ events. We find that MJO is a key source of long-term variability in SSA blocking frequency. The wave packets associated with SSA blocking and SACZ episodes differ not only in their origin but also in their phase and refraction pattern. The tropopause-based methodology used here is proven to reliably identify events that lead to extremes of surface temperature and precipitation over SSA. Up to 80% of warm surface air temperature extremes occur simultaneously with SSA blocking events. They are also responsible for the warming of western South Atlantic. The frequency of SSA blocking days is highly anti-correlated with the rainfall over southeast Brazil. The worst droughts in this area, during the summers of 1984, 2001 and 2014, are linked to record high numbers of SSA blocking days. The persistence of these events is also important in generating the extreme impacts.
Dry needling — peripheral and central considerations
Dommerholt, Jan
2011-01-01
Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects of central sensitization, it reduces local and referred pain, improves range of motion and muscle activation pattern, and alters the chemical environment of trigger points. Trigger point dry needling should be based on a thorough understanding of the scientific background of trigger points, the differences and similarities between active and latent trigger points, motor adaptation, and central sensitize application. Several outcome studies are included, as well as comments on dry needling and acupuncture. PMID:23115475
Dedkov, V S
2009-01-01
The specificity of DNA-methyltransferase M.Bsc4I was defined in cellular lysate of Bacillus schlegelii 4. For this purpose, we used methylation sensitivity of restriction endonucleases, and also modeling of methylation. The modeling consisted in editing sequences of DNA using replacements of methylated bases and their complementary bases. The substratum DNA processed by M.Bsc4I also were used for studying sensitivity of some restriction endonucleases to methylation. Thus, it was shown that M.Bsc4I methylated 5'-Cm4CNNNNNNNGG-3' and the overlapped dcm-methylation blocked its activity. The offered approach can appear universal enough and simple for definition of specificity of DNA-methyltransferases.
Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease
Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.
2016-01-01
Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469
NASA Astrophysics Data System (ADS)
Koulen, Peter; Gallimore, Gary; Vincent, Ryan D.; Sabates, Nelson R.; Sabates, Felix N.
2011-06-01
Conventional perimeters are used routinely in various eye disease states to evaluate the central visual field and to quantitatively map sensitivity. However, standard automated perimetry proves difficult for retina and specifically macular disease due to the need for central and steady fixation. Advances in instrumentation have led to microperimetry, which incorporates eye tracking for placement of macular sensitivity values onto an image of the macular fundus thus enabling a precise functional and anatomical mapping of the central visual field. Functional sensitivity of the retina can be compared with the observed structural parameters that are acquired with high-resolution spectral domain optical coherence tomography and by integration of scanning laser ophthalmoscope-driven imaging. Findings of the present study generate a basis for age-matched comparison of sensitivity values in patients with macular pathology. Microperimetry registered with detailed structural data performed before and after intervention treatments provides valuable information about macular function, disease progression and treatment success. This approach also allows for the detection of disease or treatment related changes in retinal sensitivity when visual acuity is not affected and can drive the decision making process in choosing different treatment regimens and guiding visual rehabilitation. This has immediate relevance for applications in central retinal vein occlusion, central serous choroidopathy, age-related macular degeneration, familial macular dystrophy and several other forms of retina related visual disability.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peryshkin, A. Yu., E-mail: alexb700@yandex.ru; Makarov, P. V., E-mail: bacardi@ispms.ru; Eremin, M. O., E-mail: bacardi@ispms.ru
An evolutionary approach proposed in [1, 2] combining the achievements of traditional macroscopic theory of solid mechanics and basic ideas of nonlinear dynamics is applied in a numerical simulation of present-day tectonic plates motion and seismic process in Central Asia. Relative values of strength parameters of rigid blocks with respect to the soft zones were characterized by the δ parameter that was varied in the numerical experiments within δ = 1.1–1.8 for different groups of the zonal-block divisibility. In general, the numerical simulations of tectonic block motion and accompanying seismic process in the model geomedium indicate that the numerical solutionsmore » of the solid mechanics equations characterize its deformation as a typical behavior of a nonlinear dynamic system under conditions of self-organized criticality.« less
Ancient ice islands in salt lakes of the Central Andes
Hurlbert, S.H.; Chang, Cecily C.Y.
1984-01-01
Massive blocks of freshwater ice and frozen sediments protrude from shallow, saline lakes in the Andes of southwestern Bolivia and northeastern Chile. These ice islands range up to 1.5 kilometers long, stand up to 7 meters above the water surface, and may extend out tens of meters and more beneath the unfrozen lake sediments. The upper surfaces of the islands are covered with dry white sediments, mostly aragonite or calcite. The ice blocks may have formed by freezing of the fresh pore water of lake sediments during the "little ice age." The largest blocks are melting rapidly because of possibly recent increases in geothermal heat flux through the lake bottom and undercutting by warm saline lake water during the summer.
NASA Astrophysics Data System (ADS)
Yin, J.; Chen, W.; Hodges, K. V.; Xiao, W.; Van Soest, M. C.; Cai, K.; Zhang, B.; Mercer, C. M.; Yuan, C.
2015-12-01
Geochronology and thermochronology using multiple mineral-isotopic chronometers reveals the thermo-tectonic history of the central Tianshan (NW China) from emplacement to exhumation. Granites from the central Tianshan, which are associated with the southward subduction of the northern Tianshan Ocean, have been dated at 362-354 Ma using the LA-ICP-MS Zircon U-Pb method. A younger diorite sample (282 ± 1 Ma, Zircon U-Pb method by LA-ICP-MS) from northern Tianshan formed during the final closure of the Northern Tianshan Ocean when the Junggar Block collided with the Yili-Central Tianshan Block. 40Ar/39Ar step-wise heating plateau dates (biotite Ar/Ar: 312-293 Ma; Plagioclase Ar/Ar: 270-229 Ma) from the Central Tianshan show rapid post-magmatic cooling during the Late Carboniferous-Early Permian followed by a more modest rate of cooling from the middle Permian to the middle Jurassic. The northern Tianshan diorite (biotite Ar/Ar: 240 ± 1 Ma) also reveals a middle Jurassic cooling. Apatite (U-Th )/He dates from the central Tianshan samples range from ca. 130 Ma to ca. 116 Ma. The Apatite (U-Th )/He date for the northern Tianshan sample is ca. 27 Ma. Previous studies also reported Apatite (U-Th)/He ages of ca. 44 Ma-11 Ma in the Baluntai area of the southern Central Tianshan[1]. Two episodes of cooling are distinguished by thermal history modelling: (1) Mesozoic cooling occurred as the result of the exhumation and tectonic reactivation of the central Tianshan; and (2) The Tianshan orogenic belt has been rapidly exhumed since the Middle Cenozoic. References [1] Lü, H.H., Chang, Y., Wang, W., Zhou, Z.Y., 2013. Rapid exhumation of the Tianshan Mountains since the early Miocene: Evidence from combined apatite fission track and (U-Th)/He thermochronology. Science China: Earth Sciences, 43(12): 1964-1974 (in Chinese).
Chen, Qianqian; Chen, Xiaoxiang; Zhang, Sichao; Lan, Ke; Lu, Jian; Zhang, Chiyu
2015-01-01
The development of simple, accurate, rapid and cost-effective technologies for mutation detection is crucial to the early diagnosis and prevention of numerous genetic diseases, pharmacogenetics, and drug resistance. Proofreading PCR (PR-PCR) was developed for mutation detection in 1998 but is rarely applied due to its low efficiency in allele discrimination. Here we developed a modified PR-PCR method using a ddNTP-blocked primer and a mixture of DNA polymerases with and without the 3'-5' proofreading function. The ddNTP-blocked primer exhibited the best blocking efficiency to avoid nonspecific primer extension while the mixture of a tiny amount of high-fidelity DNA polymerase with a routine amount of Taq DNA polymerase provided the best discrimination and amplification effects. The modified PR-PCR method is quite capable of detecting various mutation types, including point mutations and insertions/deletions (indels), and allows discrimination amplification when the mismatch is located within the last eight nucleotides from the 3'-end of the ddNTP-blocked primer. The modified PR-PCR has a sensitivity of 1-5 × 102 copies and a selectivity of 5 × 10-5 mutant among 107 copies of wild-type DNA. It showed a 100% accuracy rate in the detection of P72R germ-line mutation in the TP53 gene among 60 clinical blood samples, and a high potential to detect rifampin-resistant mutations at low frequency in Mycobacterium tuberculosis using an adaptor and a fusion-blocked primer. These results suggest that the modified PR-PCR technique is effective in detection of various mutations or polymorphisms as a simple, sensitive and promising approach. PMID:25915410
Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A
2017-08-01
Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Fan, Jilian; Yu, Linhui; Xu, Changcheng
2017-06-01
Triacylglycerol is a key intermediate in membrane lipid breakdown and fatty acid β-oxidation, and blocking triacylglycerol hydrolysis reduces oxidative stress and enhances plant survival under extended darkness.
Toxicologic Pathology: The Basic Building Block of Risk Assessment
Human health risk assessment is a critical factor in many risk management decisions. Evaluation of human health risk requires research the provides information that appropriately characterizes potential hazards from exposure. Pathology endpoints are the central response around ...
Gao, Yong-Jing; Ji, Ru-Rong
2009-01-01
c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization. PMID:19898681
NASA Astrophysics Data System (ADS)
Wilmsen, Markus; Storm, Marisa; Fürsich, Franz Theodor; Majidifard, Mahmoud Reza
2013-12-01
Wilmsen, M., Storm, M., Fürsich, F.T. and Majidifard, M.R. 2013. Upper Albian and Cenomanian (Cretaceous) ammonites from the Debarsu Formation (Yazd Block, Central Iran). Acta Geologica Polonica, 63 (4), 489-513. Warszawa. New ammonite faunas consisting of 13 taxa provide the first reliable biostratigraphic dating of the Debarsu Formation of the Yazd Block, west-central Iran, indicating several levels in the Upper Albian and Lower Cenomanian, while a foraminiferal assemblage places the top of the Formation in the Middle Turonian. Among the identified ammonite taxa, Acompsoceras renevieri (Sharpe, 1857) is recorded from Iran for the first time. The upper part of the lower Upper Albian is proved by the occurrences of mortoniceratines of the Mortoniceras (M.) inflatum Zone in the lowermost part of the Debarsu Formation. For the upper Upper Albian (traditional Stoliczkaia dispar Zone), the M. (Subschloenbachia ) rostratum and M. (S.) perinflatum zones are proved by their index taxa. However, there is no evidence of the terminal Arrhaphoceras (Praeschloenbachia) briacensis Zone. The upper part of the lower Lower Cenomanian Mantelliceras mantelli Zone (M. saxbii Subzone) is proved by M. saxbii and M. cf. mantelli. Below, there is an ammonite- barren interval of ca. 100 m in thickness between M. (S.) perinflatum zonal strata and the M. saxbii Subzone. The upper Lower Cenomanian is documented by the presence of typically M. dixoni zonal ammonites such as Acompsoceras renevieri. Upper Cenomanian and Turonian ammonites have not been found in the upper part of the Debarsu Formation, but micro-biostratigraphic evidence (planktonic foraminifers) from the uppermost part of the formation indicate that the formation ranges into the Turonian. For the development of the major tectonic unconformity at the base of the overlying Haftoman Formation (which yielded Lower Coniacian inoceramids near its base), only 2-3 myr remain, stressing the geodynamic activity of Central Iran during mid-Cretaceous times.
Atmospheric Radiation Measurement Program facilities newsletter, July 2000.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sisterson, D. L.; Holdridge, D. J., ed.
2000-08-03
For improved safety in and around the ARM SGP CART site, the ARM Program recently purchased and installed an aircraft detection radar system at the central facility near Lamont, Oklahoma. The new system will enhance safety measures already in place at the central facility. The SGP CART site, especially the central facility, houses several instruments employing laser technology. These instruments are designed to be eye-safe and are not a hazard to personnel at the site or pilots of low-flying aircraft over the site. However, some of the specialized equipment brought to the central facility by visiting scientists during scheduled intensivemore » observation periods (IOPs) might use higher-power laser beams that point skyward to make measurements of clouds or aerosols in the atmosphere. If these beams were to strike the eye of a person in an aircraft flying above the instrument, damage to the person's eyesight could result. During IOPs, CART site personnel have obtained Federal Aviation Administration (FAA) approval to temporarily close the airspace directly over the central facility and keep aircraft from flying into the path of the instrument's laser beam. Information about the blocked airspace is easily transmitted to commercial aircraft, but that does not guarantee that the airspace remains completely plane-free. For this reason, during IOPs in which non-eye-safe lasers were in use in the past, ARM technicians watched for low-flying aircraft in and around the airspace over the central facility. If the technicians spotted such an aircraft, they would manually trigger a safety shutter to block the laser beam's path skyward until the plane had cleared the area.« less
The Role of Neuropeptides in Persistent Virus Infections of the Central Nervous System
1990-05-10
5000 61153N RR04108 441f722 11. TITLE (include Security Classification) (U) The role of neuropeptides in persistent virus infections of the central...identify by block number) FIELD GROUP SUB-GROUP opioids, lymphocytes, infections , nervous system, virus, immunity, neuropeptides 19 ABSTRACT (Continue on...endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, re- sulted in 74% survival; and 39% of the
Color variations within glacial till, east-central North Dakota--A preliminary investigation
Kelly, T.E.; Baker, Claud H.
1966-01-01
Color variations (orange zones within buff-colored till) in drift in east-central North Dakota are believed to represent two tills of separate origin. Mean size, standard deviation, and number and type of pebbles show greater difference between the two tills than do skewness, kurtosis, and partial chemical analyses. Probably blocks of older till were moved by the last glacier crossing the area and were redeposited in a matrix of younger till.
Angulo, M C; Parra, P; Dieudonné, S
1998-03-01
Voltage-gated calcium channels form a complex family of distinct molecular entities which participate in multiple neuronal functions. In cerebellar Purkinje cells these channels contribute to the characteristic electrophysiological pattern of complex spikes, first described in birds and later in mammals. A specific calcium channel, the P-type channel, has been shown to mediate the majority of the voltage-gated calcium flux in mammalian Purkinje cells. P-type channels play an essential role in synaptic transmission of mammalian cerebellum. It is unclear whether the P-type calcium channel is present in birds. Studies in chick synaptosomal preparations show that the pharmacological profile of calcium channels is complex and suggest a minimal expression of the P-type channel in avian central nervous system. In the present work, we studied voltage-gated calcium channels in dissociated chick cerebellar Purkinje cells to examine the presence of different calcium channel types. Purkinje cells were used because, in mammals, they express predominantly P-type channels and because the morphology of these cells is thought to be phylogenetically conserved. We found that omega-conotoxin GVIA (omega-CgTx GVIA), a specific antagonist of N-type calcium channel, rather than the synthetic funnel-web spider toxin (sFTX), a P-type channel antagonist, blocks the majority of the barium current flowing through calcium channels in chick Purkinje neurons.
Lexical Retrieval is not by Competition: Evidence from the Blocked Naming Paradigm
Navarrete, Eduardo; Del Prato, Paul; Peressotti, Francesca; Mahon, Bradford Z.
2014-01-01
A central issue in research on speech production is whether or not the retrieval of words from the mental lexicon is a competitive process. An important experimental paradigm to study the dynamics of lexical retrieval is the blocked naming paradigm, in which participants name pictures of objects that are grouped by semantic category (‘homogenous’ or ‘related’ blocks) or not grouped by semantic category (‘heterogeneous’ or ‘unrelated’ blocks). Typically, pictures are repeated multiple times (or cycles) within both related and unrelated blocks. It is known that participants are slower in related than in unrelated blocks when the data are collapsed over all within-block repetitions. This semantic interference effect, as observed in the blocked naming task, is the strongest empirical evidence for the hypothesis of lexical selection by competition. Here we show, contrary to the accepted view, that the default polarity of semantic context effects in the blocked naming paradigm is facilitation, rather than interference. In a series of experiments we find that interference arises only when items repeat within a block, and only because of that repetition: What looks to be ‘semantic interference’ in the blocked naming paradigm is actually less repetition priming in related compared to unrelated blocks. These data undermine the theory of lexical selection by competition and indicate a model in which the most highly activated word is retrieved, regardless of the activation levels of nontarget words. We conclude that the theory of lexical selection by competition, and by extension the important psycholinguistic models based on that assumption, are no longer viable, and frame a new way to approach the question of how words are retrieved in spoken language production. PMID:25284954
Chasing the Garlock: A study of tectonic response to vertical axis rotation
NASA Astrophysics Data System (ADS)
Guest, Bernard; Pavlis, Terry L.; Golding, Heather; Serpa, Laura
2003-06-01
Vertical-axis, clockwise block rotations in the Northeast Mojave block are well documented by numerous authors. However, the effects of these rotations on the crust to the north of the Northeast Mojave block have remained unexplored. In this paper we present a model that results from mapping and geochronology conducted in the north and central Owlshead Mountains. The model suggests that some or all of the transtension and rotation observed in the Owlshead Mountains results from tectonic response to a combination of clockwise block rotation in the Northeast Mojave block and Basin and Range extension. The Owlshead Mountains are effectively an accommodation zone that buffers differential extension between the Northeast Mojave block and the Basin and Range. In addition, our model explores the complex interactions that occur between faults and fault blocks at the junction of the Garlock, Brown Mountain, and Owl Lake faults. We hypothesize that the bending of the Garlock fault by rotation of the Northeast Mojave block resulted in a misorientation of the Garlock that forced the Owl Lake fault to break in order to accommodate slip on the western Garlock fault. Subsequent sinistral slip on the Owl Lake fault offset the Garlock, creating the now possibly inactive Mule Springs strand of the Garlock fault. Dextral slip on the Brown Mountain fault then locked the Owl Lake fault, forcing the active Leach Lake strand of the Garlock fault to break.
Central sensitization in tension-type headache--possible pathophysiological mechanisms.
Bendtsen, L
2000-06-01
The aim of the present thesis was to investigate the pathophysiology of chronic tension-type headache with special reference to central mechanisms. Increased tenderness to palpation of pericranial myofascial tissues is the most apparent abnormality in patients with tension-type headache. A new piece of equipment, a so-called palpometer, that makes it possible to control the pressure intensity exerted during palpation, was developed. Thereafter, it was demonstrated that the measurement of tenderness could be compared between two observers if the palpation pressure was controlled, and that the Total Tenderness Scoring system was well suited for the scoring of tenderness during manual palpation. Subsequently, it was found that pressure pain detection and tolerance thresholds were significantly decreased in the finger and tended to be decreased in the temporal region in chronic tension-type headache patients compared with controls. In addition, the electrical pain threshold in the cephalic region was significantly decreased in patients. It was concluded that the central pain sensitivity was increased in the patients probably due to sensitization of supraspinal neurones. The stimulus-response function for palpation pressure vs. pain was found to be qualitatively altered in chronic tension-type headache patients compared with controls. The abnormality was related to the degree of tenderness and not to the diagnosis of tension-type headache. In support of this, the stimulus-response function was found to be qualitatively altered also in patients with fibromyalgia. It was concluded that the qualitatively altered nociception was probably due to central sensitization at the level of the spinal dorsal horn/trigeminal nucleus. Thereafter, the prophylactic effect of amitriptyline, a non-selective serotonin (5-HT) reuptake inhibitor, and of citalopram, a highly selective 5-HT reuptake inhibitor, was examined in patients with chronic tension-type headache. Amitriptyline reduced headache significantly more than placebo, while citalopram had only a slight and insignificant effect. It was concluded that the blockade of 5-HT reuptake could only partly explain the efficacy of amitriptyline in tension-type headache, and that also other actions of amitriptyline, e.g. reduction of central sensitization, were involved. Finally, the plasma 5-HT level, the platelet 5-HT level and the number of platelet 5-HT transporters were found to be normal in chronic tension-type headache. On the basis of the present and previous studies, a pathophysiological model for tension-type headache is presented. According to the model, the main problem in chronic tension-type headache is central sensitization at the level of the spinal dorsal horn/trigeminal nucleus due to prolonged nociceptive inputs from pericranial myofascial tissues. The increased nociceptive input to supraspinal structures may in turn result in supraspinal sensitization. The central neuroplastic changes may affect the regulation of peripheral mechanisms and thereby lead to, for example, increased pericranial muscle activity or release of neurotransmitters in the myofascial tissues. By such mechanisms the central sensitization may be maintained even after the initial eliciting factors have been normalized, resulting in the conversion of episodic into chronic tension-type headache. Future basic and clinical research should aim at identifying the source of peripheral nociception in order to prevent the development of central sensitization and at ways of reducing established sensitization. This may lead to a much needed improvement in the treatment of chronic tension-type headache and other chronic myofascial pain conditions.
NASA Astrophysics Data System (ADS)
Amaya, Sergio; Zuluaga, Carlos Augusto; Bernet, Matthias
2017-06-01
The Late Cretaceous to late Neogene exhumation history of the central Santander Massif in the Northern Andes of Colombia is controlled by the geodynamic interactions between the Caribbean, South American and Nazca plates, as well as the Neogene collision and accretion of the Panama arc. Slab-breakoff of the Caribbean plate, with the tip of the slab tear presently being located beneath Bucaramanga, and the east-west oriented Caldas tear are the main structures relating seismic activity and Late Miocene to Pleistocene magmatic/hydrothermal activity and associated gold mineralization in the central Santander Massif. Here we present new apatite (AFT) and zircon fission-track (ZFT) data from 18 samples collected along two profiles in the California-Vetas block (including the Rio Charta), to the south of the Rio Charta fault, and from Bucaramanga to Picacho on the western flank of the central Santander Massif. The fission-track data are used for time-temperature history modelling and for estimating long-term average exhumation rates. The California-Vetas block in the central Santander Massif to the north of the Rio Charta fault cooled rapidly at a rate of about 24 °C/Myr between 10 and 5 Ma. Fast cooling was not related to post-magmatic cooling or hydrothermal activity, but rather to exhumation, with rates based on apatite fission-track cooling ages on the order of 0.3-0.4 km/Myr. However, long-term average exhumation rates since the Late Cretaceous, based on zircon fission-track data, were only on the order of 0.1-0.2 km/Myr. Our data indicate that next to the Rio Charta fault also the Surata fault contributed to the exhumation of the California-Vetas block. The western flank of the central Santander Massif, shows a more complete thermal history along the Bucaramanga-Picacho profile, with the exposure of an exhumed zircon fission-track partial annealing zone. Thermal history modelling of zircon fission-track data of this profile shows that after burial and heating from about 150 Ma on cooling at rates of 7-10 °C/Myr started at about 25 Ma. For the lower part of the profile, the early Miocene ZFT ages indicate exhumation at rates of 0.3-0.5 km/Myr along the Bucaramanga fault, but were only about 0.1 km/Myr on the high plateau of the central Santander Massif.
Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance
Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben
2015-01-01
Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pratt, B.L.; Takahashi, J.S.
The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxinmore » partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.« less
García-Pedraza, J A; García, M; Martín, M L; Rodríguez-Barbero, A; Morán, A
2016-04-01
The aim of this study was to determine whether orally sarpogrelate (selective 5-HT2 antagonist) treatment (30 mg/kg/day; 14 days) could modify 5-HT renal vasoconstrictor responses, characterizing 5-HT receptors and mediator mechanisms involved in serotonergic responses in the in situ autoperfused rat kidney. Intra-arterial (i.a.) injections of 5-HT (0.00000125 to 0.1 μg/kg) decreased renal perfusion pressure (RPP) but did not affect the mean blood pressure (MBP). i.a. agonists 5-CT (5-HT1/7), CGS-12066B (5-HT1B), L-694,247 (5-HT1D) or AS-19 (5-HT7) mimicked renal 5-HT vasodilator effect. However, neither 8-OH-DPAT (5-HT1A) nor 1-phenylbiguanide (5-HT3) modified RPP. Moreover: (i) GR-55562 (5-HT1B antagonist) and L-NAME (nitric oxide synthase [NOS] inhibitor) blocked CGS-12066B-induced vasodilator response, (ii) LY310762 (5-HT1D antagonist) and indomethacin (non-selective cyclooxygenase inhibitor) blocked L-694,247-induced vasodilator response; (iii) SB-258719 (5-HT7 antagonist) and glibenclamide (ATP-sensitive K+ channel blocker) blocked AS-19-induced vasodilator response; and (iv) 5-HT- or 5-CT-elicited renal vasodilation was significantly blocked by the mixture of GR-55562 + LY310762 + SB-258719. Furthermore, eNOS and iNOS proteins and prostacyclin levels are overexpressed in sarpogrelate-treated rats. Our data suggest that 5-HT exerts renal vasodilator effect in the in situ autoperfused sarpogrelate-treated rat kidney, mediated by 5-HT1D, 5-HT1B and 5-HT7 receptors, involving cyclooxygenase-derived prostacyclin, nitric oxide synthesis/release and ATP-sensitive K+ channels, respectively.
Comparison of Tarim and central Asian FSU basins, I: Phanerozoic paleogeography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heubeck, C.; Shangyou N.
1996-01-01
Large amounts of previously unpublished data on the petroleum geology of the FSU's Central Asian Republics and of China's Tarim region have found their way into the western public domain in the past few years. These data provide for the first time the opportunity to merge detailed stratigraphic, tectonic, and paleogeographic studies done during the past decades on both sides of the FSU-Chinese border and to place the results in a plate-tectonic and palinspastically restored reference frame. Major tectonic events affecting the active post-Silurian south-facing margin of Asia between the Caspian Sea and Tarim include (1) the collapse of themore » Kazakhstan arc fragments (ca. 400-300 Ma); (2) collision of YiIi with Tarim (ca. 375 Ma); (3) consolidation of the Turan Platform from pre-existing basement blocks (ca. 280-220 Ma), (4) collision of Tarim/Yili with the Kazakhstan arcs (ca. 260 Ma); (5) stabilization of a south-facing Triassic active margin (ca. 250 - 200 Ma); (6) accretion of Cimmeria (ca. 200 Ma) and associated reactivation events in Turan, Syr-Darja, and Tarim; (7) reactivation and modification of intracontinental structures during the collision of central Asia with India (ca. 55 Ma to present) and with the Arabian platform (ca. 25 Ma). Periodic large-scale flooding of denuded continental platforms (Turan, Tadjik) during sea-level highstands is recorded in the Jurassic, Mid-Late Cretaceous, and the Early Tertiary, resulting in extensive tracts of restricted marine sedimentary systems and marine incursions deep into central Asia (SW Tarim, Kuche Depression, Fergana, Turgay). Mesozoic-Cenozoic source rocks are sensitive to rapid lateral facies changes, and understanding their distribution requires detailed stratigraphic analysis. The attempted synthesis of data from China and the FSU with plate-tectonic concepts allows the transfer and testing of play concepts and hydrocarbons systems across the FSU-Chinese border.« less
Comparison of Tarim and central Asian FSU basins, I: Phanerozoic paleogeography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heubeck, C.; Shangyou N.
1996-12-31
Large amounts of previously unpublished data on the petroleum geology of the FSU`s Central Asian Republics and of China`s Tarim region have found their way into the western public domain in the past few years. These data provide for the first time the opportunity to merge detailed stratigraphic, tectonic, and paleogeographic studies done during the past decades on both sides of the FSU-Chinese border and to place the results in a plate-tectonic and palinspastically restored reference frame. Major tectonic events affecting the active post-Silurian south-facing margin of Asia between the Caspian Sea and Tarim include (1) the collapse of themore » Kazakhstan arc fragments (ca. 400-300 Ma); (2) collision of YiIi with Tarim (ca. 375 Ma); (3) consolidation of the Turan Platform from pre-existing basement blocks (ca. 280-220 Ma), (4) collision of Tarim/Yili with the Kazakhstan arcs (ca. 260 Ma); (5) stabilization of a south-facing Triassic active margin (ca. 250 - 200 Ma); (6) accretion of Cimmeria (ca. 200 Ma) and associated reactivation events in Turan, Syr-Darja, and Tarim; (7) reactivation and modification of intracontinental structures during the collision of central Asia with India (ca. 55 Ma to present) and with the Arabian platform (ca. 25 Ma). Periodic large-scale flooding of denuded continental platforms (Turan, Tadjik) during sea-level highstands is recorded in the Jurassic, Mid-Late Cretaceous, and the Early Tertiary, resulting in extensive tracts of restricted marine sedimentary systems and marine incursions deep into central Asia (SW Tarim, Kuche Depression, Fergana, Turgay). Mesozoic-Cenozoic source rocks are sensitive to rapid lateral facies changes, and understanding their distribution requires detailed stratigraphic analysis. The attempted synthesis of data from China and the FSU with plate-tectonic concepts allows the transfer and testing of play concepts and hydrocarbons systems across the FSU-Chinese border.« less
Paci, M; Hyttinen, J; Rodriguez, B
2015-01-01
Background and Purpose Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and in silico human adult ventricular cardiomyocyte (hAdultV‐CM) models. Their combination was recently proposed as a potential replacement for the present hERG‐based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC‐CM and hAdultV‐CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. Experimental Approach In silico AP models of ventricular‐like and atrial‐like hiPSC‐CMs and hAdultV‐CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. Key Results Qualitatively, hiPSC‐CM and hAdultV‐CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC‐CMs were more sensitive to block of (i) L‐type Ca2+ currents due to the overexpression of the Na+/Ca2+ exchanger (leading to shorter APs) and (ii) the inward rectifier K+ current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). Conclusions and Implications In silico hiPSC‐CMs and hAdultV‐CMs exhibit a similar response to selective current blocks. However, overall hiPSC‐CMs show greater sensitivity to block, which may facilitate in vitro identification of drug‐induced effects. Extrapolation of drug effects from hiPSC‐CM to hAdultV‐CM and pro‐arrhythmic risk assessment can be facilitated by in silico predictions using biophysically‐based computational models. PMID:26276951
Heather T. Root; Bruce McCune; Sarah Jovan
2014-01-01
Because of their unique physiology, lichen communities are highly sensitive to climatic conditions,making them ideal bioindicators for climate change. Southeast and south-central Alaska host diverse and abundant lichen communities and are faced with a more rapidly changing climate than many more southerly latitudes. We develop sensitive lichen-based indicators for...
Manyazewal, Tsegahun
2017-01-01
Acknowledging the health system strengthening agenda, the World Health Organization (WHO) has formulated a health systems framework that describes health systems in terms of six building blocks. This study aimed to determine the current status of the six WHO health system building blocks in public healthcare facilities in Ethiopia. A quantitative, cross-sectional study was conducted in five public hospitals in central Ethiopia which were in a post-reform period. A self-administered, structured questionnaire which covered the WHO's six health system building blocks was used to collect data on healthcare professionals who consented. Data was analyzed using IBM SPSS version 20. The overall performance of the public hospitals was 60% when weighed against the WHO building blocks which, in this procedure, needed a minimum of 80% score. For each building block, performance scores were: information 53%, health workforce 55%, medical products and technologies 58%, leadership and governance 61%, healthcare financing 62%, and service delivery 69%. There existed a significant difference in performance among the hospitals ( p < .001). The study proved that the WHO's health system building blocks are useful for assessing the process of strengthening health systems in Ethiopia. The six blocks allow identifying different improvement opportunities in each one of the hospitals. There was no contradiction between the indicators of the WHO building blocks and the health sustainable development goal (SDG) objectives. However, such SDG objectives should not be a substitute for strategies to strengthen health systems.
The interaction of cadmium with atrial natriuretic factor: A study in in vivo and in vitro models
DOE Office of Scientific and Technical Information (OSTI.GOV)
Giridhar, J.
1990-01-01
The involvement of atrial natriuretic factor (ANF) and its receptor in cadmium(Cd)-induced cardiovascular alterations and neurotoxicity is not known. This study examines the mechanisms underlying Cd-induced changes in the ANF peptide and its receptor in cardiovascular toxicity. In rats on short term Cd exposure (0.01, 0.1, 0.5 and 1.0 mg/kg, i.p., twice a day for 7 days and a maintenance period of 30 days), atrial ANF levels decreased significantly in the Cd 1 mg/kg group; plasma ANF levels were unchanged. Hypothalamic ANF content decreased significantly in 0.1-1.0 mg/kg Cd groups. Plasma renin activity and concentration were unchanged by Cd treatment.more » However, plasma aldosterone was significantly decreased in Cd 1.0 mg/kg group. Binding of [sup 125]I-ANF to its receptors in kidney, adrenals and aorta was not significantly altered. Cd treatment decreased urine volume indicating nephrotoxicity. Neuromodulation by ANF involved significant decrease in K[sup +] stimulated [[sup 3]H]NE release in rat hypothalamic slices. This action is proposed to be mediated by ANF-B receptors. 8Br-cGMP mimicked this action. In Cd treated animals (0.5 mg/kg twice a day for 7 days and maintained for 30 days), ANF neuromodulation in the hypothalmus was blocked, even though Cd content was undetectable. Cd preincubated (0.5 mM) slices showed a 49.1% block in neurotransmitter release indicating that Cd may block calcium channels leading to decreased K[sup +]-stimulated release of [[sup 3]H]NE. Hence, Cd-induced cardiovascular toxicity and neurotoxicity may be partly mediated by alteration in the release and possibly the synthesis of ANF peptide, disruption of ANF function through alterations in receptor dynamics and possibly alteration in cellular calcium homeostasis and membrane integrity. Central ANF function is sensitive to Cd and this effect may be partly resposible for the cardiovascular and neurotoxic responses to CD.« less
Genesis of iron-apatite ores in Posht-e-Badam Block (Central Iran) using REE geochemistry
NASA Astrophysics Data System (ADS)
Mokhtari, Mir Ali Asghar; Zadeh, Ghader Hossein; Emami, Mohamad Hashem
2013-06-01
Rare earth elements in apatites of different ore types show characteristic patterns which are related to different modes of formation of the ores. Most of the apatite-bearing iron ores are associated with alkaline magmas with LREE/HREE fractionation varying from moderate to steep. Iron-apatite deposits in Posht-e-Badam Block (Central Iran) have a high concentration of REE (more than 1000 ppm up to 2.5%), and show a strong LREE/HREE ratio with a pronounced negative Eu anomaly. This REE pattern is typical of magmatic apatite and quiet distinct from sedimentary apatites (phosphorites) which have a low REE contents and Ce negative anomalies. On the other hand, they are comparable to the REE patterns of apatites in Kiruna-type iron ores in different parts of the world. The REE patterns of apatites, iron-apatite ores and iron ores are similar and only have different REE contents. This similarity indicates a genetic relation for these rocks. Most of the iron-apatite deposits in Central Iran have similar REE patterns too, which in turn show a genetic relation for all of these deposits. This similarity indicates a similar origin and processes in their genesis. There are some small intrusions around some of the iron-apatite deposits that are petrographically identified as syenite and gabbro. These intrusions also have REE patterns similar to that of iron-apatite ores. This demonstrates a genetic relation between these intrusions and iron-apatite ores. The REE patterns of apatites in different deposits of Posht-e-Badam Block iron-apatite ores show an affinity to alkaline to sub-alkaline magmas and rifting environment. The alkaline host rocks of Central Iran iron-apatite ores are clearly related to an extensional setting where rifting was important (SSE-NNW fault lines). A probable source for this large scale ore forming processes is relatively low partial melting of mantle rocks. The ores have originated by magmatic differentiation as a late phase in the volcanic cycle forming sub-surface injections or surface flows. These ores have formed during magmatism as immiscible liquids (silicate and Fe-P-rich magmatic liquids) which separated from strongly differentiated magmas aided by a large volatile and alkali element content. Separation of an iron oxide melt and the ensuing hydrothermal processes dominated by alkali metasomatism were both involved to different degrees in the formation of Posht-e-Badam Block iron-apatite deposits. We proposed that the separation of an iron oxide melt and the ensuing hydrothermal processes dominated by alkali metasomatism were both involved to different degrees in the formation of Posht-e-Badam Block iron-apatite deposits.
Zhang, Xiao; Liu, Jian Jun; Fang Sum, Chee; Ying, Yeoh Lee; Tavintharan, Subramaniam; Ng, Xiao Wei; Su, Chang; Low, Serena; Lee, Simon Bm; Tang, Wern Ee; Lim, Su Chi
2016-07-01
To examine the relationship between inflammation and central arterial stiffness in a type 2 diabetes Asian cohort. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index. Linear regression model was used to evaluate the association of high-sensitivity C-reactive protein and soluble receptor for advanced glycation end products with pulse wave velocity and augmentation index. High-sensitivity C-reactive protein was analysed as a continuous variable and categories (<1, 1-3, and >3 mg/L). There is no association between high-sensitivity C-reactive protein and pulse wave velocity. Augmentation index increased with high-sensitivity C-reactive protein as a continuous variable (β = 0.328, p = 0.049) and categories (β = 1.474, p = 0.008 for high-sensitivity C-reactive protein: 1-3 mg/L and β = 1.323, p = 0.019 for high-sensitivity C-reactive protein: >3 mg/L) after multivariable adjustment. No association was observed between augmentation index and soluble receptor for advanced glycation end products. Each unit increase in natural log-transformed soluble receptor for advanced glycation end products was associated with 0.328 m/s decrease in pulse wave velocity after multivariable adjustment (p = 0.007). Elevated high-sensitivity C-reactive protein and decreased soluble receptor for advanced glycation end products are associated with augmentation index and pulse wave velocity, respectively, suggesting the potential role of systemic inflammation in the pathogenesis of central arterial stiffness in type 2 diabetes. © The Author(s) 2016.
NASA Astrophysics Data System (ADS)
Zhang, Letian
2017-09-01
The Asian continent was formed through the amalgamation of several major continental blocks that were formerly separated by the Paleo-Asian and Tethyan Oceans. During this process, the Asian continent underwent a long period of continental crustal growth and tectonic deformation, making it the largest and youngest continent on Earth. This paper presents a review of the application of geophysical electromagnetic methods, mainly the magnetotelluric (MT) method, in recent investigations of the diverse tectonic features across the Asian continent. The case studies cover the major continental blocks of Asia, the Central Asian orogenic system, the Tethyan orogenic system, as well as the western Pacific subduction system. In summary, most of the major continental blocks of Asia exhibit a three-layer structure with a resistive upper crust and upper mantle and a relatively conductive mid-lower crust. Large-scale conductors in the upper mantle were interpreted as an indication of lithospheric modification at the craton margins. The electrical structure of the Central Asian orogenic system is generally more resistive than the bordering continental blocks, whereas the Tethyan orogenic system displays more conductive, with pervasive conductors in the lower crust and upper mantle. The western Pacific subduction system shows increasing complexity in its electrical structure from its northern extent to its southern extent. In general, the following areas of the Asian continent have increasingly conductive lithospheric electrical structures, which correspond to a transition from the most stable areas to the most active tectonic areas of Asia: the major continental blocks, the accretionary Central Asian orogenic system, the collisional Tethyan orogenic system, and the western Pacific subduction system. As a key part of this review, a three-dimensional (3-D) model of the lithospheric electrical structure of a large portion of the Tibetan Plateau is presented and discussed in detail; the model indicates tearing of the underthrusting Indian slab as well as complex crustal conductor geometries, which are not obviously consistent with the hypothesis of a continuous, eastward channel flow. These studies have greatly enhanced our knowledge of the formation and deformation processes of the Asian continent. Lastly, future research to expand field data coverage, improve related techniques, and integrate data from other disciplines is suggested.
NASA Astrophysics Data System (ADS)
Zanchetta, Stefano; Worthington, James; Angiolini, Lucia; Zanchi, Andrea
2017-04-01
The Pamir belts, located NW of the Himalaya, formed in response to the Cenozoic collision and indentation of India with Eurasia. Several crustal blocks separated by complex and scarcely studied suture zones form the present day tectonic architecture of the Pamirs. The extreme crustal shortening resulted in strong deformation and bending of pre-existing Paleozoic to Mesozoic orogens. Such deformation hinders straightforward correlations between tectonic terranes of the Himalaya-Tibetan area with their potential continuations through the Pamirs into Afghanistan and Iran. Central and SE Pamir, together with Karakoram and Qiangtang blocks separated from the Gondwana margin in the Early Permian, drifted northward, following the closure of the Paleotethys and other minor oceanic branches, and diachronously collided with Northern Pamir and Tian Shan. The Central and South Pamir are now separated by the poorly known Rushan-Pshart Suture Zone. South Pamir is separated into two units: SE Pamir consists of a Permian to Cenozoic sedimentary succession; SW Pamir is instead made of gigantic basement domes that are in contact with the SE block along crustal scale detachments. In SE Pamir, intensively folded and faulted Permian and Triassic units are unconformably covered by lowermost Jurassic terrigeneous deposits, testifying for Middle to Lower Triassic tectonics related to the Cimmerian orogenic events. Along the contact between the SE and SW Pamir, a small (a few tens of km2 wide) magmatic-metasedimetary unit occurs, reported in literature as the Bashgumbaz ophiolites. They consist of a low-grade metamorphic association of serpentinized harzburgites and gabbros, minor bodies of diorite and plagiogranite, basalts and intermediate volcanic rocks, metasediments, and a flyschoid unit containing olistolithic blocks with Triassic faunas attributed to Central Pamir block. Petrographic and geochemical data suggest a supra-subduction zone affinity for the gabbroic complex. U-Th-Pb dating of zircons from a diorite provides a Carnian crystallization age. Deformation and metamorphism (up to greenschist facies) that affected the Bashgumbaz complex should therefore been placed in the Late Triassic. We suggest that the Bashgumbaz unit formed in a supra-subduction setting and was later underthrusted and then obducted onto the southern margin of the closing Rushan-Pshart ocean. The obduction of the Bashgumbaz ophiolites could be considered as a time-marker for the accretion of the South Pamir terrane to the Eurasian margin.
Effect of Long Term Low-Level Gamma Radiation on Thermal Sensitivity of RDX/HMX Mixtures
1976-11-01
1.1x10 R. It was concluded that the slight exothermic reaction before the 3^6 HMX polymorphic transition could be caused by a radiation-induced...Radiation on Thermal Sensitivity of RDX / HMX Mixtures 5. TYPE OF REPORT 4 PERIOD COVERED Final Report 6. PERFORMING ORG. REPORT NUMBER 7...and Identity by block number) Gamma radiation Weight loss HMX Impact sensitivity test RDX Vacuum stability test DTA Infrared spectrometry TGA
25. May 1985. DETAIL OF CELLAR STEPS AND EARTH WALL ...
25. May 1985. DETAIL OF CELLAR STEPS AND EARTH WALL OF CELLAR IN CENTRAL BLOCK - Borough House, West Side State Route 261, about .1 mile south side of junction with old Garners Ferry Road, Stateburg, Sumter County, SC
ERIC Educational Resources Information Center
Roscoe, Matt B.; Zephyrs, Joe
2016-01-01
Geometric transformations have long been topics of middle school mathematics. Generations of middle school students have learned to reflect, rotate, and translate geometric objects. Historically, though, the mathematics of "movement" might have been considered a departure from other more central middle-grades geometric content areas,…
Georgiev, Nikolai I; Bryaskova, Rayna; Tzoneva, Rumiana; Ugrinova, Iva; Detrembleur, Christophe; Miloshev, Stoyan; Asiri, Abdullah M; Qusti, Abdullah H; Bojinov, Vladimir B
2013-11-01
Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide-rhodamine bichromophoric FRET system (RNI) to the PMMA block of a well-defined amphiphilic diblock copolymer-poly(methyl methacrylate)-b-poly(methacrylic acid) (PMMA48-b-PMAA27). The RNI-PMMA48-b-PMAA27 adduct is capable of self-assembling into micelles with a hydrophobic PMMA core, containing the anchored fluorescent probe, and a hydrophilic shell composed of PMAA block. Novel fluorescent micelles are able to serve as a highly sensitive pH probe in water and to internalize successfully HeLa and HEK cells. Furthermore, they showed cell specificity and significantly higher photostability than that of a pure organic dye label such as BODIPY. The valuable properties of the newly prepared fluorescent micelles indicate the high potential of the probe for future biological and biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.
Measurement of Systematic Error Effects for a Sensitive Storage Ring EDM Polarimeter
NASA Astrophysics Data System (ADS)
Imig, Astrid; Stephenson, Edward
2009-10-01
The Storage Ring EDM Collaboration was using the Cooler Synchrotron (COSY) and the EDDA detector at the Forschungszentrum J"ulich to explore systematic errors in very sensitive storage-ring polarization measurements. Polarized deuterons of 235 MeV were used. The analyzer target was a block of 17 mm thick carbon placed close to the beam so that white noise applied to upstream electrostatic plates increases the vertical phase space of the beam, allowing deuterons to strike the front face of the block. For a detector acceptance that covers laboratory angles larger than 9 ^o, the efficiency for particles to scatter into the polarimeter detectors was about 0.1% (all directions) and the vector analyzing power was about 0.2. Measurements were made of the sensitivity of the polarization measurement to beam position and angle. Both vector and tensor asymmetries were measured using beams with both vector and tensor polarization. Effects were seen that depend upon both the beam geometry and the data rate in the detectors.
Dunkel, Christian; von Graberg, Till; Smarsly, Bernd M.; Oekermann, Torsten; Wark, Michael
2014-01-01
Well-ordered 3D mesoporous indium tin oxide (ITO) films obtained by a templated sol-gel route are discussed as conductive porous current collectors. This paper explores the use of such films modified by electrochemical deposition of zinc oxide (ZnO) on the pore walls to improve the electron transport in dye-sensitized solar cells (DSSCs). Mesoporous ITO film were dip-coated with pore sizes of 20–25 nm and 40–45 nm employing novel poly(isobutylene)-b-poly(ethylene oxide) block copolymers as structure-directors. After electrochemical deposition of ZnO and sensitization with the indoline dye D149 the films were tested as photoanodes in DSSCs. Short ZnO deposition times led to strong back reaction of photogenerated electrons from non-covered ITO to the electrolyte. ITO films with larger pores enabled longer ZnO deposition times before pore blocking occurred, resulting in higher efficiencies, which could be further increased by using thicker ITO films consisting of five layers, but were still lower compared to nanoporous ZnO films electrodeposited on flat ITO. The major factors that currently limit the application are the still low thickness of the mesoporous ITO films, too small pore sizes and non-ideal geometries that do not allow obtaining full coverage of the ITO surface with ZnO before pore blocking occurs. PMID:28788618
Prabhu, Sundararaman; Faizel, Syed; Pahlajani, Vedant; Prabhu, Shweta Jha
2013-12-01
This study was conducted to compare and evaluate the pain associated with administration of Nasopalatine blocks using a disposable insulin syringe and the conventional disposable 3 mL syringe. Forty patients requiring intraalveolar extractions of maxillary central incisors were randomly assigned to two groups of 20 patients each; one (Group A) received the nasopalatine block with a standard 3mL syringe and the other (Group B) received the block with an insulin syringe. Patients were asked to rate the pain associated with the injection on a visual analog scale (VAS) and the results were analysed using a Chi Square Test. The mean VAS score for Group A and B was 1.55 and 1 respectively. Chi Square value was calculated to be 8.603 (degree of freedom= 3, P value= 0.0351). There were no differences in the effectiveness of anesthesia between the groups. Pain associated with administration of the nasopalatine blocks may be significantly mitigated by using the Insulin syringe.
NASA Astrophysics Data System (ADS)
Conway, Kim W.; Vaughn Barrie, J.
2018-01-01
Very large (>60×106 m3) sackungen or deep-seated gravitational slope deformations occur below sea level along a steep fjord wall in central Douglas Channel, British Columbia. The massive bedrock blocks were mobile between 13 and 11.5 thousand radiocarbon years BP (15,800 and 13,400 BP) immediately following deglaciation. Deformation of fjord sediments is apparent in sedimentary units overlying and adjacent to the blocks. Faults bound the edges of each block, cutting the glacial section but not the Holocene sediments. Retrogressive slides, small inset landslides as well as incipient and older slides are found on and around the large failure blocks. Lineations, fractures and faults parallel the coastline of Douglas Channel along the shoreline of the study area. Topographic data onshore indicate that faults and joints demarcate discrete rhomboid-shaped blocks which controlled the form, size and location of the sackungen. The described submarine sackungen share characteristic geomorphic features with many montane occurrences, such as uphill-facing scarps, foliated bedrock composition, largely vertical dislocation and a deglacial timing of development.
NASA Astrophysics Data System (ADS)
Conway, Kim W.; Vaughn Barrie, J.
2018-06-01
Very large (>60×106 m3) sackungen or deep-seated gravitational slope deformations occur below sea level along a steep fjord wall in central Douglas Channel, British Columbia. The massive bedrock blocks were mobile between 13 and 11.5 thousand radiocarbon years BP (15,800 and 13,400 BP) immediately following deglaciation. Deformation of fjord sediments is apparent in sedimentary units overlying and adjacent to the blocks. Faults bound the edges of each block, cutting the glacial section but not the Holocene sediments. Retrogressive slides, small inset landslides as well as incipient and older slides are found on and around the large failure blocks. Lineations, fractures and faults parallel the coastline of Douglas Channel along the shoreline of the study area. Topographic data onshore indicate that faults and joints demarcate discrete rhomboid-shaped blocks which controlled the form, size and location of the sackungen. The described submarine sackungen share characteristic geomorphic features with many montane occurrences, such as uphill-facing scarps, foliated bedrock composition, largely vertical dislocation and a deglacial timing of development.
Ultraviolet vision in birds: the importance of transparent eye media
Lind, Olle; Mitkus, Mindaugas; Olsson, Peter; Kelber, Almut
2014-01-01
Ultraviolet (UV)-sensitive visual pigments are widespread in the animal kingdom but many animals, for example primates, block UV light from reaching their retina by pigmented lenses. Birds have UV-sensitive (UVS) visual pigments with sensitivity maxima around 360–373 nm (UVS) or 402–426 nm (violet-sensitive, VS). We describe how these pigments are matched by the ocular media transmittance in 38 bird species. Birds with UVS pigments have ocular media that transmit more UV light (wavelength of 50% transmittance, λT0.5, 323 nm) than birds with VS pigments (λT0.5, 358 nm). Yet, visual models predict that colour discrimination in bright light is mostly dependent on the visual pigment (UVS or VS) and little on the ocular media. We hypothesize that the precise spectral tuning of the ocular media is mostly relevant for detecting weak UV signals, e.g. in dim hollow-nests of passerines and parrots. The correlation between eye size and UV transparency of the ocular media suggests little or no lens pigmentation. Therefore, only small birds gain the full advantage from shifting pigment sensitivity from VS to UVS. On the other hand, some birds with VS pigments have unexpectedly low UV transmission of the ocular media, probably because of UV blocking lens pigmentation. PMID:24258716
Ultraviolet vision in birds: the importance of transparent eye media.
Lind, Olle; Mitkus, Mindaugas; Olsson, Peter; Kelber, Almut
2014-01-07
Ultraviolet (UV)-sensitive visual pigments are widespread in the animal kingdom but many animals, for example primates, block UV light from reaching their retina by pigmented lenses. Birds have UV-sensitive (UVS) visual pigments with sensitivity maxima around 360-373 nm (UVS) or 402-426 nm (violet-sensitive, VS). We describe how these pigments are matched by the ocular media transmittance in 38 bird species. Birds with UVS pigments have ocular media that transmit more UV light (wavelength of 50% transmittance, λ(T0.5), 323 nm) than birds with VS pigments (λ(T0.5), 358 nm). Yet, visual models predict that colour discrimination in bright light is mostly dependent on the visual pigment (UVS or VS) and little on the ocular media. We hypothesize that the precise spectral tuning of the ocular media is mostly relevant for detecting weak UV signals, e.g. in dim hollow-nests of passerines and parrots. The correlation between eye size and UV transparency of the ocular media suggests little or no lens pigmentation. Therefore, only small birds gain the full advantage from shifting pigment sensitivity from VS to UVS. On the other hand, some birds with VS pigments have unexpectedly low UV transmission of the ocular media, probably because of UV blocking lens pigmentation.
Wu, Qingwei; Zhao, Yingying; Wang, Peihua
2018-03-01
This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Momin, Eric N; Recinos, Pablo F; Coon, Alexander L; Rigamonti, Daniele
2010-06-01
Ventriculoatrial (VA) shunting is commonly used to treat hydrocephalus when ventriculoperitoneal shunting has failed. Placement of a VA shunt in patients with narrowing or occlusion of the central veins presents considerable difficulty because few imaging modalities exist to safely and reliably insert a guidewire or atrial catheter past the occlusion. We report the use of intraoperative venography to guide the placement of the distal portion of a VA shunt in a patient with a valve blocking the left brachiocephalic vein. A 42-year-old man with pseudotumor cerebri and a left ventriculoperitoneal shunt presented with severe headaches. He was diagnosed with partial distal shunt obstruction. Because of a history of failed attempts at ventriculoperitoneal shunting, conversion to a VA shunt via the left internal jugular vein was planned. Surgery was performed by using the standard technique until resistance was encountered when inserting a guidewire into the internal jugular vein. Intraoperative venography of the central veins was performed, which showed a large valve blocking progression of the guidewire in the left brachiocephalic vein. Using fluoroscopic guidance, a 0.035-inch guidewire was successfully directed through the vein past the obstruction and exchanged for a peel-away introducer. The distal shunt catheter was then inserted, and the correct position in the atrium was confirmed fluoroscopically. When obstruction of the central veins is found during a VA shunting procedure, intraoperative venography is a useful method to aid in the placement of the atrial catheter through the central veins.
Eandi, Chiara M; Piccolino, Felice Cardillo; Alovisi, Camilla; Tridico, Federico; Giacomello, Daniela; Grignolo, Federico M
2015-04-01
To find possible correlations between the morphologic macular changes revealed by fundus autofluorescence (FAF) and the functional parameters such as visual acuity and retinal sensitivity in patients with chronic central serous chorioretinopathy (CSC). Prospective, cross-sectional study. Forty-six eyes (39 consecutive patients) with chronic CSC were studied with FAF and microperimetry (MP). Retinal sensitivity value maps were exactly superimposed over FAF images. The following microperimetric parameters were applied: central 10-degree visual field, 4-2-1 strategy, 61 stimulation spots, white monochromatic background, stimulation time 200 ms, stimulation spot size Goldmann III. A possible relationship between MP and FAF was investigated. Mean best-corrected visual acuity (BCVA) was 20/32 (median 20/25, range 20/20-20/200). BCVA was significantly correlated with FAF findings (Mann-Whitney test; P < .0001). A positive concordance between FAF and MP evaluation was also found (total concordance of 0.720 with a kappa of Cohen of 0.456). The hypo-autofluorescent areas showed decreased retinal sensitivity, while adjacent areas of increased FAF could be associated to both normal and decreased retinal sensitivity. Absolute scotoma, defined as 0 dB retinal sensitivity, corresponded with absence of autofluorescence. Altered FAF in chronic CSC patients has a functional correlation quantified by microperimetry. This study confirms the impact of FAF changes on retinal sensitivity and their value to reflect the functional impairment in chronic CSC. Copyright © 2015 Elsevier Inc. All rights reserved.
Ezenwa, Miriam O.; Molokie, Robert E.; Wang, Zaijie Jim; Yao, Yingwei; Suarez, Marie L.; Pullum, Cherese; Schlaeger, Judith M.; Fillingim, Roger B.; Wilkie, Diana J.
2014-01-01
Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N=25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n=15), peripheral sensitization (n=1), a mix of central and peripheral sensitization (n=8), or no sensitization (n=1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults. PMID:25581383
Central anticholinergic syndrome: a case report.
Moos, Daniel D
2007-10-01
Postoperative central anticholinergic syndrome (CAS) is caused by anticholinergic medications that cross the blood-brain barrier. Medications with central anticholinergic effects block muscarinic cholinergic receptors, resulting in a wide array of symptoms. Symptoms may range from coma to a highly agitated state. CAS may be underdiagnosed because of its varying presentation and lack of awareness. Differential diagnosis for the patient presenting with abnormal neurological signs and symptoms should include CAS after the exclusion of other potential causes. This case report details the occurrence of CAS in a patient in her 20's. A review of CAS including causes, signs and symptoms, incidence, differential diagnosis, and treatment is discussed.
Sensitization of meningeal nociceptors: inhibition by naproxen
Levy, Dan; Zhang, Xi-Chun; Jakubowski, Moshe; Burstein, Rami
2009-01-01
Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of Aδ- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of Aδ- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. PMID:18333963
Sung, Ki Hyuk; Choi, Young; Cho, Gyeong Hee; Chung, Chin Youb; Park, Moon Seok; Lee, Kyoung Min
2018-02-05
This study evaluated the correlation between central and peripheral bone mineral density (BMD) of the ankle joint, using dual-energy X-ray absorptiometry (DXA). We also investigated whether peripheral ankle BMD could be used to identify individuals who were diagnosed with osteoporosis, using central DXA. We recruited 134 volunteers aged 20-90 years who agreed to participate in this study. Central BMD of the lumbar spine and left femur, and peripheral BMD of the medial malleolus, distal tibia, lateral malleolus, and talus were measured with DXA. Among the peripheral sites of the ankle, the highest and lowest BMD were observed in the talus and lateral malleolus, respectively. All peripheral DXA measurements of the ankle joint were significantly correlated with central DXA measurements. There was a good correlation (r: 0.656-0.725) between peripheral and central BMD for the older age group (> 50 years), but fair-to-good correlation (r: 0.263-0.654) for the younger age group (< 50 years). The cut-off values for peripheral BMD of the ankle joint between osteoporosis and non-osteoporosis were 0.548 g/cm 2 (sensitivity, 89.0%; specificity, 69.0%) for the medial malleolus, 0.626 g/cm 2 (sensitivity, 83.3%; specificity, 82.8%) for the distal tibia, 0.47 g/cm 2 (sensitivity, 100.0%; specificity, 65.5%) for the lateral malleolus, and 0.973 g/cm 2 (sensitivity, 72.2%; specificity, 83.6%) for the talus (p < 0.001). This study showed good correlation between peripheral BMD around ankle joint and central BMD for older age group. Further study is required to use the ankle DXA as a valid clinical tool for the diagnosis of osteoporosis and fracture risk assessment.
Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.
Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M
2016-07-01
Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Mechanisms of thermal acclimation to exercise and heat
NASA Technical Reports Server (NTRS)
Nadel, E. R.; Pandolf, K. B.; Roberts, M. F.; Stolwijk, J. A. J.
1974-01-01
By plotting local sweating rate from a given area against the central sweating drive (which is analogous to esophageal temperature, when mean skin temperature is constant), it is possible to determine the characteristic gain constant of that area as well as its point of zero central drive. An increase in the gain constant as a result of acclimation would indicate an increased sensitivity of the sweating mechanism per unit of central sweating drive, i.e., enhanced peripheral sensitivity. A displacement of the point of zero central drive as a result of acclimation would indicate that central mechanisms are responsible for the heightened sweating response. The study was undertaken to provide information about whether central or peripheral physiological mechanisms provide for increased sweating capabilities during acclimation, and about whether the increased sweating capabilities in heat acclimation and physical training are provided for by the same mechanisms.
2014-12-01
7. 248 A great deal of uncertainty surrounds the incident as the government suppressed media reporting and blocked all forms of communication ... A Post-2014 Strategy for Central Asia. Carlisle, PA: Army War College , 2012. http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html...Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the
Rheology of polyelectrolyte complex materials
NASA Astrophysics Data System (ADS)
Tirrell, Matthew
Fluid polyelectrolyte complexes, sometimes known as complex coacervates, have rheological properties that are very sensitive to structure and salt concentration. Dynamic moduli of such viscoelastic materials very many orders of magnitude between solutions of no added salt to of order tenth molar salt, typical, for example of physiological saline. Indeed, salt plays a role in the rheology of complex coacervates analogous to that which temperature plays on polymer melts, leading to an empirical observation of what may be termed time-salt or frequency salt superposition. Block copolymers containing complexing ionic blocks also exhibit strong salt sensitivity of their rheological properties. Data representing these phenomena will be presented and discussed. Support from NIST, Department of Commerce, via the Center for Hierarchical Materials Design at Northwestern University and the University of Chicago is gratefully acknowledged.
Era, P; Pärssinen, O; Pykälä, P; Jokela, J; Suominen, H
1994-10-01
The sensitivity of the central visual field (0 degree-30 degrees) was studied using an automatic Octopus 500E perimeter in elderly male athletes and in a population sample of men of corresponding age. The athletes (N = 96) were endurance and power athletes, who were still active in competitive sports with training histories spanning tens of years. The athletes' results were compared with those of a sample of men of the same age (70-81 years, N = 41) randomly selected from the local population register. The sensitivity values of the athletes, and the endurance athletes in particular, were significantly better than those of the controls, with differences varying from 1 to 2.5 dB in the different areas of the central visual field. Multivariate analyses of the background factors of visual field sensitivity showed that the most important were age, amount of annual training, number of chronic diseases, HDL-cholesterol level, and vital capacity. The results suggest that a long training history, especially of the aerobic type, may be beneficial with respect to the sensitivity of the visual system.
Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige
2005-05-01
The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.
Meeus, Mira
2006-01-01
In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc. PMID:17115100
NASA Astrophysics Data System (ADS)
Guo, Wenzhang; Wang, Hao; Wu, Zhengping
2018-03-01
Most existing cascading failure mitigation strategy of power grids based on complex network ignores the impact of electrical characteristics on dynamic performance. In this paper, the robustness of the power grid under a power decentralization strategy is analysed through cascading failure simulation based on AC flow theory. The flow-sensitive (FS) centrality is introduced by integrating topological features and electrical properties to help determine the siting of the generation nodes. The simulation results of the IEEE-bus systems show that the flow-sensitive centrality method is a more stable and accurate approach and can enhance the robustness of the network remarkably. Through the study of the optimal flow-sensitive centrality selection for different networks, we find that the robustness of the network with obvious small-world effect depends more on contribution of the generation nodes detected by community structure, otherwise, contribution of the generation nodes with important influence on power flow is more critical. In addition, community structure plays a significant role in balancing the power flow distribution and further slowing the propagation of failures. These results are useful in power grid planning and cascading failure prevention.
NASA Astrophysics Data System (ADS)
Fazzito, Sabrina Y.; Rapalini, Augusto E.
2016-10-01
The widespread Sanrafaelic remagnetization reset most of the early Cambrian to mid-Ordovician carbonate platform of the Argentine Precordillera and the calcareous units of the San Rafael Block. We conducted a detailed rock-magnetic study on the Middle-Ordovician limestones of the Ponón Trehué Formation at both limbs of a tight anticline exposed in the San Rafael Block (Mendoza province, central-western Argentina) that are carriers of a syntectonic magnetization of Permian age. We found that the magnetic overprint in the Ponón Trehué Formation is carried by both pyrrhotite and magnetite, with goethite and subordinate haematite likely related to weathering. Hysteresis parameters, frequency dependence of magnetic susceptibility, Cisowski and modified Lowrie-Fuller tests suggest the presence of ultrafine particles of chemical origin. Demagnetization of natural remanent magnetization and of three-axis isothermal remanence confirm pyrrhotite and magnetite as important contributors to the remanence. Both minerals carry the same magnetic syntectonic component suggesting a coeval or nearly coeval remanence acquisition and therefore mineral formation. This and the results of the magnetic fabric analyses indicate an authigenic origin of the magnetic minerals during folding associated with the Sanrafaelic tectonic phase (ca. 280 Ma). Although the chemically active (oxidizing?) fluids expelled from the orogen as it developed in the early Permian is a viable explanation for the Sanrafaelic remagnetization, the role of the nearly coeval magmatism in Precordillera and the San Rafael Block remains to be properly evaluated.
Paleomagnetic evidence that the central block of Salinia (California) is not a far-traveled terrane
Whidden, K.J.; Lund, S.P.; Bottjer, D.J.; Champion, D.; Howell, D.G.
1998-01-01
New paleomagnetic results from Late Cretaceous (75-85 m.y.) red beds on the central block of Salinia indicate that Salinia was located within 6?? (in latitude) of its current cratonal North American position during the Late Cretaceous (after correction for Neogene San Andreas Fault transport). The red beds formed as alluvial-fan overbank deposits with hematite cement deposited directly on Salinian granites in the La Panza Range. Paleomagnetic analysis shows two components of magnetization in the red beds, a low-blocking-temperature present-day overprint residing in goethite and a high-blocking-temperature (>600??) component residing in hematite. The hematite magnetization is a chemical remanent magnetization which formed soon after deposition during pedogenesis. The bedding-corrected hematite remanence contains a magnetic polarity stratigraphy with antipodal normal and reversed directions. Twenty-three Class I sites (??95 < 20??) have an average hematite direction with inclination = 54.4?? and declination = 18.2?? (??95 = 6.1??) after structural correction. These paleomagnetic data suggest that Salinia resided at about 35??N latitude during the Late Cretaceous, within 6?? of its current location adjacent to cratonal North America. By contrast, a summary of paleomagnetic data from the Peninsular Ranges terrane and the Sur-Obispo terrane, which are currently outboard of Salinia, shows northward transport of these terranes of 12,.o\\ to 22?? relative to their current locations in North America since the Cretaceous. The offsets increase systematically away from the craton with the most outboard Sur-Obispo terrane (which is composed of accretionary prism and distal forearc material) showing the largest degree of northward translation.
Manuscript Architect: a Web application for scientific writing in virtual interdisciplinary groups
Pietrobon, Ricardo; Nielsen, Karen C; Steele, Susan M; Menezes, Andreia P; Martins, Henrique; Jacobs, Danny O
2005-01-01
Background Although scientific writing plays a central role in the communication of clinical research findings and consumes a significant amount of time from clinical researchers, few Web applications have been designed to systematically improve the writing process. This application had as its main objective the separation of the multiple tasks associated with scientific writing into smaller components. It was also aimed at providing a mechanism where sections of the manuscript (text blocks) could be assigned to different specialists. Manuscript Architect was built using Java language in conjunction with the classic lifecycle development method. The interface was designed for simplicity and economy of movements. Manuscripts are divided into multiple text blocks that can be assigned to different co-authors by the first author. Each text block contains notes to guide co-authors regarding the central focus of each text block, previous examples, and an additional field for translation when the initial text is written in a language different from the one used by the target journal. Usability was evaluated using formal usability tests and field observations. Results The application presented excellent usability and integration with the regular writing habits of experienced researchers. Workshops were developed to train novice researchers, presenting an accelerated learning curve. The application has been used in over 20 different scientific articles and grant proposals. Conclusion The current version of Manuscript Architect has proven to be very useful in the writing of multiple scientific texts, suggesting that virtual writing by interdisciplinary groups is an effective manner of scientific writing when interdisciplinary work is required. PMID:15960855
Zhang, Lei; Liu, Yudan; Chen, Xihua
2005-01-01
Enhanced activity of the central dopamine system has been implicated in many psychiatric disorders including schizophrenia and addiction. Besides terminal mechanisms that boost dopamine levels at the synapse, the cell body of dopamine cells enhances terminal dopamine concentration through encoding action potentials in bursts. This paper presents evidence that burst firing of dopamine cells in the ventral tegmental area was under cholinergic control using nystatin-perforated patch clamp recording from slice preparations. The non-selective cholinergic agonist carbachol excited the majority of recorded neurones, an action that was not affected by blocking glutamate and GABA ionotropic receptors. Twenty per cent of dopamine cells responded to carbachol with robust bursting, an effect mediated by both muscarinic and nicotinic cholinoceptors postsynaptically. Burst firing induced as such was completely dependent on calcium entry as it could be blocked by cadmium and more specifically the L-type blocker nifedipine. In the presence of the sodium channel blocker tetrodotoxin, carbachol induced membrane potential oscillation that had similar kinetics and frequency as burst firing cycles and could also be blocked by cadmium and nifedipine. Direct activation of the L-type channel with Bay K8644 induced strong bursting which could be blocked by nifedipine but not by depleting internal calcium stores. These results indicate that carbachol increases calcium entry into the postsynaptic cell through L-type channels to generate calcium-dependent membrane potential oscillation and burst firing. This could establish the L-type channel as a target for modulating the function of the central dopamine system in disease conditions. PMID:16081481
Kaplowitz, Stan A; Perlstadt, Harry; D'Onofrio, Gail; Melnick, Edward R; Baum, Carl R; Kirrane, Barbara M; Post, Lori A
2012-01-01
We derived a clinical decision rule for determining which young children need testing for lead poisoning. We developed an equation that combines lead exposure self-report questions with the child's census-block housing and socioeconomic characteristics, personal demographic characteristics, and Medicaid status. This equation better predicts elevated blood lead level (EBLL) than one using ZIP code and Medicaid status. A survey regarding potential lead exposure was administered from October 2001 to January 2003 to Michigan parents at pediatric clinics (n=3,396). These self-report survey data were linked to a statewide clinical registry of blood lead level (BLL) tests. Sensitivity and specificity were calculated and then used to estimate the cost-effectiveness of the equation. The census-block group prediction equation explained 18.1% of the variance in BLLs. Replacing block group characteristics with the self-report questions and dichotomized ZIP code risk explained only 12.6% of the variance. Adding three self-report questions to the census-block group model increased the variance explained to 19.9% and increased specificity with no loss in sensitivity in detecting EBLLs of ≥ 10 micrograms per deciliter. Relying solely on self-reports of lead exposure predicted BLL less effectively than the block group model. However, adding three of 13 self-report questions to our clinical decision rule significantly improved prediction of which children require a BLL test. Using the equation as the clinical decision rule would annually eliminate more than 7,200 unnecessary tests in Michigan and save more than $220,000.
Revision of loop colostomy under regional anaesthesia and sedation.
Ng, Oriana; Thong, Sze Ying; Chia, Claramae Shulyn; Teo, Melissa Ching Ching
2015-05-01
Patients presenting for emergency abdominal procedures often have medical issues that cause both general anaesthesia and central neuraxial blockade to pose significant risks. Regional anaesthetic techniques are often used adjunctively for abdominal procedures under general anaesthesia, but there is limited published data on procedures done under peripheral nerve or plexus blocks. We herein report the case of a patient with recent pulmonary embolism and supraventricular tachycardia who required colostomy refashioning. Ultrasonography-guided regional anaesthesia was administered using a combination of ilioinguinal-iliohypogastric, rectus sheath and transversus abdominis plane blocks. This was supplemented with propofol and dexmedetomidine sedation as well as intermittent fentanyl and ketamine boluses to cover for visceral stimulation. We discuss the anatomical rationale for the choice of blocks and compare the anaesthetic conduct with similar cases that were previously reported.
Translations on USSR Resources, Number 763
1978-01-06
supplying gas pumping units, pipes, and other equipment. 33 Shatlyk . Complex Gas Preparation Unit i 1 * Medvezhe. Gas Prepara- tion Block. Thus...handled satisfactorily. . Shatlyk . Turkmengazprom. Central Control Station Combine with Head Facilities Operating Room. By means of the Impul’s-2 remote
Zenner, Hans P; Pfister, Markus; Birbaumer, Niels
2006-12-01
Acquired centralized tinnitus (ACT) is the most frequent form of chronic tinnitus. The proposed ACT sensitization (ACTS) assumes a peripheral initiation of tinnitus whereby sensitizing signals from the auditory system establish new neuronal connections in the brain. Consequently, permanent neurophysiological malfunction within the information-processing modules results. Successful treatment has to target these malfunctioning information processing. We present in this study the neurophysiological and psychophysiological aspects of a recently suggested neurophysiological model, which may explain the symptoms caused by central cognitive tinnitus sensitization. Although conditioned reflexes, as a causal agent of chronic tinnitus, respond to extinction procedures, sensitization may initiate a vicious circle of overexcitation of the auditory system, resisting extinction and habituation. We used the literature database as indicated under "References" covering English and German works. For the ACTS model we extracted neurophysiological hypotheses of the auditory stimulus processing and the neuronal connections of the central auditory system with other brain regions to explain the malfunctions of auditory information processing. The model does not assume information-processing changes specific for tinnitus but treats the processing of tinnitus signals comparable with the processing of other external stimuli. The model uses the extensive knowledge available on sensitization of perception and memory processes and highlights the similarities of tinnitus with central neuropathic pain. Quality, validity, and comparability of the extracted data were evaluated by peer reviewing. Statistical techniques were not used. According to the tinnitus sensitization model, a tinnitus signal originates (as a type I-IV tinnitus) in the cochlea. In the brain, concerned with perception and cognition, the 1) conditioned associations, as postulated by the tinnitus model of Jastreboff, and the 2) unconditioned sensitized stimulus responses, as postulated in the present ACTS model, are actively connected with and attributed to the tinnitus signal. Attention to the tinnitus constitutes a typical undesired sensitized response. Some of the tinnitus-associated attributes may be called essential, unconditioned sensitization attributes. By a process called facilitation, the tinnitus' essential attributes are suggested to activate the tinnitus response. The result is an undesired increase in responsivity, such as an increase in attentional focus to the eliciting tinnitus stimulus. The mechanisms underlying sensitization are known as a specific nonassociative learning process producing a structural fixation of long-term facilitation at the synaptic level. This sensitization model may be important for the development of a sensitization-specific treatment if extinction procedures alone do not lead to satisfactory outcome. Inasmuch as this model considers sensitization as a nonassociative learning process based on cortical plasticity, it is reasonable to assume that this learning process can be altered by counteracting learning procedures. These counteracting learning procedures may consist of tinnitus-specific cognitive and behavioral procedures.
ERIC Educational Resources Information Center
Marchetto, Erika; Bonatti, Luca L.
2015-01-01
To achieve language proficiency, infants must find the building blocks of speech and master the rules governing their legal combinations. However, these problems are linked: words are also built according to rules. Here, we explored early morphosyntactic sensitivity by testing when and how infants could find either words or within-word structure…
Goh, Lucas Y H; Kam, Yiu-Wing; Metz, Stefan W; Hobson-Peters, Jody; Prow, Natalie A; McCarthy, Suzi; Smith, David W; Pijlman, Gorben P; Ng, Lisa F P; Hall, Roy A
2015-09-15
Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans. Copyright © 2015. Published by Elsevier B.V.
O'Leary, L; van der Sloot, A M; Reis, C R; Deegan, S; Ryan, A E; Dhami, S P S; Murillo, L S; Cool, R H; Correa de Sampaio, P; Thompson, K; Murphy, G; Quax, W J; Serrano, L; Samali, A; Szegezdi, E
2016-03-10
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand cytokine known for its cytotoxic activity against malignantly transformed cells. TRAIL induces cell death through binding to death receptors DR4 and DR5. The inhibitory decoy receptors (DcR1 and DcR2) co-expressed with death receptor 4 (DR4)/DR5 on the same cell can block the transmission of the apoptotic signal. Here, we show that DcRs also regulate TRAIL sensitivity at a supracellular level and thus represent a mechanism by which the microenvironment can diminish tumour TRAIL sensitivity. Mathematical modelling and layered or spheroid stroma-extracellular matrix-tumour cultures were used to model the tumour microenvironment. By engineering TRAIL to escape binding by DcRs, we found that DcRs do not only act in a cell-autonomous or cis-regulatory manner, but also exert trans-cellular regulation originating from stromal cells and affect tumour cells, highlighting the potent inhibitory effect of DcRs in the tumour tissue and the necessity of selective targeting of the two death-inducing TRAIL receptors to maximise efficacy.
NASA Astrophysics Data System (ADS)
Gregory, L. C.; Meert, J. G.; Levashova, N.; Grice, W. C.; Gibsher, A.; Rybanin, A.
2007-12-01
The Neoproterozoic to early Paleozoic Ural-Mongol belt that runs through Central Asia is crucial for determining the enigmatic amalgamation of microcontinents that make up the Eurasian subcontinent. Two unique models have been proposed for the evolution of Ural-Mongol belt. One involves a complex assemblage of cratonic blocks that have collided and rifted apart during diachronous opening and closing of Neoproterozoic to Devonian aged ocean basins. The opposing model of Sengor and Natal"in proposes a long-standing volcanic arc system that connected Central Asian blocks with the Baltica continent. The Aktau-Mointy and Dzabkhan microcontinents in Kazakhstan and Central Mongolia make up the central section of the Ural-Mongol belt, and both contain glacial sequences characteristic of the hypothesized snowball earth event. These worldwide glaciations are currently under considerable debate, and paleomagnetic data from these microcontients are a useful contribution to the snowball controversy. We have sampled volcanic and sedimentary sequences in Central Mongolia, Kazakhstan and Kyrgyzstan for paleomagnetic and geochronologic study. U-Pb data, 13C curves and abundant fossil records place age constraints on sequences that contain glacial deposits of the hypothesized snowball earth events. Carbonates in the Zavkhan Basin in Mongolia are likely remagnetized, but fossil evidence within the sequence suggests a readjusted age control on two glacial events that were previously labeled as Sturtian and Marinoan. U-Pb ages from both Kazakhstan and Mongolian volcanic sequences imply a similar evolution history of the areas as part of the Ural-Mongol fold belt, and these ages paired with paleomagnetic and 13C records have important tectonic implications. We will present these data in order to place better constraints on the Precambrian to early Paleozoic tectonic evolution of Central Asia and the timing of glacial events recorded in the area.
Predicting successful supraclavicular brachial plexus block using pulse oximeter perfusion index.
Abdelnasser, A; Abdelhamid, B; Elsonbaty, A; Hasanin, A; Rady, A
2017-08-01
Supraclavicular nerve block is a popular approach for anaesthesia for upper limb surgeries. Conventional methods for evaluation of block success are time consuming and need patient cooperation. The aim of this study was to evaluate whether the perfusion index (PI) can be used to predict and provide a cut-off value for ultrasound-guided supraclavicular nerve block success. The study included 77 patients undergoing elective orthopaedic procedures under ultrasound-guided supraclavicular nerve block. After local anaesthetic injection, sensory block success was assessed every 3 min by pinprick, and motor block success was assessed every 5 min by the ability to flex the elbow and the hand against resistance. The PI was recorded at baseline and at 10, 20, and 30 min after anaesthetic injection in both blocked and non-blocked limbs. The PI ratio was calculated as the PI after 10 min divided by the PI at the baseline. Receiver operating characteristic curves were constructed for the accuracy of the PI in detection of block success. The PI was higher in the blocked limb at all time points, and this was paralleled by a higher PI ratio compared with the unblocked limb. Both the PI and the PI ratio at 10 min after injection showed a sensitivity and specificity of 100% for block success at cut-off values of 3.3 and 1.4, respectively. The PI is a useful tool for evaluation of successful supraclavicular nerve block. A PI ratio of > 1.4 is a good predictor for block success. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com
... 1. In some patients with discoid lupus erythematosus, sunlight and cigarette smoking may make the lesions come ... be used. Patients whose condition is sensitive to sunlight need to wear a UVA/UVB blocking sunscreen ...
NASA Astrophysics Data System (ADS)
Sweeney, J. K.; Chagnon, J. M.; Gray, S. L.
2014-05-01
The sensitivity of sea breeze structure to sea surface temperature (SST) and coastal orography is investigated in convection-permitting Met Office Unified Model simulations of a case study along the south coast of England. Changes in SST of 1 K are shown to significantly modify the structure of the sea breeze immediately offshore. On the day of the case study, the sea breeze was partially blocked by coastal orography, particularly within Lyme Bay. The extent to which the flow is blocked depends strongly on the static stability of the marine boundary layer. In experiments with colder SST, the marine boundary layer is more stable, and the degree of blocking is more pronounced. Although a colder SST would also imply a larger land-sea temperature contrast and hence a stronger onshore wind - an effect which alone would discourage blocking - the increased static stability exerts a dominant control over whether blocking takes place. The implications of prescribing fixed SST from climatology in numerical weather prediction model forecasts of the sea breeze are discussed.
NASA Astrophysics Data System (ADS)
Barman, Prakash; Jade, Sridevi; Shrungeshwara, T. S.; Kumar, Ashok; Bhattacharyya, Sanjeev; Ray, Jagat Dwipendra; Jagannathan, Saigeetha; Jamir, Wangshi Menla
2017-09-01
The present study reports the contemporary deformation of the tectonically complex northeast India using 11 years (2002-2013) of GPS observations. The central Shillong Plateau and few sites north of Plateau located in Assam Valley behave like a rigid block with 7 mm/year India-fixed southward velocity. The Euler pole of rotation of this central Shillong Plateau-Assam Valley (SH-AS) block is estimated to be at -25.1° ± 0.2°N, -97.8° ± 1.8°E with an angular velocity of 0.533° ± 0.10° Myr-1 relative to India-fixed reference frame. Kopili fault located between Shillong Plateau and Mikir massif records a dextral slip of 4.7 ± 1.3 mm/year with a locking depth of 10.2 ± 1.4 km indicating the fragmentation of Assam Valley across the fault. Presently, western edge of Mikir massif appears to be locked to Assam block indicating strain accumulation in this region. First-order elastic dislocation modelling of the GPS velocities estimates a slip rate of 16 mm/year along the Main Himalayan Thrust in Eastern Himalaya which is locked over a width of 130 km from the surface to a depth of 17 km with underthrusting Indian plate. Around 9 mm/year arc-normal convergence is accommodated in Lesser Himalaya just south of Main Central Thrust indicating high strain accumulation. Out of 36 mm/year (SSE) India-Sunda plate motion, about 16 mm/year motion is accommodated in Indo-Burmese Fold and Thrust Belt, both as normal convergence ( 6 mm/year) and active slip ( 7-11 mm/year) in this region.
NASA Astrophysics Data System (ADS)
Cao, J.; Xia, S.; Sun, J.; Wan, K.; Xu, H.
2017-12-01
Known as a significant region to study tectonic relationship between South China block and South China Sea (SCS) block and the evolution of rifted basin in continental margin, the continental shelf of northern SCS documents the evolution from continental splitting to seafloor spreading of SCS. To investigate crustal structure of central continental shelf in northern SCS, two wide-angle onshore-offshore seismic experiments and coincident multi-channel seismic (MCS) profiles were carried out across the onshore-offshore transitional zone in northern SCS, 2010 and 2012. A total of 34 stations consisted of ocean bottom seismometers, portable and permanent land stations were deployed during the survey. The two-dimensional precise crustal structure models of central continental shelf in northern SCS was constructed from onshore to offshore, and the stretching factors along the P-wave velocity models were calculated. The models reveal that South China block is a typical continental crust with a 30-32 km Moho depth, and a localized high-velocity anomaly in middle-lower crust under land area near Hong Kong was imaged, which may reflect magma underplating caused by subduction of paleo-Pacific plate in late Mesozoic. The littoral fault zone is composed of several parallel, high-angle, normal faults that mainly trend northeast to northeast-to-east and dip to the southeast with a large displacement, and the fault is divided into several segments separated by the northwest-trending faults. The shelf zone south of LFZ was consisted of a differential thinning upper and lower continental crust, which indicate stretch thinning of passive continent margin during the Cenozoic spreading of the SCS. The results appear to further confirm that the northern margin of SCS experienced a transition from active margin to passive one during late Mesozoic and Cenozoic.
Milner, Rafał; Lewandowska, Monika; Ganc, Małgorzata; Włodarczyk, Elżbieta; Grudzień, Diana; Skarżyński, Henryk
2018-01-01
In this study, we showed an abnormal resting-state quantitative electroencephalogram (QEEG) pattern in children with central auditory processing disorder (CAPD). Twenty-seven children (16 male, 11 female; mean age = 10.7 years) with CAPD and no symptoms of other developmental disorders, as well as 23 age- and sex-matched, typically developing children (TDC, 11 male, 13 female; mean age = 11.8 years) underwent examination of central auditory processes (CAPs) and QEEG evaluation consisting of two randomly presented blocks of “Eyes Open” (EO) or “Eyes Closed” (EC) recordings. Significant correlations between individual frequency band powers and CAP tests performance were found. The QEEG studies revealed that in CAPD relative to TDC there was no effect of decreased delta absolute power (1.5–4 Hz) in EO compared to the EC condition. Furthermore, children with CAPD showed increased theta power (4–8 Hz) in the frontal area, a tendency toward elevated theta power in EO block, and reduced low-frequency beta power (12–15 Hz) in the bilateral occipital and the left temporo-occipital regions for both EO and EC conditions. Decreased middle-frequency beta power (15–18 Hz) in children with CAPD was observed only in the EC block. The findings of the present study suggest that QEEG could be an adequate tool to discriminate children with CAPD from normally developing children. Correlation analysis shows relationship between the individual EEG resting frequency bands and the CAPs. Increased power of slow waves and decreased power of fast rhythms could indicate abnormal functioning (hypoarousal of the cortex and/or an immaturity) of brain areas not specialized in auditory information processing.
Environmental impact of melting buried ice blocks (North Poland)
NASA Astrophysics Data System (ADS)
Ott, F.; Slowinski, M. M.; Blaszkiewicz, M.; Brauer, A.; Noryskiewicz, B.; Tyszkowski, S.
2013-12-01
The aim of the research was to decipher the impacts of the role of dead ice melting on landscape evolution in the Lateglacial and early Holocene Central Europe. Here, we present the paleoecological results from the middle section of the Wda river which is located in northern Poland (Central Europe), on the outwash plain formed during the Pomeranian phase of the last (Vistulian) glacial period ca 16,000 14C yrs BP. The Wda river has a typical polygenetic valley in young glacial areas of the northern central European lowlands. We reconstructed environmental changes using biotic proxies (plant macrofossil and pollen analyses) and geomorphological investigations. In this study we focused on a short terrestrial sediment core (48 cm) representing four phases of landscape evolution: telmatic, lacustrine, lacustrine-fluvial and alluvial. Abrupt changes in lithology and sediment structures show rapid changes and threshold processes in environmental conditions. The AMS 14C dating of terrestrial plant remains reveals an age for the basal sediments of 11 223 × 23 cal yr BP and thus falls within the Preboreal biozone. Our results showed that existence of buried ice blocks in northern Poland even at the beginning of the Holocene is clear evidence that locally discontinuous permafrost still was present at that time. The results of our study prove a strong influence of melting buried ice blocks on the geomorphological development, hydrological changes in the catchment, and the biotic environment even in the early Holocene. The research was supported by the National Science Centre Poland (grants No. NN 306085037 and NCN 2011/01/B/ST10/07367). This study is a contribution to the Virtual Institute of Integrated Climate and Landscape Evolution (ICLEA) of the Helmholtz Association. Financial support by the COST Action ES0907 INTIMATE is gratefully acknowledged.
Preservation of adobe buildings. Study of materials
NASA Astrophysics Data System (ADS)
Velosa, A.; Rocha, F.; Costa, C.; Varum, H.
2012-04-01
Adobe buildings are common in the central region of Portugal due to the lack of natural stone in the surrounding area. This type of construction technique lasted until the 20th Century, at which time cementitious materials, with faster hardening and greater structural capacity substituted traditional materials and techniques. Currently, a significant percentage of these buildings is vacant and many are degraded and in need of conservation actions. Adobes from central Portugal are distinctive as they are lightly coloured and made from air lime and quarry sand. Although some adobes were manufactured locally, most were produced almost 'industrially' and sold to nearby regions. In order to preserve this heritage, conservation actions must be undertaken. So as to ensure the adequacy of these actions and compatibility between original materials and new ones, a thorough study of adobe compostion is mandatory. The current study is an initial step in the characterization of earth based construction materials from central Portugal. Adobe samples were collected from residential buildings in two different locations. The determination of the composition of adobe blocks encompassed the determination of the binder fraction and of their chemical composition and also the particle size analysis of the aggregate. For this purpose FRX analysis, acid dissolution and dry sieving were performed. Methylene blue test was also executed in order to determine the clay fraction. Additionally, the mineral composition of powder samples and oriented samples was performed using XRD analysis in order to determine the clay minerals present in the blocks. As adobe blocks are extremely prone to the action of water the Geelong test was undertaken in order to provide information in terms of durability. It was concluded that air lime was generally used in adobe compositions. However, the clay content varies in adobes from different regions, providing distinct durability characteristics to these materials.
Acute dyskinetic reaction in a healthy toddler following methylphenidate ingestion.
Waugh, Jeff L
2013-07-01
Acute dyskinetic or dystonic reactions are a long-recognized complication of medications that alter dopamine signaling. Most reactions occur following exposure to agents that block dopamine receptors (e.g., neuroleptics). However, agents that increase dopaminergic transmission (such as methylphenidate) can also trigger acute dyskinesias. This has been previously reported only in patients also taking dopamine antagonists or, less commonly, in children with developmental abnormalities. The present report describes a previously healthy toddler who developed transient torticollis and orolingual dyskinesias following accidental exposure to methylphenidate. He had no preexisting movement disorder, central nervous system injury, or developmental abnormalities--in short, none of the previously reported risk factors for this side effect. The unique features of this case led to the hypothesis that developmental shifts in dopamine signaling were the basis for his particular sensitivity to methylphenidate. If confirmed, this hypothesis has implications for the treatment of common childhood attentional and behavioral disorders. The article includes a literature review of dyskinetic/dystonic reactions in children and the developmental regulation of dopamine metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.
Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.
Czapla, Marc A; Zadina, James E
2005-10-19
Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. Minute ventilation (V(E)) in 2, 4, and 6% CO(2) was measured before and after systemic administration of EM1, endomorphin-2 (EM2), DAMGO, and morphine in the conscious rat. EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.
Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures
Palanca, José M.; Aguirre-Rueda, Diana; Granell, Manuel V.; Aldasoro, Martin; Garcia, Alma; Iradi, Antonio; Obrador, Elena; Mauricio, Maria Dolores; Vila, Jose; Gil-Bisquert, Anna; Valles, Soraya L.
2013-01-01
Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system). Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types. PMID:23983586
Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings
Passmore, Gayle M.; Reilly, Joanne M.; Thakur, Matthew; Keasberry, Vanessa N.; Marsh, Stephen J.; Dickenson, Anthony H.; Brown, David A.
2012-01-01
M-channels carry slowly activating potassium currents that regulate excitability in a variety of central and peripheral neurons. Functional M-channels and their Kv7 channel correlates are expressed throughout the somatosensory nervous system where they may play an important role in controlling sensory nerve activity. Here we show that Kv7.2 immunoreactivity is expressed in the peripheral terminals of nociceptive primary afferents. Electrophysiological recordings from single afferents in vitro showed that block of M-channels by 3 μM XE991 sensitized Aδ- but not C-fibers to noxious heat stimulation and induced spontaneous, ongoing activity at 32°C in many Aδ-fibers. These observations were extended in vivo: intraplantar injection of XE991 selectively enhanced the response of deep dorsal horn (DH) neurons to peripheral mid-range mechanical and higher range thermal stimuli, consistent with a selective effect on Aδ-fiber peripheral terminals. These results demonstrate an important physiological role of M-channels in controlling nociceptive Aδ-fiber responses and provide a rationale for the nocifensive behaviors that arise following intraplantar injection of the M-channel blocker XE991. PMID:22593734
Besedin, V I; Kuznetsov, A S; Dambinova, S A
1985-03-01
The functioning of the glutamate-binding protein of rat brain cortex synaptic membranes was studied by its incorporation into liposomes. The optimal conditions for the receptor protein incorporation were established and the kinetics of 22Na+ and 86Rb+ incorporation into the liposomes in the presence of L-glutamate were analyzed. Modelling of the CNS glutamate receptor functions was found to be dependent on the lipid composition and amount of the incorporated membrane protein. The selective transport of 22Na+ into the liposomes was stimulated in the presence of 10(-4) M glutamate. Addition of monoclonal antibodies against glutamate-binding proteins blocked the incorporation of Na+ into the liposomes. The experimental results are suggestive of the nativity of the liposome-incorporated membrane protein, which is capable of binding glutamate and regulating selective transport of Na+. It was assumed that the glutamate receptor macromolecule represents an integral complex made up of several low molecular weight subunits of glucoprotein nature that form a selective ionic channel.
2014-09-01
rod moves about the illumination scene, the pixels in the detector start to flicker . The ‘ flickering ’ effect is due to the metal rod blocking THz...still possible to mitigate convective heat exchange between the sensor and the ambient surroundings. To mitigate the effects of convective heat...detector start to flicker . The ‘ flickering ’ effect is due to the metal rod blocking THz radiation. This effect is more apparent in the video
Zhang, Ying; Zhan, Tian-Guang; Zhou, Tian-You; Qi, Qiao-Yan; Xu, Xiao-Na; Zhao, Xin
2016-06-18
A two-dimensional (2D) supramolecular organic framework (SOF) has been constructed through the co-assembly of a triphenylamine-based building block and cucurbit[8]uril (CB[8]). Fluorescence turn-on of the non-emissive building block was observed upon the formation of the 2D SOF, which displayed highly selective and sensitive recognition of picric acid over a variety of nitroaromatics.
2013-01-01
High performance is expected in dye-sensitized solar cells (DSSCs) that utilize one-dimensional (1-D) TiO2 nanostructures owing to the effective electron transport. However, due to the low dye adsorption, mainly because of their smooth surfaces, 1-D TiO2 DSSCs show relatively lower efficiencies than nanoparticle-based ones. Herein, we demonstrate a very simple approach using thick TiO2 electrospun nanofiber films as photoanodes to obtain high conversion efficiency. To improve the performance of the DSCCs, anatase-rutile mixed-phase TiO2 nanofibers are achieved by increasing sintering temperature above 500°C, and very thin ZnO films are deposited by atomic layer deposition (ALD) method as blocking layers. With approximately 40-μm-thick mixed-phase (approximately 15.6 wt.% rutile) TiO2 nanofiber as photoanode and 15-nm-thick compact ZnO film as a blocking layer in DSSC, the photoelectric conversion efficiency and short-circuit current are measured as 8.01% and 17.3 mA cm−2, respectively. Intensity-modulated photocurrent spectroscopy and intensity-modulated photovoltage spectroscopy measurements reveal that extremely large electron diffusion length is the key point to support the usage of thick TiO2 nanofibers as photoanodes with very thin ZnO blocking layers to obtain high photocurrents and high conversion efficiencies. PMID:23286741
Pulkkinen, Mika; Malin, Minna; Tarvainen, Tommy; Saarimäki, Tiina; Seppälä, Jukka; Järvinen, Kristiina
2007-06-01
The aim of the study was to develop enzyme sensitive polymers for pharmaceutical applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O) polymers were synthesized by using epsilon-caprolactone precursors with different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the effects of PCL block length on enzymatic degradation and erosion (weight loss) of PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22 days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O films occurred during incubation, and the erosion of the PCL-O films increased in parallel with a decrease in the PCL block length. The presence of the lipase inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the PCL-O films. These results indicate that lipase was mainly responsible for the enzymatic erosion of the PCL-O films. In comparison, practically no weight loss of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days incubation). The results demonstrate that the studied epsilon-caprolactone based poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be controlled by the PCL block length.
NASA Astrophysics Data System (ADS)
Sweeney, J. K.; Chagnon, J. M.; Gray, S. L.
2013-09-01
The sensitivity of sea breeze structure to sea surface temperature (SST) and coastal orography is investigated in convection-permitting Met Office Unified Model simulations of a case study along the south coast of England. Changes in SST of 1 K are shown to significantly modify the structure of the sea breeze. On the day of the case study the sea breeze was partially blocked by coastal orography, particularly within Lyme Bay. The extent to which the flow is blocked depends strongly on the static stability of the marine boundary layer. In experiments with colder SST, the marine boundary layer is more stable, and the degree of blocking is more pronounced. The implications of prescribing fixed SST from climatology in numerical weather prediction model forecasts of the sea breeze are discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Connor, Jason M.; McLellan, Jason G.; O'Connor, Dick
In 1980, the United States Congress enacted the Northwest Power Planning and Conservation Act (PL 96-501, 1980), which established the Northwest Power Planning Council (NPPC). The NPPC was directed by Congress to develop a regional Power Plan and also the Columbia River Basin Fish and Wildlife Program (FWP) to restore or replace losses of fish caused by construction and operation of hydroelectric dams in the Columbia River Basin. In developing the FWP, Congress specifically directed NPPC to solicit recommendations for measures to be included in the Program from the region's fish and wildlife agencies and Indian tribes. All measures adoptedmore » by the Council were also required to be consistent with the management objectives of the agencies and tribes [Section 4.(h)(6)(A)], the legal rights of Indian tribes in the region [Section 4.(h)(6)(D)] and be based upon and supported by the best available scientific knowledge [Section 4.(h)(6)(B)]. The Resident Fish Stock Status above Chief Joseph and Grand Coulee Dams Project, also known as the Joint Stock Assessment Project (JSAP) specifically addresses NPPC Council measure 10.8B.26 of the 1994 program. The Joint Stock Assessment Project is a management tool using ecosystem principles to manage artificial fish assemblages and native fish in altered environments existing in the Columbia River System above Chief Joseph and Grand Coulee Dams (Blocked Area). A three-phase approach of this project will enhance the fisheries resources of the Blocked Area by identifying data gaps, filling data gaps with research, and implementing management recommendations based on research results. The Blocked Area fisheries information is housed in a central location, allowing managers to view the entire system while making decisions, rather than basing management decisions on isolated portions of the system. The JSAP is designed and guided jointly by fisheries managers in the Blocked Area and the Columbia Basin Blocked Area Management Plan (1998). The initial year of the project (1997) identified the need for a central data storage and analysis facility, coordination with the StreamNet project, compilation of Blocked Area fisheries information, and a report on the ecological condition of the Spokane River System. These needs were addressed in 1998 by acquiring a central location with a data storage and analysis system, coordinating a pilot project with StreamNet, compiling fisheries distribution data throughout the Blocked Area, identifying data gaps based on compiled information, and researching the ecological condition of the Spokane River. In order to ensure that any additional information collected throughout the life of this project will be easily stored and manipulated by the central storage facility, it was necessary to develop standardized methodologies between the JSAP fisheries managers. Common collection and analytical methodologies were developed in 1999. In 1999, 2000, and 2001 the project began addressing some of the identified data gaps throughout the Blocked Area. Data collection of established projects and a variety of newly developed sampling projects are ongoing. Projects developed and undertaken by JSAP fisheries managers include investigations of the Pend Orielle River and its tributaries, the Little Spokane River and its tributaries, and water bodies within and near the Spokane Indian Reservation. Migration patterns of adfluvial and reservoir fish in Box Canyon Reservoir and its tributaries, a baseline assessment of Boundary Reservoir and its tributaries, ecological assessment of mountain lakes in Pend Oreille County, and assessments of seven streams and four lakes on the Spokane Indian Reservation were completed by 2000. Assessments of the Little Spokane River and its tributaries, tributaries to the Pend Oreille River, small lakes in southern Pend Oreille County, and water bodies within and near the Spokane Indian Reservation were conducted in 2001. This work was done in accordance with the scope of work approved by Bonneville Power Administration (BPA).« less
Copolymerization of Glycolide and ɛ-Caprolactone Using 12-Aminolauric Acid Modified Montmorillonite
NASA Astrophysics Data System (ADS)
Gallos, HAV; Reyes, LQ
2017-09-01
Poly(glycolide-co-ɛ-caprolactone) (PGLYCL) nanocomposites were prepared by copolymerization glycolide (GLY) and ɛ-caprolactone (ɛ-CL) in the presence of varying loadings 12-aminolauric acid (12-ALA)-modified montmorillonite. Copolymerization was successfully achieved based on the increase in polymer molecular weight after the reaction determined by gel permeation chromatography (GPC). The amount of the poly(glycolide) block and poly(ɛ-caprolactone) block units in the copolymer, identified by proton nuclear magnetic resonance (1H-NMR) spectroscopy, suggested that the increase in organo-clay loading cause a reduction GLYL: ɛ-CLL ratio. The arrangement of the monomers in the polymer products was elucidated to have an ABA triblock structure, where PCL block is the central block and the PGLY is found at both end of the copolymer. The presence of intercalated and exfoliated silicates in the nanocomposites were observed by x-ray diffraction (XRD) analysis. The biocompatibility of the nanocomposites with NCTC 292 mouse normal fibroblast was high relative to untreated cell cultures using tetrazolium bromide (MTT)-dye reduction assay.
A comparison between block and smooth modeling in finite element simulations of tDCS*
Indahlastari, Aprinda; Sadleir, Rosalind J.
2018-01-01
Current density distributions in five selected structures, namely, anterior superior temporal gyrus (ASTG), hippocampus (HIP), inferior frontal gyrus (IFG), occipital lobe (OCC) and pre-central gyrus (PRC) were investigated as part of a comparison between electrostatic finite element models constructed directly from MRI-resolution data (block models), and smoothed tetrahedral finite element models (smooth models). Three electrode configurations were applied, mimicking different tDCS therapies. Smooth model simulations were found to require three times longer to complete. The percentage differences between mean and median current densities of each model type in arbitrarily chosen brain structures ranged from −33.33–48.08%. No clear relationship was found between structure volumes and current density differences between the two model types. Tissue regions nearby the electrodes demonstrated the least percentage differences between block and smooth models. Therefore, block models may be adequate to predict current density values in cortical regions presumed targeted by tDCS. PMID:26737023
Yao, Yuan; Shen, Heyun; Zhang, Guanghui; Yang, Jing; Jin, Xu
2014-10-01
We introduced thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) into the polymer structure of poly(ethylene glycol)-block-poly(phenylboronate ester) acrylate (MPEG-block-PPBDEMA) by block and random polymerization pathways in order to investigate the effect of polymer architecture on the glucose-responsiveness and enhance their insulin release controllability. By following the structure, the continuous PNIPAM shell of the triblock polymer MPEG-block-PNIPAM-block-PPBDEMA collapsing on the glucose-responsive PPBDEMA core formed the polymeric micelles with a core-shell-corona structure, and MPEG-block-(PNIPAM-rand-PPBDEMA) exhibited core-corona micelles in which the hydrophobic core consisted of PNIPAM and PPBDEMA segments when the environmental temperature was increased above low critical solution temperature (LCST) of PNIPAM. The micellar morphologies can be precisely controlled by temperature change between 15 and 37°C. As a result, the introduction of PNIPAM greatly enhanced the overall stability of insulin encapsulated in the polymeric micelles in the absence of glucose over incubation 80 h at 37°C. Comparing to MPEG-block-PNIPAM-block-PPBDEMA, the nanocarriers from MPEG-block-(PNIPAM-rand-PPBDEMA) showed great insulin release behavior which is zero insulin release without glucose, low release at normal blood glucose concentration (1.0 mg/mL). Therefore, these nanocarriers may be served as promising self-regulated insulin delivery system for diabetes treatment. Copyright © 2014 Elsevier Inc. All rights reserved.
Sun, Yung-Shin; Zhu, Xiangdong
2016-10-01
Microarrays provide a platform for high-throughput characterization of biomolecular interactions. To increase the sensitivity and specificity of microarrays, surface blocking is required to minimize the nonspecific interactions between analytes and unprinted yet functionalized surfaces. To block amine- or epoxy-functionalized substrates, bovine serum albumin (BSA) is one of the most commonly used blocking reagents because it is cheap and easy to use. Based on standard protocols from microarray manufactories, a BSA concentration of 1% (10 mg/mL or 200 μM) and reaction time of at least 30 min are required to efficiently block epoxy-coated slides. In this paper, we used both fluorescent and label-free methods to characterize the BSA blocking efficiency on epoxy-functionalized substrates. The blocking efficiency of BSA was characterized using a fluorescent scanner and a label-free oblique-incidence reflectivity difference (OI-RD) microscope. We found that (1) a BSA concentration of 0.05% (0.5 mg/mL or 10 μM) could give a blocking efficiency of 98%, and (2) the BSA blocking step took only about 5 min to be complete. Also, from real-time and in situ measurements, we were able to calculate the conformational properties (thickness, mass density, and number density) of BSA molecules deposited on the epoxy surface. © 2015 Society for Laboratory Automation and Screening.
Cuevas, Javier; Roth, Adelheid L; Berg, Darwin K
2000-01-01
Nicotinic acetylcholine receptors (nAChRs) that bind α-bungarotoxin (αBgt) were studied on isolated rat superior cervical ganglion (SCG) neurons using whole-cell patch clamp recording techniques.Rapid application of ACh onto the soma of voltage clamped neurons evoked a slowly desensitizing current that was reversibly blocked by αBgt (50 nm). The toxin-sensitive current constituted on average about half of the peak whole-cell response evoked by ACh.Nanomolar concentrations of methyllycaconitine blocked the αBgt-sensitive component of the ACh-evoked current as did intracellular dialysis with an anti-α7 monoclonal antibody. The results indicate that the slowly reversible toxin-sensitive response elicited by ACh arises from activation of an unusual class of α7-containing receptor (α7-nAChR) similar to that reported previously for rat intracardiac ganglion neurons.A second class of functional α7-nAChR was identified on some SCG neurons by using rapid application of choline to elicit responses. In these cases a biphasic response was obtained, which included a rapidly desensitizing component that was blocked by αBgt in a pseudo-irreversible manner. The pharmacology and kinetics of the responses resembled those previously attributed to α7-nAChRs in a number of other neuronal cell types.Experiments measuring the dissociation rate of 125I-labelled αBgt from SCG neurons revealed two classes of toxin-binding site. The times for toxin dissociation were consistent with those required to reverse blockade of the two kinds of αBgt-sensitive response.These results indicate that rat SCG neurons express two types of functional α7-nAChR, differing in pharmacology, desensitization and reversibility of αBgt blockade. PMID:10856125
Sampling Methods for Detection and Monitoring of the Asian Citrus Psyllid (Hemiptera: Psyllidae).
Monzo, C; Arevalo, H A; Jones, M M; Vanaclocha, P; Croxton, S D; Qureshi, J A; Stansly, P A
2015-06-01
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama is a key pest of citrus due to its role as vector of citrus greening disease or "huanglongbing." ACP monitoring is considered an indispensable tool for management of vector and disease. In the present study, datasets collected between 2009 and 2013 from 245 citrus blocks were used to evaluate precision, sensitivity for detection, and efficiency of five sampling methods. The number of samples needed to reach a 0.25 standard error-mean ratio was estimated using Taylor's power law and used to compare precision among sampling methods. Comparison of detection sensitivity and time expenditure (cost) between stem-tap and other sampling methodologies conducted consecutively at the same location were also assessed. Stem-tap sampling was the most efficient sampling method when ACP densities were moderate to high and served as the basis for comparison with all other methods. Protocols that grouped trees near randomly selected locations across the block were more efficient than sampling trees at random across the block. Sweep net sampling was similar to stem-taps in number of captures per sampled unit, but less precise at any ACP density. Yellow sticky traps were 14 times more sensitive than stem-taps but much more time consuming and thus less efficient except at very low population densities. Visual sampling was efficient for detecting and monitoring ACP at low densities. Suction sampling was time consuming and taxing but the most sensitive of all methods for detection of sparse populations. This information can be used to optimize ACP monitoring efforts. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.
Alsanea, Sary; Gao, Mingming; Liu, Dexi
2017-05-01
Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.
A multi-directional tracer test in the fractured Chalk aquifer of E. Yorkshire, UK.
Hartmann, S; Odling, N E; West, L J
2007-12-07
A multi-borehole radial tracer test has been conducted in the confined Chalk aquifer of E. Yorkshire, UK. Three different tracer dyes were injected into three injection boreholes and a central borehole, 25 m from the injection boreholes, was pumped at 330 m(3)/d for 8 days. The breakthrough curves show that initial breakthrough and peak times were fairly similar for all dyes but that recoveries varied markedly from 9 to 57%. The breakthrough curves show a steep rise to a peak and long tail, typical of dual porosity aquifers. The breakthrough curves were simulated using a 1D dual porosity model. Model input parameters were constrained to acceptable ranges determined from estimations of matrix porosity and diffusion coefficient, fracture spacing, initial breakthrough times and bulk transmissivity of the aquifer. The model gave equivalent hydraulic apertures for fractures in the range 363-384 microm, dispersivities of 1 to 5 m and matrix block sizes of 6 to 9 cm. Modelling suggests that matrix block size is the primary controlling parameter for solute transport in the aquifer, particularly for recovery. The observed breakthrough curves suggest results from single injection-borehole tracer tests in the Chalk may give initial breakthrough and peak times reasonably representative of the aquifer but that recovery is highly variable and sensitive to injection and abstraction borehole location. Consideration of aquifer heterogeneity suggests that high recoveries may be indicative of a high flow pathway adjacent, but not necessarily connected, to the injection and abstraction boreholes whereas low recoveries may indicate more distributed flow through many fractures of similar aperture.
NASA Astrophysics Data System (ADS)
Dubinin, Evgeny; Grokholsky, Andrey; Makushkina, Anna
2016-04-01
Complex process of continental lithosphere breakup is often accompanied by full or semi isolation of small continental blocks from the parent continent such as microcontinents or submerged marginal plateaus. We present different types of continental blocks formed in various geodynamic settings. The process depends on thermo-mechanical properties of rifting. 1) The continental blocks fully isolated from the parent continent. This kind of blocks exist in submerged form (Elan Bank, the Jan-Mayen Ridge, Zenith Plateau, Gulden Draak Knoll, Batavia Knoll) and in non-submerged form in case of large block size. Most of listed submerged blocks are formed in proximity of hot-spot or plume. 2) The continental blocks semi-isolated from the parent continent. Exmouth Plateau, Vøring, Agulhas, Naturaliste are submerged continental plateaus of the indicated category; Sri Lanka, Tasmania, Socotra are islands adjacent to continent here. Nowadays illustration of this setting is the Sinai block located between the two continental rifts. 3) The submerged linear continental blocks formed by the continental rifting along margin (the Lomonosov Ridge). Suggested evolution of this paragraph is the rift propagation along existing transtensional (or another type) transform fault. Future example of this type might be the California Peninsula block, detached from the North American plate by the rifting within San-Andreas fault. 4) The submerged continental blocks formed by extensional processes as the result of asthenosphere flow and shear deformations. Examples are submerged blocks in the central and southern Scotia Sea (Terror Bank, Protector Basin, Discovery Bank, Bruce Bank etc.). 5) The continental blocks formed in the transform fault systems originated in setting of contradict rifts propagation in presence of structure barriers, rifts are shifted by several hundreds kilometers from each other. Examples of this geodynamic setting are Equatorial Atlantic at the initial development stage, and the transitional zone between Mohns and Gakkel Ridges. The research funded by RFBR, project № 15-05-03486.
Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen
2018-01-01
The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.
Mannangatti, Padmanabhan; NarasimhaNaidu, Kamalakkannan; Damaj, Mohamad Imad; Ramamoorthy, Sammanda; Jayanthi, Lankupalle Damodara
2015-01-01
The noradrenergic and p38 mitogen-activated protein kinase (p38 MAPK) systems are implicated in cocaine-elicited behaviors. Previously, we demonstrated a role for p38 MAPK-mediated norepinephrine transporter (NET) Thr30 phosphorylation in cocaine-induced NET up-regulation (Mannangatti, P., Arapulisamy, O., Shippenberg, T. S., Ramamoorthy, S., and Jayanthi, L. D. (2011) J. Biol. Chem. 286, 20239–20250). The present study explored the functional interaction between p38 MAPK-mediated NET regulation and cocaine-induced behaviors. In vitro cocaine treatment of mouse prefrontal cortex synaptosomes resulted in enhanced NET function, surface expression, and phosphorylation. Pretreatment with PD169316, a p38 MAPK inhibitor, completely blocked cocaine-mediated NET up-regulation and phosphorylation. In mice, in vivo administration of p38 MAPK inhibitor SB203580 completely blocked cocaine-induced NET up-regulation and p38 MAPK activation in the prefrontal cortex and nucleus accumbens. When tested for cocaine-induced locomotor sensitization and conditioned place preference (CPP), mice receiving SB203580 on cocaine challenge day or on postconditioning test day exhibited significantly reduced cocaine sensitization and CPP. A transactivator of transcription (TAT) peptide strategy was utilized to test the involvement of the NET-Thr30 motif. In vitro treatment of synaptosomes with TAT-NET-Thr30 (wild-type peptide) completely blocked cocaine-mediated NET up-regulation and phosphorylation. In vivo administration of TAT-NET-Thr30 peptide but not TAT-NET-T30A (mutant peptide) completely blocked cocaine-mediated NET up-regulation and phosphorylation. In the cocaine CPP paradigm, mice receiving TAT-NET-Thr30 but not TAT-NET-T30A on postconditioning test day exhibited significantly reduced cocaine CPP. Following extinction, TAT-NET-Thr30 when given prior to cocaine challenge significantly reduced reinstatement of cocaine CPP. These results demonstrate that the direct inhibition of p38 MAPK or the manipulation of NET-Thr30 motif/phosphorylation via a TAT peptide strategy prevents cocaine-induced NET up-regulation, locomotor sensitization, and CPP, suggesting a role for Thr30-linked NET regulation in cocaine-elicited behaviors. PMID:25724654
MedBlock: Efficient and Secure Medical Data Sharing Via Blockchain.
Fan, Kai; Wang, Shangyang; Ren, Yanhui; Li, Hui; Yang, Yintang
2018-06-21
With the development of electronic information technology, electronic medical records (EMRs) have been a common way to store the patients' data in hospitals. They are stored in different hospitals' databases, even for the same patient. Therefore, it is difficult to construct a summarized EMR for one patient from multiple hospital databases due to the security and privacy concerns. Meanwhile, current EMRs systems lack a standard data management and sharing policy, making it difficult for pharmaceutical scientists to develop precise medicines based on data obtained under different policies. To solve the above problems, we proposed a blockchain-based information management system, MedBlock, to handle patients' information. In this scheme, the distributed ledger of MedBlock allows the efficient EMRs access and EMRs retrieval. The improved consensus mechanism achieves consensus of EMRs without large energy consumption and network congestion. In addition, MedBlock also exhibits high information security combining the customized access control protocols and symmetric cryptography. MedBlock can play an important role in the sensitive medical information sharing.
Kim, Ji Eun; Chun, Hea Rim
2017-01-01
Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578
Kim, Ji Eun; Chun, Hea Rim
2017-03-01
Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.
Blocking Filters with Enhanced Throughput for X-Ray Microcalorimetry
NASA Technical Reports Server (NTRS)
Grove, David; Betcher, Jacob; Hagen, Mark
2012-01-01
New and improved blocking filters (see figure) have been developed for microcalorimeters on several mission payloads, made of high-transmission polyimide support mesh, that can replace the nickel mesh used in previous blocking filter flight designs. To realize the resolution and signal sensitivity of today s x-ray microcalorimeters, significant improvements in the blocking filter stack are needed. Using high-transmission polyimide support mesh, it is possible to improve overall throughput on a typical microcalorimeter such as Suzaku s X-ray Spectrometer by 11%, compared to previous flight designs. Using polyimide to replace standard metal mesh means the mesh will be transparent to energies 3 keV and higher. Incorporating polyimide s advantageous strength-to-weight ratio, thermal stability, and transmission characteristics permits thinner filter materials, significantly enhancing through - put. A prototype contamination blocking filter for ASTRO-H has passed QT-level acoustic testing. Resistive traces can also be incorporated to provide decontamination capability to actively restore filter performance in orbit.
Development of a DOI PET Detector Having the Structure of the X'tal Cube Extended in One Direction
NASA Astrophysics Data System (ADS)
Inadama, Naoko; Hirano, Yoshiyuki; Nishikido, Fumihiko; Murayama, Hideo; Yamaya, Taiga
2016-10-01
X'tal cube is the cubic depth of interaction (DOI) PET detector which our research group developed. In this work, aiming to get higher sensitivity, we developed the long rectangular shape X'tal cube (long-XC) by extending the cubic X'tal cube structure in one direction. We verified performance of this long-XC and also studied detector parameters for optimization. The same as the X'tal cube, the crystal block of the long-XC is composed of a 3D array of cubic scintillation crystal elements. Reflectors are not inserted between these crystal elements. The scintillation light then spreads without being obstructed by reflectors and is detected by multiple numbers of the multi-pixel photon counters (MPPCs) coupled on all six sides of the crystal block. For crystal element identification, a simple Anger-type calculation is used. In this study, we arranged 3.0 mm×3.0 mm×3.0 mm LGSO crystal elements in a 6 × 6 × 14 array for the long-XC. In a previous study, we had already confirmed that for the X'tal cube consisting of a 6 × 6 × 6 array of the same crystal elements and 54 MPPCs, identification of all 216 crystal elements was possible and the average energy resolution for all the elements was about 11 %. The long-XC contains more than twice the number of the crystal elements but less than twice the number of the MPPCs compared to the previous X'tal cube. The detector parameters investigated with the long-XC were: the number of MPPCs on both sides in the extended direction (edge MPPCs); the MPPC type, the MPPCs of 25 μm × 25 μm or 50 μm × 50 μm pixel sizes; the material between the crystal elements, an air gap or an optical glue having a closer refractive index to that of LGSO than air has; and the MPPC signals used in the Anger-type calculation. Results of the crystal element identification performance showed that reducing the number of the edge MPPCs caused performance degradation only at the part near the edge. For the MPPC type, the 50 μm type was better than the 25 μm type, and for the material, air was much better than the optical glue. We found that the choice of MPPC signals for the Anger-type calculation was effective in the optical glue condition. For the long-XC in the air gap condition and using the 50 μm type MPPCs, we observed it had good performance and there was no significant degradation at the central part which is far from the edge MPPCs. For irradiation of 662 keV gamma-rays, we measured approximately 11 - 13 % energy resolution for each crystal element and there was only a small difference in light outputs between crystal elements at the central part and at the edges. These results at the central part suggested the possibility of further extension of the long-XC for higher sensitivity.
Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia
Powell, Frank L.; Bisgard, Gerald E.; Blain, Gregory M.; Poulin, Marc J.; Smith, Curtis A.
2013-01-01
During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of “sleep high-train low”! PMID:24371017
Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia.
Dempsey, Jerome A; Powell, Frank L; Bisgard, Gerald E; Blain, Gregory M; Poulin, Marc J; Smith, Curtis A
2014-04-01
During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!
Brief debrisoquin administration to assess central dopaminergic function in children.
Riddle, M A; Shaywitz, B A; Leckman, J F; Anderson, G M; Shaywitz, S E; Hardin, M T; Ort, S I; Cohen, D J
1986-03-17
Central dopaminergic (DA) function in children was assessed by monitoring plasma-free homovanillic acid (pHVA) levels after brief (18 hour) administration with debrisoquin sulfate, a peripherally active antihypertensive agent that blocks peripheral, but not central, HVA production. Brief debrisoquin administration resulted in marked reductions in pHVA in each of six patients studied. In five of the six patients, post-debrisoquin pHVA levels remained relatively stable over the six-hour period of observation. No significant cardiovascular or behavioral side effects of debrisoquin were observed. The brief debrisoquin administration method appears to be a safe, simple, and potentially valid peripheral technique for evaluating aspects of central dopaminergic function in children with neuropsychiatric disorders. Additional work is needed to further establish this method's validity and reliability.
X-ray structures and mechanism of the human serotonin transporter.
Coleman, Jonathan A; Green, Evan M; Gouaux, Eric
2016-04-21
The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.
Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system
Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.
2016-01-01
Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391
NASA Astrophysics Data System (ADS)
Dixon, Timothy H.; Xie, Surui
2018-07-01
The Eastern California shear zone in the Mojave Desert, California, accommodates nearly a quarter of Pacific-North America plate motion. In south-central Mojave, the shear zone consists of six active faults, with the central Calico fault having the fastest slip rate. However, faults to the east of the Calico fault have larger total offsets. We explain this pattern of slip rate and total offset with a model involving a crustal block (the Mojave Block) that migrates eastward relative to a shear zone at depth whose position and orientation is fixed by the Coachella segment of the San Andreas fault (SAF), southwest of the transpressive "big bend" in the SAF. Both the shear zone and the Garlock fault are assumed to be a direct result of this restraining bend, and consequent strain redistribution. The model explains several aspects of local and regional tectonics, may apply to other transpressive continental plate boundary zones, and may improve seismic hazard estimates in these zones.
Multimodal analgesia and regional anaesthesia.
Tornero Tornero, C; Fernández Rodríguez, L E; Orduña Valls, J
Multimodal analgesia provides quality analgesia, with fewer side effects due to the use of combined analgesics or analgesic techniques. Regional anaesthesia plays a fundamental role in achieving this goal. The different techniques of regional anaesthesia that include both peripheral and central blocks in either a single dose or in continuous infusion help to modulate the nociceptive stimuli that access the central level. The emergence of the ultrasound as an effective system to perform regional anaesthesia techniques has allowed the development of new regional anaesthesia techniques that formerly could not be carried out since only neurostimulation or skin references were used. It is essential to take into account that even with effective blocking it is advisable to associate other drugs by other routes, in this way we will be able to reduce the required doses individually and attempt to achieve a synergistic, not purely additive, effect. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.