Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

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Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

2010-06-01

There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

Fast oscillations in cortical-striatal networks switch frequency following rewarding events and stimulant drugs.

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Berke, J D

2009-09-01

Oscillations may organize communication between components of large-scale brain networks. Although gamma-band oscillations have been repeatedly observed in cortical-basal ganglia circuits, their functional roles are not yet clear. Here I show that, in behaving rats, distinct frequencies of ventral striatal local field potential oscillations show coherence with different cortical inputs. The approximately 50 Hz gamma oscillations that normally predominate in awake ventral striatum are coherent with piriform cortex, whereas approximately 80-100 Hz high-gamma oscillations are coherent with frontal cortex. Within striatum, entrainment to gamma rhythms is selective to fast-spiking interneurons, with distinct fast-spiking interneuron populations entrained to different gamma frequencies. Administration of the psychomotor stimulant amphetamine or the dopamine agonist apomorphine causes a prolonged decrease in approximately 50 Hz power and increase in approximately 80-100 Hz power. The same frequency switch is observed for shorter epochs spontaneously in awake, undrugged animals and is consistently provoked for reward receipt. Individual striatal neurons can participate in these brief high-gamma bursts with, or without, substantial changes in firing rate. Switching between discrete oscillatory states may allow different modes of information processing during decision-making and reinforcement-based learning, and may also be an important systems-level process by which stimulant drugs affect cognition and behavior.

DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

Science.gov (United States)

Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

2013-07-01

The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

Glycogen depletion and resynthesis during 14 days of chronic low-frequency stimulation of rabbit muscle

DEFF Research Database (Denmark)

Prats, C; Bernal, C; Cadefau, J A

2002-01-01

Electro-stimulation alters muscle metabolism and the extent of this change depends on application intensity and duration. The effect of 14 days of chronic electro-stimulation on glycogen turnover and on the regulation of glycogen synthase in fast-twitch muscle was studied. The results showed that...

Luminol-dependent chemiluminescence in antibody-sensitized neutrophils stimulated with protein A-bearing staphylococci.

Science.gov (United States)

Nishihara, S; Seki, K; Ikigai, H; Masuda, S

1988-01-01

When mouse polymorphonuclear leukocytes (PMNs) sensitized with rabbit antibody to mouse Ehrlich ascites tumor cells were stimulated by Staphylococcus aureus Cowan I cells, a conspicuous luminol-dependent chemiluminescence was observed in the absence of opsonin. The profile of the chemiluminescence (CL) response evoked by staphylococcal cells from antibody-sensitized PMNs had two peaks. An initial peak, observed within 1 min after stimulation, was sharp and high and a second peak, observed about 5 min after stimulation, was low and extended. The CL response of antibody-sensitized PMNs stimulated by S. aureus Cowan I cells was dose-dependently blocked by preincubation with soluble SpA. Cells of a mutant derived from S. aureus Cowan I strain with trace amounts of cell-bound SpA failed to stimulate the antibody-sensitized PMNs to generate the CL response. The antibody-sensitized PMNs were found to phagocytize SpA-bearing S. aureus cells even in the absence of opsonic serum. These results suggest that the observation presented here might provide a useful tool for the investigation of CL response of PMNs.

FAST: a three-dimensional time-dependent FEL simulation code

International Nuclear Information System (INIS)

Saldin, E.L.; Schneidmiller, E.A.; Yurkov, M.V.

1999-01-01

In this report we briefly describe the three-dimensional, time-dependent FEL simulation code FAST. The equations of motion of the particles and Maxwell's equations are solved simultaneously taking into account the slippage effect. Radiation fields are calculated using an integral solution of Maxwell's equations. A special technique has been developed for fast calculations of the radiation field, drastically reducing the required CPU time. As a result, the developed code allows one to use a personal computer for time-dependent simulations. The code allows one to simulate the radiation from the electron bunch of any transverse and longitudinal bunch shape; to simulate simultaneously an external seed with superimposed noise in the electron beam; to take into account energy spread in the electron beam and the space charge fields; and to simulate a high-gain, high-efficiency FEL amplifier with a tapered undulator. It is important to note that there are no significant memory limitations in the developed code and an electron bunch of any length can be simulated

Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

International Nuclear Information System (INIS)

Oniya, E.O.; Polymeris, G.S.; Tsirliganis, N.C.; Kitis, G.

2012-01-01

The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm −2 ) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C 1 with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C 2 with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C 3 with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: ► The fast OSL component consists of three components. ► The linearity of first fast component does not depend on radiation history. ► The linearity of second and third components depend on radiation history. ► The TL between 180 and 300 °C is the major source of OSL.

Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

Science.gov (United States)

Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

2015-01-01

Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

Modulation of Corticospinal Excitability Depends on the Pattern of Mechanical Tactile Stimulation

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Sho Kojima

2018-01-01

Full Text Available We investigated the effects of different patterns of mechanical tactile stimulation (MS on corticospinal excitability by measuring the motor-evoked potential (MEP. This was a single-blind study that included nineteen healthy subjects. MS was applied for 20 min to the right index finger. MS intervention was defined as simple, lateral, rubbing, vertical, or random. Simple intervention stimulated the entire finger pad at the same time. Lateral intervention stimulated with moving between left and right on the finger pad. Rubbing intervention stimulated with moving the stimulus probe, fixed by protrusion pins. Vertical intervention stimulated with moving in the forward and backward directions on the finger pad. Random intervention stimulated to finger pad with either row protrudes. MEPs were measured in the first dorsal interosseous muscle to transcranial magnetic stimulation of the left motor cortex before, immediately after, and 5–20 min after intervention. Following simple intervention, MEP amplitudes were significantly smaller than preintervention, indicating depression of corticospinal excitability. Following lateral, rubbing, and vertical intervention, MEP amplitudes were significantly larger than preintervention, indicating facilitation of corticospinal excitability. The modulation of corticospinal excitability depends on MS patterns. These results contribute to knowledge regarding the use of MS as a neurorehabilitation tool to neurological disorder.

Modulation of Corticospinal Excitability Depends on the Pattern of Mechanical Tactile Stimulation.

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Kojima, Sho; Onishi, Hideaki; Miyaguchi, Shota; Kotan, Shinichi; Sasaki, Ryoki; Nakagawa, Masaki; Kirimoto, Hikari; Tamaki, Hiroyuki

2018-01-01

We investigated the effects of different patterns of mechanical tactile stimulation (MS) on corticospinal excitability by measuring the motor-evoked potential (MEP). This was a single-blind study that included nineteen healthy subjects. MS was applied for 20 min to the right index finger. MS intervention was defined as simple, lateral, rubbing, vertical, or random. Simple intervention stimulated the entire finger pad at the same time. Lateral intervention stimulated with moving between left and right on the finger pad. Rubbing intervention stimulated with moving the stimulus probe, fixed by protrusion pins. Vertical intervention stimulated with moving in the forward and backward directions on the finger pad. Random intervention stimulated to finger pad with either row protrudes. MEPs were measured in the first dorsal interosseous muscle to transcranial magnetic stimulation of the left motor cortex before, immediately after, and 5-20 min after intervention. Following simple intervention, MEP amplitudes were significantly smaller than preintervention, indicating depression of corticospinal excitability. Following lateral, rubbing, and vertical intervention, MEP amplitudes were significantly larger than preintervention, indicating facilitation of corticospinal excitability. The modulation of corticospinal excitability depends on MS patterns. These results contribute to knowledge regarding the use of MS as a neurorehabilitation tool to neurological disorder.

Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent

International Nuclear Information System (INIS)

Magliola, L.; Jones, A.W.

1987-01-01

The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase 42 K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated 36 Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated 42 K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated 42 K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit 42 K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated 42 K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the 42 K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated 42 K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists

Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

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Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

2013-04-01

Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review.

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Alabbood, Majid H; Ho, Kenneth W; Simons, Mary R

Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin-treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast. Four databases (Medline, EMBASE, Scopus and PubMed) were searched using the following MeSH terms and keywords: "insulin dependent diabetes mellitus", "type 1 diabetes mellitus", 'Ramadan' "and" "fasting". In addition, a hand search of key journals and reference lists was performed. Sixteen full text articles were selected for review and critical analysis. All of the included studies except one found improvement or no change in glycaemic control parameters during Ramadan fasting. The incidence of major complications were negligible. Minor hypoglycaemic events were reported in some studies but did not adversely affect fasting. Postprandial hyperglycaemia was a major concern in other studies. However, the incidence of severe hyperglycaemia and diabetic ketoacidosis were trivial. Ramadan fasting is feasible for insulin dependent diabetic patient who wish to fast. Clinicians should advise their patients about the importance of adequate glycaemic control before Ramadan and frequent glucose monitoring during fasting. Certain types of Insulin seem to be more beneficial than other. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

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Hussain, Sara J; Thirugnanasambandam, Nivethida

2017-06-01

Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders. Copyright © 2017 the American Physiological Society.

GABAB Receptor Stimulation Accentuates the Locomotor Effects of Morphine in Mice Bred for Extreme Sensitivity to the Stimulant Effects of Ethanol

OpenAIRE

Holstein, Sarah E.; Phillips, Tamara J.

2006-01-01

Mice selectively bred for divergent sensitivity to the locomotor stimulant effects of ethanol (FAST and SLOW) also differ in their locomotor response to morphine. The GABAB receptor has been implicated in the mediation of locomotor stimulation to both ethanol and morphine, and a reduction in ethanol-induced stimulation has been found with the GABAB receptor agonist baclofen in FAST mice. We hypothesized that GABAB receptor activation would also attenuate the locomotor stimulant responses to m...

The Polarity-Dependent Effects of the Bilateral Brain Stimulation on Working Memory

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Fatemeh Keshvari

2013-08-01

Full Text Available Introduction: Working memory plays a critical role in cognitive processes which are central to our daily life. Neuroimaging studies have shown that one of the most important areas corresponding to the working memory is the dorsolateral prefrontal cortex (DLFPC. This study was aimed to assess whether bilateral modulation of the DLPFC using a noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS, modi.es the working memory function in healthy adults.Methods: In a randomized sham-controlled cross-over study, 60 subjects (30 Males received sham and active tDCS in two subgroups (anode left/cathode right and anode right/cathode left of the DLPFC. Subjects were presented working memory n-back task while the reaction time and accuracy were recorded.Results: A repeated measures, mixed design ANOVA indicated a signi.cant difference between the type of stimulation (sham vs. active in anodal stimulation of the left DLPFC with cathodal stimulation of the right DLPFC [F(1,55= 5.29,  P=0.019], but not the inverse polarity worsened accuracy in the 2-back working memory task. There were also no statistically signi.cant changes in speed of working memory [F(1,55= 0.458 ,P=0.502] related to type or order of stimulation..Discussion: The results would imply to a polarity dependence of bilateral tDCS of working memory. Left anodal/ right cathodal stimulation of DLPFC could impair working memory, while the reverser stimulation had no effect. Meaning that bilateral stimulation of DLFC would not be a useful procedure to improve working memory. Further studies are required to understand subtle effects of different tDCS stimulation/inhibition electrode positioning on the working memory.

Analysis of cavity effect on space- and time-dependent fast and thermal neutron energy spectra

International Nuclear Information System (INIS)

Kudo, Katsuhisa; Narita, Masakuni; Ozawa, Yasutomo.

1975-01-01

The effects of the presence of a central cavity on the space- and time-dependent neutron energy spectra in both thermal and fast neutron systems are analyzed theoretically with use made of the multi-group one-dimensional time-dependent Ssub(n) method. The thermal neutron field is also analyzed for the case of a fundamental time eigenvalue problem with the time-dependent P 1 approximation. The cavity radius is variable, and the system radius for graphite is 120 cm and for the other materials 7 cm. From the analysis of the time-dependent Ssub(n) calculations in the non-multiplying systems of polythene, light water and graphite, cavity heating is the dominant effect for the slowing-down spectrum in the initial period following fast neutron burst, and when the slowing-down spectrum comes into the thermal energy region, cavity heating shifts to cavity cooling. In the multiplying system of 235 U, cavity cooling also takes place as the spectrum approaches equilibrium after the fast neutron burst is injected. The mechanism of cavity cooling is explained analytically for the case of thermal neutron field to illustrate its physical aspects, using the time-dependent P 1 approximation. An example is given for the case of light water. (auth.)

Task-dependent inhibition of slow-twitch soleus and excitation of fast-twitch gastrocnemius do not require high movement speed and velocity-dependent sensory feedback

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Ricky eMehta

2014-10-01

Full Text Available Although individual heads of triceps surae, soleus (SO and medial gastrocnemius (MG muscles, are often considered close functional synergists, previous studies have shown distinct activity patterns between them in some motor behaviors. The goal of this study was to test two hypotheses explaining inhibition of slow SO with respect to fast MG: (1 inhibition occurs at high movement velocities and mediated by velocity-dependent sensory feedback and (2 inhibition depends on the ankle-knee joint moment combination and does not require high movement velocities. The hypotheses were tested by comparing the SO EMG/MG EMG ratio during fast and slow motor behaviors (cat paw shake responses vs. back, straight leg load lifting in humans, which had the same ankle extension-knee flexion moment combination; and during fast and slow behaviors with the ankle extension-knee extension moment combination (human vertical jumping and stance phase of walking in cats and leg load lifting in humans. In addition, SO EMG/MG EMG ratio was determined during cat paw shake responses and walking before and after removal of stretch velocity-dependent sensory feedback by self-reinnervating SO and/or gastrocnemius. We found the ratio SO EMG/MG EMG below 1 (p<0.05 during fast paw shake responses and slow back load lifting, requiring the ankle extension-knee flexion moment combination; whereas the ratio SO EMG/MG EMG was above 1 (p<0.05 during fast vertical jumping and slow tasks of walking and leg load lifting, requiring ankle extension-knee extension moments. Removal of velocity-dependent sensory feedback did not affect the SO EMG/MG EMG ratio in cats. We concluded that the relative inhibition of SO does not require high muscle velocities, depends on ankle-knee moment combinations, and is mechanically advantageous for allowing a greater MG contribution to ankle extension and knee flexion moments.

Fast and Cache-Oblivious Dynamic Programming with Local Dependencies

DEFF Research Database (Denmark)

Bille, Philip; Stöckel, Morten

2012-01-01

are widely used in bioinformatics to compare DNA and protein sequences. These problems can all be solved using essentially the same dynamic programming scheme over a two-dimensional matrix, where each entry depends locally on at most 3 neighboring entries. We present a simple, fast, and cache......-oblivious algorithm for this type of local dynamic programming suitable for comparing large-scale strings. Our algorithm outperforms the previous state-of-the-art solutions. Surprisingly, our new simple algorithm is competitive with a complicated, optimized, and tuned implementation of the best cache-aware algorithm...

Nobiletin Stimulates Chloride Secretion in Human Bronchial Epithelia via a cAMP/PKA-Dependent Pathway

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Yuan Hao

2015-08-01

Full Text Available Background/Aims: Nobiletin, a citrus flavonoid isolated from tangerines, alters ion transport functions in intestinal epithelia, and has antagonistic effects on eosinophilic airway inflammation of asthmatic rats. The present study examined the effects of nobiletin on basal short-circuit current (ISC in a human bronchial epithelial cell line (16HBE14o-, and characterized the signal transduction pathways that allowed nobiletin to regulate electrolyte transport. Methods: The ISC measurement technique was used for transepithelial electrical measurements. Intracellular calcium ([Ca2+]i and cAMP were also quantified. Results: Nobiletin stimulated a concentration-dependent increase in ISC, which was due to Cl- secretion. The increase in ISC was inhibited by a cystic fibrosis transmembrane conductance regulator inhibitor (CFTRinh-172, but not by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS, Chromanol 293B, clotrimazole, or TRAM-34. Nobiletin-stimulated ISC was also sensitive to a protein kinase A (PKA inhibitor, H89, and an adenylate cyclase inhibitor, MDL-12330A. Nobiletin could not stimulate any increase in ISC in a cystic fibrosis (CF cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a real-time increase in cAMP, but not [Ca2+]i. Conclusion: Nobiletin stimulated transepithelial Cl- secretion across human bronchial epithelia. The mechanisms involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways, leading to activation of apical CFTR Cl- channels.

Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

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Meunier, David; Ersche, Karen D; Craig, Kevin J; Fornito, Alex; Merlo-Pich, Emilio; Fineberg, Naomi A; Shabbir, Shaila S; Robbins, Trevor W; Bullmore, Edward T

2012-01-16

There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories. Copyright © 2011 Elsevier Inc. All rights reserved.

The Effect of Lamotrigine and Levetiracetam on TMS-Evoked EEG Responses Depends on Stimulation Intensity

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Isabella Premoli

2017-10-01

Full Text Available The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG has uncovered underlying mechanisms of two anti-epileptic medications: levetiracetam and lamotrigine. Despite their different mechanism of action, both drugs modulated TMS-evoked EEG potentials (TEPs in a similar way. Since both medications increase resting motor threshold (RMT, the current aim was to examine the similarities and differences in post-drug TEPs, depending on whether stimulation intensity was adjusted to take account of post-drug RMT increase. The experiment followed a placebo controlled, double blind, crossover design, involving a single dose of either lamotrigine or levetiracetam. When a drug-induced increase of RMT occurred, post-drug measurements involved two blocks of stimulations, using unadjusted and adjusted stimulation intensity. A cluster based permutation analysis of differences in TEP amplitude between adjusted and unadjusted stimulation intensity showed that lamotrigine induced a stronger modulation of the N45 TEP component compared to levetiracetam. Results highlight the impact of adjusting stimulation intensity.

Fasting plasma triglycerides predict the glycaemic response to treatment of Type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm

Science.gov (United States)

Lebovitz, H E; Ludvik, B; Yaniv, I; Haddad, W; Schwartz, T; Aviv, R

2013-01-01

Background Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level. Method An analysis of 40 patients who had had detailed longitudinal studies for 12 months. Results Twenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of −15 ± 2.1 mmol/mol (−1.39 ± 0.20%), −16 ± 2.2 mmol/mol (−1.48 ± 0.20%) and −14 ± 3.0 mmol/mol (−1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of −7 ± 1.7 mmol/mol (−0.66 ± 0.16%), −5 ± 1.6 mmol/mol (−0.44 ± 0.18%) and −5 ± 1.7 mmol/mol (−0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P triglycerides, while it progressively improved in patients with low fasting plasma triglycerides. Patients with low fasting plasma triglycerides had a tendency to lose more weight than those with high fasting plasma triglycerides, but this did not achieve statistical significance. Conclusions The data presented suggest the existance of a triglyceride lipotoxic mechanism that interferes with gastric/neural mediated pathways that can regulate glycaemic control in patients with type 2 diabetes. The data suggest the existence of a triglyceride lipotoxic pathway that interferes with gastric/neural mediated pathways that can regulate glycaemic control

Fast periodic stimulation (FPS): a highly effective approach in fMRI brain mapping.

Science.gov (United States)

Gao, Xiaoqing; Gentile, Francesco; Rossion, Bruno

2018-03-03

Defining the neural basis of perceptual categorization in a rapidly changing natural environment with low-temporal resolution methods such as functional magnetic resonance imaging (fMRI) is challenging. Here, we present a novel fast periodic stimulation (FPS)-fMRI approach to define face-selective brain regions with natural images. Human observers are presented with a dynamic stream of widely variable natural object images alternating at a fast rate (6 images/s). Every 9 s, a short burst of variable face images contrasting with object images in pairs induces an objective face-selective neural response at 0.111 Hz. A model-free Fourier analysis achieves a twofold increase in signal-to-noise ratio compared to a conventional block-design approach with identical stimuli and scanning duration, allowing to derive a comprehensive map of face-selective areas in the ventral occipito-temporal cortex, including the anterior temporal lobe (ATL), in all individual brains. Critically, periodicity of the desired category contrast and random variability among widely diverse images effectively eliminates the contribution of low-level visual cues, and lead to the highest values (80-90%) of test-retest reliability in the spatial activation map yet reported in imaging higher level visual functions. FPS-fMRI opens a new avenue for understanding brain function with low-temporal resolution methods.

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

Directory of Open Access Journals (Sweden)

Marques-da-Silva A.C.

1997-01-01

Full Text Available The influence of Ca2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD+-NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD+-NADH potentials were changed by varying the lactate to pyruvate ratios from 0.01 to 100. The following results were obtained: a gluconeogenesis from lactate plus pyruvate was not affected by Ca2+-free perfusion (no Ca2+ in the perfusion fluid combined with previous depletion of the intracellular pools; gluconeogenesis was also poorly dependent on the lactate to pyruvate ratios in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other ratios. b In the presence of Ca2+, the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca2+-free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for a lactate/pyruvate ratio equal to 1. c In the presence of Ca2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate ratios; for a ratio equal to 0.01 no stimulation occurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d In the absence of Ca2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

Science.gov (United States)

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes

DEFF Research Database (Denmark)

Gjessing, H J; Matzen, L E; Faber, O K

1989-01-01

with a fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C...

Fast-ball sports experts depend on an inhibitory strategy to reprogram their movement timing.

Science.gov (United States)

Nakamoto, Hiroki; Ikudome, Sachi; Yotani, Kengo; Maruyama, Atsuo; Mori, Shiro

2013-07-01

The purpose of our study was to clarify whether an inhibitory strategy is used for reprogramming of movement timing by experts in fast-ball sports when they correct their movement timing due to unexpected environmental changes. We evaluated the influence of disruption of inhibitory function of the right inferior frontal gyrus (rIFG) on reprogramming of movement timing of experts and non-experts in fast-ball sports. The task was to manually press a button to coincide with the arrival of a moving target. The target moved at a constant velocity, and its velocity was suddenly either increased or decreased in some trials. The task was performed either with or without transcranial magnetic stimulation (TMS), which was delivered to the region of the rIFG. Under velocity change conditions without TMS, the experts showed significantly smaller timing errors and a higher rate of reprogramming of movement timing than the non-experts. Moreover, TMS application during the task significantly diminished the expert group's performance, but not the control group, particularly in the condition where the target velocity decreases. These results suggest that experts use an inhibitory strategy for reprogramming of movement timing. In addition, the rIFG inhibitory function contributes to the superior movement correction of experts in fast-ball sports.

Fast neutrons-induced apoptosis is Fas-independent in lymphoblastoid cells

International Nuclear Information System (INIS)

Fischer, Barbara; Benzina, Sami; Jeannequin, Pierre; Dufour, Patrick; Bergerat, Jean-Pierre; Denis, Jean-Marc; Gueulette, John; Bischoff, Pierre L.

2005-01-01

We have previously shown that ionizing radiation-induced apoptosis in human lymphoblastoid cells differs according to their p53 status, and that caspase 8-mediated cleavage of BID is involved in the p53-dependent pathway. In the present study, we investigated the role of Fas signaling in caspase 8 activation induced by fast neutrons irradiation in these cells. Fas and FasL expression was assessed by flow cytometry and by immunoblot. We also measured Fas aggregation after irradiation by fluorescence microscopy. We found a decrease of Fas expression after irradiation, but no change in Fas ligand expression. We also showed that, in contrast to the stimulation of Fas by an agonistic antibody, Fas aggregation did not occur after irradiation. Altogether, our data strongly suggest that fast neutrons induced-apoptosis is Fas-independent, even in p53-dependent apoptosis

Sex differences in disinhibition and its relationship to physical abuse in a sample of stimulant-dependent patients.

Science.gov (United States)

Winhusen, Theresa; Lewis, Daniel

2013-04-01

Research suggests that impulsivity is a vulnerability factor for developing stimulant dependence, that women develop dependence more quickly than men, and that physical abuse can increase impulsivity and may have greater adverse health consequences in women. This study sought to tie these findings together by evaluating: (1) sex differences in disinhibition prior to lifetime initiation of stimulant abuse and (2) the relationship between physical abuse and disinhibition in stimulant-dependent patients. The Frontal Systems Behavior Scale (FrSBe) is a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses pre-morbid functioning and has a specific cutoff for defining clinically significant abnormalities. Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 118 methamphetamine- and/or cocaine-dependent participants. Lifetime physical abuse was measured by the Addiction Severity Index (ASI). The proportion reporting clinically significant disinhibition was significantly higher in women (64.9%) than in men (45.0%, p=0.04), with no significant difference on the other FrSBe scales. Physical abuse in women, but not men, was associated with worse functioning, with physically abused, relative to non-abused, women having a significantly greater proportion with clinically significant disinhibition (pabuse and that physical abuse in women is associated with greater disinhibition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2.

Science.gov (United States)

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

2015-06-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population.

Science.gov (United States)

Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

2015-06-01

Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. The current study was a correlation study. We evaluated 285 male substance users and excluded 25 according to exclusion criteria. A total of 130 narcotic users and 130 stimulant users were recruited randomly in several phases from January 2013 to October 2013. All participants were referred to Substance Dependency Treatment Clinics in Tehran, Iran. Data collection process was accomplished by means of clinical interview based on DSM-V criteria for substance use disorders, Iranian version of addiction severity index (ASI), and Millon clinical multi-axial inventory-III (MCMI-III). Data were analyzed by SPSS 21 using Pearson correlation coefficient and regression, the. There was a significant correlation between stimulant use and histrionic personality disorder (P personality disorders (P histrionic, and narcissistic personality disorders (P personality disorders (P personality disorders, and narcotic and stimulants consumption (P personality disorder and narcotics (P personality disorders and types of used drugs were in accordance with the previous studies results. It is necessary to design appropriate treatment plans for medical treatment of those with personality disorders.

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

DEFF Research Database (Denmark)

Pham, Minh-Long; Kolb, H; Battelino, T

2013-01-01

Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes.......Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes....

Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

Science.gov (United States)

Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

2015-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson's disease (PD). However, some aspects of executive control are impaired with STN DBS. We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

Dependence of (anomalous) fading of infra-red stimulated luminescence on trap occupancy in feldspars

DEFF Research Database (Denmark)

Morthekai, P.; Jain, Mayank; Gach, Grzegorz

2013-01-01

Dose dependency of anomalous fading of infra-red stimulated luminescence (IRSL) from feldspars has been investigated using radiations of different ionisation qualities. The rate of fading of the IRSL signal after proton irradiation (9.4–30%/decade) is on an average almost twice compared...

Increased CEST specificity for amide and fast-exchanging amine protons using exchange-dependent relaxation rate.

Science.gov (United States)

Zhang, Xiao-Yong; Wang, Feng; Xu, Junzhong; Gochberg, Daniel F; Gore, John C; Zu, Zhongliang

2018-02-01

Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and fast-exchanging amines at 3 ppm provides a unique means to enhance the sensitivity of detection of, for example, proteins/peptides and neurotransmitters, respectively, and hence can provide important information on molecular composition. However, despite the high sensitivity relative to conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has relatively poor specificity. For example, CEST signals are typically influenced by several confounding effects, including direct water saturation (DS), semi-solid non-specific magnetization transfer (MT), the influence of water relaxation times (T 1w ) and nearby overlapping CEST signals. Although several editing techniques have been developed to increase the specificity by removing DS, semi-solid MT and T 1w influences, it is still challenging to remove overlapping CEST signals from different exchanging sites. For instance, the amide proton transfer (APT) signal could be contaminated by CEST effects from fast-exchanging amines at 3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an exchange-dependent relaxation rate (R ex ) to address this problem. Simulations demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have distinct dependences on irradiation powers; and (2) R ex serves as a resonance frequency high-pass filter to selectively reduce CEST signals with resonance frequencies closer to water. These characteristics of R ex provide a means to isolate the APT signal from amines. In addition, previous studies have shown that CEST signals from fast-exchanging amines have no distinct features around their resonance frequencies. However, R ex gives Lorentzian lineshapes centered at their resonance frequencies for fast-exchanging amines and thus can significantly increase the specificity of CEST imaging for amides and fast-exchanging amines. Copyright © 2017 John Wiley & Sons

Time dependent solutions of the Fokker-Planck equation for fast fusion ions

International Nuclear Information System (INIS)

Gnavi, G.; Gratton, F.T.; Heyn, M.

1990-01-01

Approximate time dependent solutions for the Fokker-Planck equation for fast fusion ions from an isotropic, monoenergetic source are presented, for the problem of D - T - He 3 reactions. The equations include the effect of diffusion, which is particularly noticeable in the distribution of particles of lower energy and in the formation of a tail of particles with energy higher than that of the source. (Author)

Seeding of Polariton Stimulation in a Homogeneously Broadened Microcavity

DEFF Research Database (Denmark)

Østergaard, John Erland; Langbein, Wolfgang Werner; Jensen, Jacob Riis

2000-01-01

In time-resolved light emission from a high-quality semiconductor microcavity after pulsed excitation suitable for angle-resonant polariton-polariton scattering on the lower-polariton branch, we find strong evidence for final-state stimulation of this process. The self-stimulated emission...... and the intensity of this emission can be controlled. The time-resolved data and the density dependences are in agreement with a rate equation model neglecting polarization mixing effects. This model gives a coupling coefficient of b(LP,k)=0 = 2.4 x 10(-9) cm(4) s(-1) for the stimulated angle-resonant polariton......, following single-pulse excitation, appears on a fast time scale of only a few lens of ps with a maximum at 15 ps. This is in striking contrast to the photoluminescence decay time of 110 ps observed in the low-density limit. By injection of polaritons into the final state by a seeding pulse, the dynamics...

GH signaling in human adipose and muscle tissue during 'feast and famine': amplification of exercise stimulation following fasting compared to glucose administration.

Science.gov (United States)

Vendelbo, Mikkel H; Christensen, Britt; Grønbæk, Solbritt B; Høgild, Morten; Madsen, Michael; Pedersen, Steen B; Jørgensen, Jens O L; Jessen, Niels; Møller, Niels

2015-09-01

Fasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original 'feast and famine hypothesis' by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression. Eight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion ('feast') and ii) after a 36 h fast ('famine'). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise. GH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days. This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the 'feast and famine hypothesis'; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization. © 2015 European Society of Endocrinology.

Dependence of heavy metal burnup on nuclear data libraries for fast reactors

CERN Document Server

Ohki, S

2003-01-01

Japan Nuclear Cycle Development Institute (JNC) is considering the highly burnt fuel as well as the recycling of minor actinide (MA) in the development of commercialized fast reactor cycle systems. Higher accuracy in burnup calculation is going to be required for higher mass plutonium isotopes ( sup 2 sup 4 sup 0 Pu, etc.) and MA nuclides. In the framework of research and development aiming at the validation and necessary improvements of fast reactor burnup calculation, we investigated the differences among the burnup calculation results with the major nuclear data libraries: JEF-2.2, ENDF/B-VI Release 5, JENDL-3.2, and JENDL-3.3. We focused on the heavy metal nuclides such as plutonium and MA in the central core region of a conventional sodium-cooled fast reactor. For main heavy metal nuclides ( sup 2 sup 3 sup 5 U, sup 2 sup 3 sup 8 U, sup 2 sup 3 sup 9 Pu, sup 2 sup 4 sup 0 Pu, and sup 2 sup 4 sup 1 Pu), number densities after 1-cycle burnup did not change over one or two percent. Library dependence was re...

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

OpenAIRE

Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2011-01-01

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess...

Fasts, feasts and festivals in diabetes-1: Glycemic management during Hindu fasts

Directory of Open Access Journals (Sweden)

Sanjay Kalra

2015-01-01

Full Text Available This communication is the first of a series on South Asian fasts, festivals, and diabetes, designed to spread awareness and stimulate research on this aspect of diabetes and metabolic care. It describes the various fasts observed as part of Hindu religion and offers a classification scheme for them, labeling them as infrequent and frequent. The infrequent fasts are further sub-classified as brief and prolonged, to facilitate a scientific approach to glycemic management during these fasts. Pre-fast counseling, non-pharmacological therapy, pharmacological modification, and post-fast debriefing are discussed in detail. All available drug classes and molecules are covered in this article, which provides guidance about necessary changes in dosage and timing of administration. While in no way exhaustive, the brief review offers a basic framework which diabetes care professionals can use to counsel and manage persons in their care who wish to observe various Hindu fasts.

Fast multigrid-based computation of the induced electric field for transcranial magnetic stimulation

Science.gov (United States)

Laakso, Ilkka; Hirata, Akimasa

2012-12-01

In transcranial magnetic stimulation (TMS), the distribution of the induced electric field, and the affected brain areas, depends on the position of the stimulation coil and the individual geometry of the head and brain. The distribution of the induced electric field in realistic anatomies can be modelled using computational methods. However, existing computational methods for accurately determining the induced electric field in realistic anatomical models have suffered from long computation times, typically in the range of tens of minutes or longer. This paper presents a matrix-free implementation of the finite-element method with a geometric multigrid method that can potentially reduce the computation time to several seconds or less even when using an ordinary computer. The performance of the method is studied by computing the induced electric field in two anatomically realistic models. An idealized two-loop coil is used as the stimulating coil. Multiple computational grid resolutions ranging from 2 to 0.25 mm are used. The results show that, for macroscopic modelling of the electric field in an anatomically realistic model, computational grid resolutions of 1 mm or 2 mm appear to provide good numerical accuracy compared to higher resolutions. The multigrid iteration typically converges in less than ten iterations independent of the grid resolution. Even without parallelization, each iteration takes about 1.0 s or 0.1 s for the 1 and 2 mm resolutions, respectively. This suggests that calculating the electric field with sufficient accuracy in real time is feasible.

ITER Plasma at Ion Cyclotron Frequency Domain: The Fusion Alpha Particles Diagnostics Based on the Stimulated Raman Scattering of Fast Magnetosonic Wave off High Harmonic Ion Bernstein Modes

Science.gov (United States)

Stefan, V. Alexander

2014-10-01

A novel method for alpha particle diagnostics is proposed. The theory of stimulated Raman scattering, SRS, of the fast wave and ion Bernstein mode, IBM, turbulence in multi-ion species plasmas, (Stefan University Press, La Jolla, CA, 2008). is utilized for the diagnostics of fast ions, (4)He (+2), in ITER plasmas. Nonlinear Landau damping of the IBM on fast ions near the plasma edge leads to the space-time changes in the turbulence level, (inverse alpha particle channeling). The space-time monitoring of the IBM turbulence via the SRS techniques may prove efficient for the real time study of the fast ion velocity distribution function, spatial distribution, and transport. Supported by Nikola Tesla Labs., La Jolla, CA 92037.

Inhibiting effects of fructanase on competence-stimulating peptide-dependent quorum sensing system in Streptococcus mutans.

Science.gov (United States)

Suzuki, Yusuke; Nagasawa, Ryo; Senpuku, Hidenobu

2017-09-01

Streptococcus mutans produces glucosyltransferases encoded by the gtfB and gtfC genes, which synthesize insoluble glucan, and both insoluble and soluble glucans by conversion of sucrose, and are known as principal agents to provide strong biofilm formation and demineralization on tooth surfaces. S. mutans possess a Com-dependent quorum sensing (QS) system, which is important for survival in severe conditions. The QS system is stimulated by the interaction between ComD {Receptor to competence-stimulating peptide (CSP)} encoded by the comD and CSP encoded by the comC, and importantly associated with bacteriocin production and genetic competence. Previously, we found enzyme fructanase (FruA) as a new inhibitor for the glucan-dependent biofilm formation. In the present study, inhibiting effects by FruA on glucan-independent biofilm formation of S. mutans UA159, UA159.gtfB - , UA159.gtfC - , and UA159.gtfBC - were observed in sucrose and no sucrose sugars-supplemented conditions using the plate assay. The reduction of UA159.comC - and UA159.comD - biofilm formation were also observed as compared with UA159 in same conditions. These results suggested that inhibitions of glucan-independent and Com-dependent biofilm formation were involved in the inhibiting mechanism by FruA. To more thoroughly investigate effects by FruA on the QS system, we examined on CSP-stimulated and Com-dependent bacteriocin production and genetic transformation. FruA inhibited bacteriocin production in collaboration with CSP and genetic transformation in bacterial cell conditions treated with FruA. Our findings show that FruA has multiple effects that inhibit survival functions of S. mutans, including biofilm formation and CSP-dependent QS responses, indicating its potential use as an agent for prevention of dental caries. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

Directory of Open Access Journals (Sweden)

Martina Reske

Full Text Available Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate, which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.158 occasional stimulants users (OSU and 50 comparison subjects (CS performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions". The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42, or <50 lifetime marijuana uses (n = 32, were compared to CS with <50 lifetime uses (n = 46 to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring

SU-E-T-75: Commissioning Optically Stimulated Luminescence Dosimeters for Fast Neutron Therapy

Energy Technology Data Exchange (ETDEWEB)

Young, L [UniversityWashington, Seattle, WA (United States); Yang, F; Sandison, G [University of Washington, Seattle, WA (United States); Woodworth, D [University of California, Santa Barbara, Santa Barbara, CA (United States); McCormick, Z [University of Nevada - Reno, Reno, Nevada (United States)

2014-06-01

Purpose: Fast neutrons therapy used at the University of Washington is clinically proven to be more effective than photon therapy in treating salivary gland and other cancers. A nanodot optically stimulated luminescence (OSL) system was chosen to be commissioned for patient in vivo dosimetry for neutron therapy. The OSL-based radiation detectors are not susceptible to radiation damage caused by neutrons compared to diodes or MOSFET systems. Methods: An In-Light microStar OSL system was commissioned for in vivo use by radiating Landauer nanodots with neutrons generated from 50.0 MeV protons accelerated onto a beryllium target. The OSLs were calibrated the depth of maximum dose in solid water localized to 150 cm SAD isocenter in a 10.3 cm square field. Linearity was tested over a typical clinical dose fractionation range i.e. 0 to 150 neutron-cGy. Correction factors for transient signal fading, trap depletion, gantry angle, field size, and wedge factor dependencies were also evaluated. The OSLs were photo-bleached between radiations using a tungsten-halogen lamp. Results: Landauer sensitivity factors published for each nanodot are valid for measuring photon and electron doses but do not apply for neutron irradiation. Individually calculated nanodot calibration factors exhibited a 2–5% improvement over calibration factors computed by the microStar InLight software. Transient fading effects had a significant impact on neutron dose reading accuracy compared to photon and electron in vivo dosimetry. Greater accuracy can be achieved by calibrating and reading each dosimeter within 1–2 hours after irradiation. No additional OSL correction factors were needed for field size, gantry angle, or wedge factors in solid water phantom measurements. Conclusion: OSL detectors are a useful for neutron beam in vivo dosimetry verification. Dosimetric accuracy comparable to conventional diode systems can be achieved. Accounting for transient fading effects during the neutron beam

Comparison of Experienced Violence in Women with Opiate-Dependent and Stimulant-Dependent Husbands

Directory of Open Access Journals (Sweden)

Neda Ahmadpour

2013-01-01

Full Text Available Objective: Opium and stimulants are two kinds of illegal substances which are different from each other in chemical structure, psychological and biological effects (material, and their potential adverse effects on consumers. The present study compares the effect of abuse of each of the two (opium and stimulants on violent behavior against wives. Materials & Methods: The present study was a non-experimental and comparative study. The study sample included 100 spouses of men addicted to opium and stimulants (50 opium and 50 stimulant addicts who attended governmental or non-governmental centers or camps in Tehran city (from October 2011 to January 2012, in order to receive professional assistances. (Both groups of subjects were selected by convenient sampling method to ensure the compatibility with input and output data. The “revised conflict tactics scale” was used to assess the rates of violence (psychological, sexual coercion, negotiation, injury and physical assault exerted by men. Results were analyzed using multi-variety analysis of variance and covariance. Results: Results showed that after controlling the age as a covariate, consumers of stimulants (especially methamphetamine were more violent toward their wives than were consumers of opium (P&le0.001. There were also significant differences between the two groups in the psychological, sexual coercion, injury and physical assault subscales, but not in the negotiation subscale (P&le0.05. Conclusion: It seems that the psychopharmacological effect of stimulants leads to more violent behaviors in its consumers (especially by methamphetamine than in consumers of opium.

Swelling of rat hepatocytes stimulates glycogen synthesis

NARCIS (Netherlands)

Baquet, A.; Hue, L.; Meijer, A. J.; van Woerkom, G. M.; Plomp, P. J.

1990-01-01

In hepatocytes from fasted rats, several amino acids are known to stimulate glycogen synthesis via activation of glycogen synthase. The hypothesis that an increase in cell volume resulting from amino acid uptake may be involved in the stimulation of glycogen synthesis is supported by the following

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

Science.gov (United States)

Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

Science.gov (United States)

Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

2017-09-01

Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

Directory of Open Access Journals (Sweden)

Wai-Ping Fung-Leung

Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

Muscle fiber type specific induction of slow myosin heavy chain 2 gene expression by electrical stimulation

International Nuclear Information System (INIS)

Crew, Jennifer R.; Falzari, Kanakeshwari; DiMario, Joseph X.

2010-01-01

Vertebrate skeletal muscle fiber types are defined by a broad array of differentially expressed contractile and metabolic protein genes. The mechanisms that establish and maintain these different fiber types vary throughout development and with changing functional demand. Chicken skeletal muscle fibers can be generally categorized as fast and fast/slow based on expression of the slow myosin heavy chain 2 (MyHC2) gene in fast/slow muscle fibers. To investigate the cellular and molecular mechanisms that control fiber type formation in secondary or fetal muscle fibers, myoblasts from the fast pectoralis major (PM) and fast/slow medial adductor (MA) muscles were isolated, allowed to differentiate in vitro, and electrically stimulated. MA muscle fibers were induced to express the slow MyHC2 gene by electrical stimulation, whereas PM muscle fibers did not express the slow MyHC2 gene under identical stimulation conditions. However, PM muscle fibers did express the slow MyHC2 gene when electrical stimulation was combined with inhibition of inositol triphosphate receptor (IP3R) activity. Electrical stimulation was sufficient to increase nuclear localization of expressed nuclear-factor-of-activated-T-cells (NFAT), NFAT-mediated transcription, and slow MyHC2 promoter activity in MA muscle fibers. In contrast, both electrical stimulation and inhibitors of IP3R activity were required for these effects in PM muscle fibers. Electrical stimulation also increased levels of peroxisome-proliferator-activated receptor-γ co-activator-1 (PGC-1α) protein in PM and MA muscle fibers. These results indicate that MA muscle fibers can be induced by electrical stimulation to express the slow MyHC2 gene and that fast PM muscle fibers are refractory to stimulation-induced slow MyHC2 gene expression due to fast PM muscle fiber specific cellular mechanisms involving IP3R activity.

Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging.

Science.gov (United States)

Vidal-Piñeiro, Dídac; Martin-Trias, Pablo; Arenaza-Urquijo, Eider M; Sala-Llonch, Roser; Clemente, Imma C; Mena-Sánchez, Isaias; Bargalló, Núria; Falcón, Carles; Pascual-Leone, Álvaro; Bartrés-Faz, David

2014-01-01

Transcranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. We applied a paradigm of repetitive TMS - intermittent theta-burst stimulation - over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

DEFF Research Database (Denmark)

Friis, P; Svehag, S E; Andersen, Ove

1991-01-01

. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited...

Combining shallow and deep processing for a robust, fast, deep-linguistic dependency parser

OpenAIRE

Schneider, G

2004-01-01

This paper describes Pro3Gres, a fast, robust, broad-coverage parser that delivers deep-linguistic grammatical relation structures as output, which are closer to predicate-argument structures and more informative than pure constituency structures. The parser stays as shallow as is possible for each task, combining shallow and deep-linguistic methods by integrating chunking and by expressing the majority of long-distance dependencies in a context-free way. It combines statistical and rule-base...

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

Directory of Open Access Journals (Sweden)

Clinton B McCracken

Full Text Available High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS, is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP, the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson's disease (PD. We performed simultaneous multi-site local field potential (LFP recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective, low-frequency (LF, 15 Hz; ineffective and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR, ventroanterior thalamus (VA, primary motor cortex (M1, and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic

Experience with "Fast track" postoperative care after deep brain stimulation surgery.

Science.gov (United States)

Martín, Nuria; Valero, Ricard; Hurtado, Paola; Gracia, Isabel; Fernández, Carla; Rumià, Jordi; Valldeoriola, Francesc; Carrero, Enrique J; Tercero, Francisco Javier; de Riva, Nicolás; Fàbregas, Neus

A 24-h-stay in the post-anesthesia care unit (PACU) is a common postoperative procedure after deep brain stimulation surgery (DBS). We evaluated the impact of a fast-track (FT) postoperative care protocol. An analysis was performed on all patients who underwent DBS in 2 periods: 2006, overnight monitored care (OMC group), and 2007-2013, FT care (FT group). The study included 19 patients in OMC and 95 patients in FT. Intraoperative complications occurred in 26.3% patients in OMC vs. 35.8% in FT. Post-operatively, one patient in OMC developed hemiparesis, and agitation in 2 patients. In FT, two patients with intraoperative hemiparesis were transferred to the ICU. While on the ward, 3 patients from the FT developed hemiparesis, two of them 48h after the procedure. Thirty eight percent of FT had an MRI scan, while the remaining 62% and all patients of OMC had a CT-scan performed on their transfer to the ward. One patient in OMC had a subthalamic hematoma. Two patients in FT had a pallidal hematoma, and 3 a bleeding along the electrode. A FT discharge protocol is a safe postoperative care after DBS. There are a small percentage of complications after DBS, which mainly occur within the first 6h. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Glu¹⁰⁶ in the Orai1 pore contributes to fast Ca²⁺-dependent inactivation and pH dependence of Ca²⁺ release-activated Ca²⁺ (CRAC) current.

Science.gov (United States)

Scrimgeour, Nathan R; Wilson, David P; Rychkov, Grigori Y

2012-01-15

FCDI (fast Ca²⁺-dependent inactivation) is a mechanism that limits Ca²⁺ entry through Ca²⁺ channels, including CRAC (Ca²⁺ release-activated Ca²⁺) channels. This phenomenon occurs when the Ca²⁺ concentration rises beyond a certain level in the vicinity of the intracellular mouth of the channel pore. In CRAC channels, several regions of the pore-forming protein Orai1, and STIM1 (stromal interaction molecule 1), the sarcoplasmic/endoplasmic reticulum Ca²⁺ sensor that communicates the Ca²⁺ load of the intracellular stores to Orai1, have been shown to regulate fast Ca²⁺-dependent inactivation. Although significant advances in unravelling the mechanisms of CRAC channel gating have occurred, the mechanisms regulating fast Ca²⁺-dependent inactivation in this channel are not well understood. We have identified that a pore mutation, E106D Orai1, changes the kinetics and voltage dependence of the ICRAC (CRAC current), and the selectivity of the Ca²⁺-binding site that regulates fast Ca²⁺-dependent inactivation, whereas the V102I and E190Q mutants when expressed at appropriate ratios with STIM1 have fast Ca²⁺-dependent inactivation similar to that of WT (wild-type) Orai1. Unexpectedly, the E106D mutation also changes the pH dependence of ICRAC. Unlike WT ICRAC, E106D-mediated current is not inhibited at low pH, but instead the block of Na⁺ permeation through the E106D Orai1 pore by Ca²⁺ is diminished. These results suggest that Glu¹⁰⁶ inside the CRAC channel pore is involved in co-ordinating the Ca²⁺-binding site that mediates fast Ca²⁺-dependent inactivation.

Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.

Science.gov (United States)

Huang, Jinghui; Ye, Zhengxu; Hu, Xueyu; Lu, Lei; Luo, Zhuojing

2010-04-01

Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering.

Charge states of fast heavy ions in solids; target atomic number dependence

International Nuclear Information System (INIS)

Shima, Kunihiro

1985-01-01

Discussions were carried out on the origin of Z 2 (atomic number) dependent charge states with respect to projectile electron loss and capture process, and on relationship between the Z 2 dependence and that of mean charge states for heavy ions of 1 MeV/u energy region. Present and previously reported results were examined on the equilibrium charge distributions, 9-bar, of 120 MeV 63 Cu, 25 and 40 MeV 35 Cl, 109 MeV Si and 59 MeV F ions. It was clarified that 9-bar became generally higher for lower Z 2 depending on increasing energy, and osillatory behavior with energy-depending amplitude was seen in 9-bar vs Z 2 . Discussions were carrid out on these phenomena and related matters. Z 2 oscillations of 9-bar of fast heavy ions might be due to those of electron capture cross section into projectile K and L vacancies for high and intermediate charge states, respectively. A quantitative interpretation of the Z 2 -dependent 9-bar values is in progress based on collision process and observation of projectile x-ray. The 9-bar value dependency on Z 2 in ion passing foils and decrease of Z 2 oscillation amplitude with increasing collision energy were quite similar to the Z 2 dependence in stopping powers or in effective charge states estimated from stopping powers. But there was some discrepancies in the Z 2 oscillation of 9-bar and that of stopping powers. (Takagi, S.)

Gene expression results in lipopolysaccharide-stimulated monocytes depend significantly on the choice of reference genes

Directory of Open Access Journals (Sweden)

Øvstebø Reidun

2010-05-01

Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.

Context-dependent effects of substantia nigra stimulation on eye movements.

Science.gov (United States)

Basso, Michele A; Liu, Ping

2007-06-01

In a series of now classic experiments, an output structure of the basal ganglia (BG)--the substantia nigra pars reticulata (SNr)--was shown to be involved in the generation of saccades made in particular behavioral contexts, such as when memory was required for guidance. Recent electrophysiological experiments, however, call this original hypothesis into question. Here we test the hypothesis that the SNr is involved preferentially in nonvisually guided saccades using electrical stimulation. Monkeys performed visually guided and memory-guided saccades to locations throughout the visual field. On 50% of the trials, electrical stimulation of the SNr occurred. Stimulation of the SNr altered the direction, amplitude, latency, and probability of saccades. Visually guided saccades tended to be rotated toward the field contralateral to the side of stimulation, whereas memory-guided saccades tended to be rotated toward the hemifield ipsilateral to the side of stimulation. Overall, the changes in saccade vector direction were larger for memory-guided than for visually guided saccades. Both memory- and visually guided saccades were hypometric during stimulation trials, but the stimulation preferentially affected the length of memory-guided saccades. Electrical stimulation of the SNr produced decreases in visually guided saccades bilaterally. In contrast, memory-guided saccades often had increases in saccade latency bilaterally. Finally, we found approximately 10% reduction in the probability of memory-guided saccades bilaterally. Visually guided saccade probability was unaltered. Taken together the results are consistent with the hypothesis that SNr primarily influences nonvisually guided saccades. The pattern of stimulation effects suggests that SNr influence is widespread, altering the pattern of activity bilaterally across the superior colliculus map of saccades.

Temperature-dependent attenuation of ex-vessel flux measurements at the Hanford Fast Flux Test Facility

International Nuclear Information System (INIS)

McLane, F.E.; Wood, M.R.; Rathbun, J.L.

1982-01-01

Indicated nuclear power, developed by measuring leakage neutrons, has been found to be temperature dependent at the Hanford Fast Flux Test Facility (FFTF). The magnitude, sense and speed of response of the effect suggest that hot sodium above th core and shield is a significant cause. Future designs which may minimize this effect are discussed

Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

Science.gov (United States)

Ahn, Woo-Young; Vassileva, Jasmin

2016-04-01

Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of space-dependent cross sections on core physics parameters for compact fast spectrum space power reactors

International Nuclear Information System (INIS)

Lell, R.M.; Hanan, N.A.

1987-01-01

Effects of multigroup neutron cross section generation procedures on core physics parameters for compact fast spectrum reactors have been examined. Homogeneous and space-dependent multigroup cross section sets were generated in 11 and 27 groups for a representative fast reactor core. These cross sections were used to compute various reactor physics parameters for the reference core. Coarse group structure and neglect of space-dependence in the generation procedure resulted in inaccurate computations of reactor flux and power distributions and in significant errors regarding estimates of core reactivity and control system worth. Delayed neutron fraction was insensitive to cross section treatment, and computed reactivity coefficients were only slightly sensitive. However, neutron lifetime was found to be very sensitive to cross section treatment. Deficiencies in multigroup cross sections are reflected in core nuclear design and, consequently, in system mechanical design

Transcranial electric stimulation for intraoperative motor evoked potential monitoring: dependence of required stimulation current on interstimulus interval value.

Science.gov (United States)

Joksimovic, Boban; Szelenyi, Andrea; Seifert, Volker; Damjanovic, Aleksandar; Damjanovic, Aleksandra; Rasulic, Lukas

2015-05-01

To evaluate the relationship between stimulus intensity by constant current transcranial electric stimulation and interstimulus interval (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand muscles and the tibialis anterior muscles. We tested intraoperatively different monophasic constant current pulses and ISIs in 22 patients with clinically normal motor function. Motor thresholds of contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic constant current pulses of 62 to 104 mA before craniotomy and after closure of the dura mater. The lowest stimulation threshold to elicit MEPs in the examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before craniotomy, which was statistically significant compared with 2 pulses (ISI: 3 ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor thresholds with statistical significance compared with the ISIs of 4 ms (2 pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms) relationship graphs had a trend of the exponential function as y = a + bx + c ρ (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was determined for each patient and each muscle. The difference was statistically significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses and 2 and 5 pulses after closure of the dura mater. In adult neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI of 3 ms provide the lowest motor thresholds. We provided evidence of the dependence of required stimulation current on ISI. Georg Thieme Verlag KG Stuttgart · New York.

Differentiation-Dependent Motility-Responses of Developing Neural Progenitors to Optogenetic Stimulation

Directory of Open Access Journals (Sweden)

Tímea Köhidi

2017-12-01

Full Text Available During neural tissue genesis, neural stem/progenitor cells are exposed to bioelectric stimuli well before synaptogenesis and neural circuit formation. Fluctuations in the electrochemical potential in the vicinity of developing cells influence the genesis, migration and maturation of neuronal precursors. The complexity of the in vivo environment and the coexistence of various progenitor populations hinder the understanding of the significance of ionic/bioelectric stimuli in the early phases of neuronal differentiation. Using optogenetic stimulation, we investigated the in vitro motility responses of radial glia-like neural stem/progenitor populations to ionic stimuli. Radial glia-like neural stem cells were isolated from CAGloxpStoploxpChR2(H134-eYFP transgenic mouse embryos. After transfection with Cre-recombinase, ChR2(channelrhodopsin-2-expressing and non-expressing cells were separated by eYFP fluorescence. Expression of light-gated ion channels were checked by patch clamp and fluorescence intensity assays. Neurogenesis by ChR2-expressing and non-expressing cells was induced by withdrawal of EGF from the medium. Cells in different (stem cell, migrating progenitor and maturing precursor stages of development were illuminated with laser light (λ = 488 nm; 1.3 mW/mm2; 300 ms in every 5 min for 12 h. The displacement of the cells was analyzed on images taken at the end of each light pulse. Results demonstrated that the migratory activity decreased with the advancement of neuronal differentiation regardless of stimulation. Light-sensitive cells, however, responded on a differentiation-dependent way. In non-differentiated ChR2-expressing stem cell populations, the motility did not change significantly in response to light-stimulation. The displacement activity of migrating progenitors was enhanced, while the motility of differentiating neuronal precursors was markedly reduced by illumination.

Stimulating Creativity and Innovation through Intelligent Fast Failure

Science.gov (United States)

Tahirsylaj, Armend S.

2012-01-01

Literature on creativity and innovation has discussed the issue of failure in the light of its benefits and limitations for enhancing human potential in all domains of life, but in business, science, engineering, and industry more specifically. In this paper, the Intelligent Fast Failure (IFF) as a useful tool of creativity and innovation for…

Real‑time, fast neutron detection for stimulated safeguards assay

International Nuclear Information System (INIS)

Joyce, Malcolm J.; Adamczyk, Justyna; Plenteda, Romano; Aspinall, Michael D.; Cave, Francis D.

2015-01-01

The advent of low‑hazard organic liquid scintillation detectors and real‑time pulse‑shape discrimination (PSD) processing has suggested a variety of modalities by which fast neutrons, as opposed to neutrons moderated prior to detection, can be used directly to benefit safeguards needs. In this paper we describe a development of a fast‑neutron based safeguards assay system designed for the assessment of 235 U content in fresh fuel. The system benefits from real‑time pulse‑shape discrimination processing and auto‑calibration of the detector system parameters to ensure a rapid and effective set‑up protocol. These requirements are essential in optimising the speed and limit of detection of the fast neutron technique, whilst minimising the intervention needed to perform the assay.

Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data

Science.gov (United States)

2016-01-01

The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID:27548680

Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs.

Science.gov (United States)

Ponnath, Abhilash; Farris, Hamilton E

2014-01-01

Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound basis (ms), experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized) auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

Integrated wireless fast-scan cyclic voltammetry recording and electrical stimulation for reward-predictive learning in awake, freely moving rats

Science.gov (United States)

Li, Yu-Ting; Wickens, Jeffery R.; Huang, Yi-Ling; Pan, Wynn H. T.; Chen, Fu-Yu Beverly; Chen, Jia-Jin Jason

2013-08-01

Objective. Fast-scan cyclic voltammetry (FSCV) is commonly used to monitor phasic dopamine release, which is usually performed using tethered recording and for limited types of animal behavior. It is necessary to design a wireless dopamine sensing system for animal behavior experiments. Approach. This study integrates a wireless FSCV system for monitoring the dopamine signal in the ventral striatum with an electrical stimulator that induces biphasic current to excite dopaminergic neurons in awake freely moving rats. The measured dopamine signals are unidirectionally transmitted from the wireless FSCV module to the host unit. To reduce electrical artifacts, an optocoupler and a separate power are applied to isolate the FSCV system and electrical stimulator, which can be activated by an infrared controller. Main results. In the validation test, the wireless backpack system has similar performance in comparison with a conventional wired system and it does not significantly affect the locomotor activity of the rat. In the cocaine administration test, the maximum electrically elicited dopamine signals increased to around 230% of the initial value 20 min after the injection of 10 mg kg-1 cocaine. In a classical conditioning test, the dopamine signal in response to a cue increased to around 60 nM over 50 successive trials while the electrically evoked dopamine concentration decreased from about 90 to 50 nM in the maintenance phase. In contrast, the cue-evoked dopamine concentration progressively decreased and the electrically evoked dopamine was eliminated during the extinction phase. In the histological evaluation, there was little damage to brain tissue after five months chronic implantation of the stimulating electrode. Significance. We have developed an integrated wireless voltammetry system for measuring dopamine concentration and providing electrical stimulation. The developed wireless FSCV system is proven to be a useful experimental tool for the continuous

Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

Science.gov (United States)

Hanlon, C A; Dowdle, L T; Jones, J L

2016-01-01

Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). © 2016 Elsevier Inc. All rights reserved.

Kinetics of fast short-term depression are matched to spike train statistics to reduce noise.

Science.gov (United States)

Khanbabaie, Reza; Nesse, William H; Longtin, Andre; Maler, Leonard

2010-06-01

Short-term depression (STD) is observed at many synapses of the CNS and is important for diverse computations. We have discovered a form of fast STD (FSTD) in the synaptic responses of pyramidal cells evoked by stimulation of their electrosensory afferent fibers (P-units). The dynamics of the FSTD are matched to the mean and variance of natural P-unit discharge. FSTD exhibits switch-like behavior in that it is immediately activated with stimulus intervals near the mean interspike interval (ISI) of P-units (approximately 5 ms) and recovers immediately after stimulation with the slightly longer intervals (>7.5 ms) that also occur during P-unit natural and evoked discharge patterns. Remarkably, the magnitude of evoked excitatory postsynaptic potentials appear to depend only on the duration of the previous ISI. Our theoretical analysis suggests that FSTD can serve as a mechanism for noise reduction. Because the kinetics of depression are as fast as the natural spike statistics, this role is distinct from previously ascribed functional roles of STD in gain modulation, synchrony detection or as a temporal filter.

Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data

Directory of Open Access Journals (Sweden)

Tomasz Dzida

2017-09-01

Full Text Available We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα, RNA polymerase (Pol II and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle

DEFF Research Database (Denmark)

Gaster, M; Poulsen, P; Handberg, A

2000-01-01

GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8...... of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers....

NAD+-dependent HDAC inhibitor stimulates Monascus pigment production but inhibit citrinin.

Science.gov (United States)

Hu, Yan; Zhou, Youxiang; Mao, Zejing; Li, Huihui; Chen, Fusheng; Shao, Yanchun

2017-08-23

Monascus species are edible fungi due to the production of food colorant and other beneficial compounds. Hence, it has been an attractive thesis to improve their productivities. Increasing numbers of investigations revealed that regulating the activities of histone deacetylases can significantly perturb secondary metabolites (SM) production at a global level. In this study, dihydrocoumarin (DHC, an inhibitor of the Sirtuin family of NAD + -dependent deacetylases) was used to treat Monascus ruber for evaluating its effects on organism growth and SM production. The results revealed that the variation trends of colonial sizes, biomass and mycotoxin were in a dose-dependent manner. Generally, they decreased with the increased DHC concentrations in the designed range. But the variation trend of pigment was different. Comparison of SM profile, three new peaks occurred to the mycelia extractions from DHC-treated strain corresponding to molecular weights 402, 416 and 444, respectively. These three compounds were identified as Monasfluol B, Monascus azaphilone C and acetyl-monasfluol B (a new Monascus chemical pigment structure). In short, DHC can stimulate M. ruber strain to produce more pigment-like polyketides but inhibition of mycotoxin (citrinin).

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

DEFF Research Database (Denmark)

Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

2008-01-01

AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho......-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of c......AMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response....

A fast and flexible reactor physics model for simulating neutron spectra and depletion in fast reactors - 202

International Nuclear Information System (INIS)

Recktenwald, G.D.; Bronk, L.A.; Deinert, M.R.

2010-01-01

Determining the time dependent concentration of isotopes within a nuclear reactor core is central to the analysis of nuclear fuel cycles. We present a fast, flexible tool for determining the time dependent neutron spectrum within fast reactors. The code (VBUDS: visualization, burnup, depletion and spectra) uses a two region, multigroup collision probability model to simulate the energy dependent neutron flux and tracks the buildup and burnout of 24 actinides, as well as fission products. While originally developed for LWR simulations, the model is shown to produce fast reactor spectra that show high degree of fidelity to available fast reactor benchmarks. (authors)

Stimulation and inhibition of bacterial growth by caffeine dependent on chloramphenicol and a phenolic uncoupler--a ternary toxicity study using microfluid segment technique.

Science.gov (United States)

Cao, Jialan; Kürsten, Dana; Schneider, Steffen; Köhler, J Michael

2012-10-01

A droplet-based microfluidic technique for the fast generation of three dimensional concentration spaces within nanoliter segments was introduced. The technique was applied for the evaluation of the effect of two selected antibiotic substances on the toxicity and activation of bacterial growth by caffeine. Therefore a three-dimensional concentration space was completely addressed by generating large sequences with about 1150 well separated microdroplets containing 216 different combinations of concentrations. To evaluate the toxicity of the ternary mixtures a time-resolved miniaturized optical double endpoint detection unit using a microflow-through fluorimeter and a two channel microflow-through photometer was used for the simultaneous analysis of changes on the endogenous cellular fluorescence signal and on the cell density of E. coli cultivated inside 500 nL microfluid segments. Both endpoints supplied similar results for the dose related cellular response. Strong non-linear combination effects, concentration dependent stimulation and the formation of activity summits on bolographic maps were determined. The results reflect a complex response of growing bacterial cultures in dependence on the combined effectors. A strong caffeine induced enhancement of bacterial growth was found at sublethal chloramphenicol and sublethal 2,4-dinitrophenol concentrations. The reliability of the method was proved by a high redundancy of fluidic experiments. The results indicate the importance of multi-parameter investigations for toxicological studies and prove the potential of the microsegmented flow technique for such requirements.

Shared Neural Mechanisms for the Evaluation of Intense Sensory Stimulation and Economic Reward, Dependent on Stimulation-Seeking Behavior.

Science.gov (United States)

Norbury, Agnes; Valton, Vincent; Rees, Geraint; Roiser, Jonathan P; Husain, Masud

2016-09-28

Why are some people strongly motivated by intense sensory experiences? Here we investigated how people encode the value of an intense sensory experience compared with economic reward, and how this varies according to stimulation-seeking preference. Specifically, we used a novel behavioral task in combination with computational modeling to derive the value individuals assigned to the opportunity to experience an intense tactile stimulus (mild electric shock). We then examined functional imaging data recorded during task performance to see how the opportunity to experience the sensory stimulus was encoded in stimulation-seekers versus stimulation-avoiders. We found that for individuals who positively sought out this kind of sensory stimulation, there was common encoding of anticipated economic and sensory rewards in the ventromedial prefrontal cortex. Conversely, there was robust encoding of the modeled probability of receiving such stimulation in the insula only in stimulation-avoidant individuals. Finally, we found preliminary evidence that sensory prediction error signals may be positively signed for stimulation-seekers, but negatively signed for stimulation-avoiders, in the posterior cingulate cortex. These findings may help explain why high intensity sensory experiences are appetitive for some individuals, but not for others, and may have relevance for the increased vulnerability for some psychopathologies, but perhaps increased resilience for others, in high sensation-seeking individuals. People vary in their preference for intense sensory experiences. Here, we investigated how different individuals evaluate the prospect of an unusual sensory experience (electric shock), compared with the opportunity to gain a more traditional reward (money). We found that in a subset of individuals who sought out such unusual sensory stimulation, anticipation of the sensory outcome was encoded in the same way as that of monetary gain, in the ventromedial prefrontal cortex

Iron mediates N-methyl-D-aspartate receptor-dependent stimulation of calcium-induced pathways and hippocampal synaptic plasticity.

Science.gov (United States)

Muñoz, Pablo; Humeres, Alexis; Elgueta, Claudio; Kirkwood, Alfredo; Hidalgo, Cecilia; Núñez, Marco T

2011-04-15

Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-D-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP.

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

Science.gov (United States)

Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

2016-05-01

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

Fast online simultaneous monitoring of PMD and chromatic dispersion with reduced polarization dependent gain

Science.gov (United States)

Ning, G.; Shum, P.; Aditya, S.; Gong, Yandong

2006-09-01

We use the expression relating the output state of polarization and PMD vector. Based on this expression we get the power fading including first-order PMD and chromatic dispersion, which is dependent on the angle of precession of output state of polarization around the PMD vector. From the expression for power fading, we get the average power penalty for chromatic dispersion and PMD. We propose a novel and fast PMD and chromatic dispersion monitoring technology. Measured results agree well with theoretical analysis.

Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

DEFF Research Database (Denmark)

Kolnes, Anders J; Birk, Jesper Bratz; Eilertsen, Einar

2015-01-01

Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated...... in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating...... adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); pglycogen (89.5±7.6 vs 152.6±8.1 mmol•kg(-1); pglycogen (90.0±5.0 vs 102.8±7.8 mmol•kg(-1); p=0...

Time dependent start-up thermal analysis of a Super Fast Reactor

Energy Technology Data Exchange (ETDEWEB)

Sutanto,, E-mail: sutanto@fuji.waseda.jp; Oka, Yoshiaki

2013-10-15

Highlights: • Time dependent startup thermal analysis of a Super Fast Reactor is performed. • A recirculation system is used for pressurization and for generating supercritical steam. • MCST satisfies the criterion both during subcritical pressure and during power-raising. • MCST is not sensitive to the change of inlet temperature, gap volume and flow rate because of high flow to power ratio. • CHF is not limiting the MCST during subcritical pressure due to large margin of heat flux. -- Abstract: The startup system of a supercritical pressure light water cooled fast reactor (Super FR) is studied by time dependent thermal-hydraulic analysis. The plant analysis code is developed based on an innovative upward flow pattern in all the assemblies of the Super FR. A recirculation system consisting of a steam drum, a circulation pump, and a heat exchanger is used for the startup. Detailed procedures are performed and the maximum cladding surface temperature (MCST) at rated power, 640 °C, is used as the criterion. Firstly a small constant nuclear power is used for rising the core feed water temperature to be 280 °C through the recirculation system. Secondly, pressurization is done in the recirculation system from atmospheric to operating pressure, 25 MPa, by raising the power. Thirdly, line-switching from recirculation mode to once-through direct-cycle is performed while turbines are started by supercritical steam at supercritical pressure. Finally the power is raised to be 100% of power followed by raising the flow rate. During pressurization the heat flux margin is large due to low power used for pressurization and the MCST is much lower than the criterion. The MCST is not sensitive to the inlet temperature, the flow rate, and the gap volume of the core because of high flow to power ratio. Smaller dimension of steam drum can be used for pressurization stably. The MCST satisfies the criterion both during subcritical pressure and during power-raising.

Time dependent start-up thermal analysis of a Super Fast Reactor

International Nuclear Information System (INIS)

Sutanto,; Oka, Yoshiaki

2013-01-01

Highlights: • Time dependent startup thermal analysis of a Super Fast Reactor is performed. • A recirculation system is used for pressurization and for generating supercritical steam. • MCST satisfies the criterion both during subcritical pressure and during power-raising. • MCST is not sensitive to the change of inlet temperature, gap volume and flow rate because of high flow to power ratio. • CHF is not limiting the MCST during subcritical pressure due to large margin of heat flux. -- Abstract: The startup system of a supercritical pressure light water cooled fast reactor (Super FR) is studied by time dependent thermal-hydraulic analysis. The plant analysis code is developed based on an innovative upward flow pattern in all the assemblies of the Super FR. A recirculation system consisting of a steam drum, a circulation pump, and a heat exchanger is used for the startup. Detailed procedures are performed and the maximum cladding surface temperature (MCST) at rated power, 640 °C, is used as the criterion. Firstly a small constant nuclear power is used for rising the core feed water temperature to be 280 °C through the recirculation system. Secondly, pressurization is done in the recirculation system from atmospheric to operating pressure, 25 MPa, by raising the power. Thirdly, line-switching from recirculation mode to once-through direct-cycle is performed while turbines are started by supercritical steam at supercritical pressure. Finally the power is raised to be 100% of power followed by raising the flow rate. During pressurization the heat flux margin is large due to low power used for pressurization and the MCST is much lower than the criterion. The MCST is not sensitive to the inlet temperature, the flow rate, and the gap volume of the core because of high flow to power ratio. Smaller dimension of steam drum can be used for pressurization stably. The MCST satisfies the criterion both during subcritical pressure and during power-raising

Gravity dependence of the effect of optokinetic stimulation on the subjective visual vertical.

Science.gov (United States)

Ward, Bryan K; Bockisch, Christopher J; Caramia, Nicoletta; Bertolini, Giovanni; Tarnutzer, Alexander Andrea

2017-05-01

Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual, and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll angle. We hypothesized that the weights of vestibular (otolithic) and extravestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extravestibular cues with increasing roll angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll positions (≤ ± 120°, steps = 30°, n = 10) with/without presenting an optokinetic stimulus (velocity = ± 60°/s). The optokinetic stimulus biased the SVV toward the direction of stimulus rotation for roll angles ≥ ± 30° ( P stimulation. Variability and optokinetic bias were correlated ( R 2 = 0.71, slope = 0.71, 95% confidence interval = 0.57-0.86). An optimal-observer model combining an optokinetic bias with vestibular input reproduced measured errors closely. These findings support the hypothesis of a weighted multisensory integration when estimating direction of gravity with optokinetic stimulation. Visual input was weighted more when vestibular input became less reliable, i.e., at larger roll-tilt angles. However, according to Bayesian theory, the variability of combined cues is always lower than the variability of each source cue. If the observed increase in variability, although nonsignificant, is true, either it must depend on an additional source of variability, added after SVV computation, or it would conflict with the Bayesian hypothesis. NEW & NOTEWORTHY Applying a rotating optokinetic stimulus while recording the subjective visual vertical in different whole body roll angles, we noted the optokinetic

ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells.

Science.gov (United States)

Furumatsu, Takayuki; Maehara, Ami; Ozaki, Toshifumi

2016-07-01

Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells. Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed. Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment. This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation

Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

Science.gov (United States)

Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

2013-04-01

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

International Nuclear Information System (INIS)

Mu, Shumin; Tian, Xingsong; Ruan, Yongwei; Liu, Yuantao; Bian, Dezhi; Ma, Chunyan; Yu, Chunxiao; Feng, Mei; Wang, Furong; Gao, Ling; Zhao, Jia-jun

2012-01-01

Highlights: ► Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. ► Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. ► Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

DEFF Research Database (Denmark)

Richter, Erik; Hansen, S A; Hansen, B F

1988-01-01

increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean +/- SE) from 34.9 +/- 1.2 mumol.g-1.h-1 at 0 h to 7.5 +/- 0.7 after 7 h of perfusion. During...... compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal....

Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

Science.gov (United States)

Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

2014-01-01

Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

Elasticity-dependent fast underwater adhesion demonstrated by macroscopic supramolecular assembly.

Science.gov (United States)

Ju, Guannan; Cheng, Mengjiao; Guo, Fengli; Zhang, Qian; Shi, Feng

2018-05-30

Macroscopic supramolecular assembly (MSA) is a recent progress in supramolecular chemistry to associate visible building blocks through non-covalent interactions in a multivalent manner. Although various substrates (e. g. hydrogels, rigid materials) have been used, a general design rule of building blocks in MSA systems and interpretation of the assembly mechanism are still lacking and urgently in demand. Here we design three model systems with varied modulus and correlated the MSA probability with the elasticity. Based on the effects of substrate deformability on multivalency, we have proposed an elastic-modulus-dependent rule that building blocks below a critical modulus of 2.5 MPa can achieve MSA for the used host/guest system. Moreover, this MSA rule applies well to the design of materials applicable for fast underwater adhesion: Soft substrates (0.5 MPa) can achieve underwater adhesion within 10 s with one magnitude higher strength than that of rigid substrates (2.5 MPa). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intensity dependent waiting time for strong electron trapping events in speckle stimulated raman scatter

Energy Technology Data Exchange (ETDEWEB)

Rose, Harvey [Los Alamos National Laboratory; Daughton, W [Los Alamos National Laboratory; Yin, L [Los Alamos National Laboratory

2009-01-01

The onset of Stimulated Raman scatter from an intense laser speckle is the simplest experimentally realizable laser-plasma-interaction environment. Despite this data and recent 3D particle simulations, the controlling mechanism at the onset of backscatter in the kinetic regime when strong electron trapping in the daughter Langmuir wave is a dominant nonlinearity is not understood. This paper explores the consequences of assuming that onset is controlled by large thermal fluctuations. A super exponential dependence of mean reflectivity on speckle intensity in the onset regime is predicted.

Influence of gamma radiation and fast neutrons on the growth of Haplopappus gracilis (Nutt) A. Gray callus

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Wajda, L.; Korzonek, M.; Polska Akademia Nauk, Krakow. Inst. Fizjologii Roslin)

1979-01-01

The sensitivity of the callus of Haplopappus gracilis to gamma radiation and fast neutrons was studied. High doses of radiation cause inhibition of callus growth. At small doses the effect is less pronounced. Stimulation of callus growth was seen. Apart from morphological changes, ionizing radiations lowered the fresh weight ratio of the callus. The RBE value for 5.5 MeV neutrons depended on the dose rate of radiation and the combination of growth medium. (author)

CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

Science.gov (United States)

Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

2015-04-01

The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

Energy dependence of fast neutron dosimetry using electrochemical etching

International Nuclear Information System (INIS)

Su, S.J.; Morgan, K.Z.

1978-01-01

Registration of fast-neutron induced recoil tracks by the electrochemical etching technique as applied to sensitive Lexan polycarbonate foils provides a simple and inexpensive means of fast neutron personnel dosimetry. The sensitivity (tracks/neutron) of recoil particle registration is given as a function of neutron energy. Neutrons of 7 Li (p,n) 7 Be, 3 T (d,n) 4 He and 9 B, respectively. Results are compared with other studies using other neutron sources and conventional etching method

Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

Science.gov (United States)

Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

2014-01-01

Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

Does Childhood Use of Stimulant Medication as a Treatment for ADHD Affect the Likelihood of Future Drug Abuse and Dependence? A Literature Review

Science.gov (United States)

Golden, Shawn M.

2009-01-01

This article describes the disparate research findings regarding the effects of stimulant medication in subsequent substance abuse and dependence. A minimum of 4 to 5% of children in the United States will be diagnosed with ADHD; thus it is important for parents to be informed when making decisions about the use of stimulant medication to treat…

Fast ignition: Dependence of the ignition energy on source and target parameters for particle-in-cell-modelled energy and angular distributions of the fast electrons

Energy Technology Data Exchange (ETDEWEB)

Bellei, C.; Divol, L.; Kemp, A. J.; Key, M. H.; Larson, D. J.; Strozzi, D. J.; Marinak, M. M.; Tabak, M.; Patel, P. K. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States)

2013-05-15

The energy and angular distributions of the fast electrons predicted by particle-in-cell (PIC) simulations differ from those historically assumed in ignition designs of the fast ignition scheme. Using a particular 3D PIC calculation, we show how the ignition energy varies as a function of source-fuel distance, source size, and density of the pre-compressed fuel. The large divergence of the electron beam implies that the ignition energy scales with density more weakly than the ρ{sup −2} scaling for an idealized beam [S. Atzeni, Phys. Plasmas 6, 3316 (1999)], for any realistic source that is at some distance from the dense deuterium-tritium fuel. Due to the strong dependence of ignition energy with source-fuel distance, the use of magnetic or electric fields seems essential for the purpose of decreasing the ignition energy.

Glucose turnover in 48-hour-fasted running rats

International Nuclear Information System (INIS)

Sonne, B.; Mikines, K.J.; Galbo, H.

1987-01-01

In fed rats, hyperglycemia develops during exercise. This contrasts with the view based on studies of fasted human and dog that euglycemia is maintained in exercise and glucose production (R/sub a/) controlled by feedback mechanisms. Forty-eight-hour-fasted rats (F) were compared to fed rats (C) and overnight food-restricted (FR) rats. [3- 3 H]- and [U- 14 C]glucose were infused and blood and tissue sampled. During running (21 m/min, 0% grade) R/sub a/ increased most in C and least in F and only in F did R/sub a/ not significantly exceed glucose disappearance. Plasma glucose increased more in C (3.3 mmol/1) than in FR (1.6 mmol/l) and only modestly (0.6 mmol/l) and transiently in F. Resting liver glycogen and exercise glycogenolysis were highest in C and similar in FR and F. Resting muscle glycogen and exercise glycogenolysis were highest in C and lowest in F. During running, lactate production and gluconeogenesis were higher in FR than in F. At least in rats, responses of production and plasma concentration of glucose to exercise depend on size of liver and muscle glycogen stores; glucose production matches increase in clearance better in fasted than in fed states. Probably glucose production is stimulated by feedforward mechanisms and feedback mechanisms are added if plasma glucose decreases

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

Energy Technology Data Exchange (ETDEWEB)

Mu, Shumin [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan 250011 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Tian, Xingsong; Ruan, Yongwei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Liu, Yuantao [The Second Hospital of Shandong University, Jinan 250033 (China); Bian, Dezhi [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Jining Medical College, Jining 272013 (China); Ma, Chunyan [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Yu, Chunxiao [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Feng, Mei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Wang, Furong [Shandong University of Traditional Chinese Medicine, Jinan 250011 (China); Gao, Ling [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Zhao, Jia-jun, E-mail: jjzhao@medmail.com.cn [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China)

2012-02-10

Highlights: Black-Right-Pointing-Pointer Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. Black-Right-Pointing-Pointer Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. Black-Right-Pointing-Pointer Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

The calculation of site-dependent earthquake motions -3. The method of fast fourier transform

International Nuclear Information System (INIS)

Simpson, I.C.

1976-10-01

The method of Fast Fourier transform (FFT) is applied to the problem of the determination of site-dependent earthquake motions, which takes account of local geological effects. A program, VELAY 1, which uses the FFT method has been written and is described in this report. The assumptions of horizontally stratified, homogeneous, isotropic, linearly viscoelastic layers and a normally incident plane seismic wave are made. Several examples are given, using VELAY 1, of modified surface acceleration-time histories obtained using a selected input acceleration-time history and a representative system of soil layers. There is a discussion concerning the soil properties that need to be measured in order to use VELAY 1 (and similar programs described in previous reports) and hence generate site-dependent ground motions suitable for aseismic design of a nuclear power plant at a given site. (author)

Fast simulation of reconstructed phylogenies under global time-dependent birth-death processes.

Science.gov (United States)

Höhna, Sebastian

2013-06-01

Diversification rates and patterns may be inferred from reconstructed phylogenies. Both the time-dependent and the diversity-dependent birth-death process can produce the same observed patterns of diversity over time. To develop and test new models describing the macro-evolutionary process of diversification, generic and fast algorithms to simulate under these models are necessary. Simulations are not only important for testing and developing models but play an influential role in the assessment of model fit. In the present article, I consider as the model a global time-dependent birth-death process where each species has the same rates but rates may vary over time. For this model, I derive the likelihood of the speciation times from a reconstructed phylogenetic tree and show that each speciation event is independent and identically distributed. This fact can be used to simulate efficiently reconstructed phylogenetic trees when conditioning on the number of species, the time of the process or both. I show the usability of the simulation by approximating the posterior predictive distribution of a birth-death process with decreasing diversification rates applied on a published bird phylogeny (family Cettiidae). The methods described in this manuscript are implemented in the R package TESS, available from the repository CRAN (http://cran.r-project.org/web/packages/TESS/). Supplementary data are available at Bioinformatics online.

Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction.

Science.gov (United States)

Steiner, Jennifer L; Lang, Charles H

2014-11-15

Alcohol (EtOH) decreases protein synthesis and mammalian target of rapamycin (mTOR)-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle. The purpose of the current investigation was to determine whether acute EtOH intoxication antagonizes the contraction-induced increase in protein synthesis and mTOR signaling in skeletal muscle. Fasted male mice were injected intraperitoneally with 3 g/kg EtOH or saline (control), and the right hindlimb was electrically stimulated (10 sets of 6 contractions). The gastrocnemius muscle complex was collected 30 min, 4 h, or 12 h after stimulation. EtOH decreased in vivo basal protein synthesis (PS) in the nonstimulated muscle compared with time-matched Controls at 30 min, 4 h, and 12 h. In Control, but not EtOH, PS was decreased 15% after 30 min. In contrast, PS was increased in Control 4 h poststimulation but remained unchanged in EtOH. Last, stimulation increased PS 10% in Control and EtOH at 12 h, even though the absolute rate remained reduced by EtOH. The stimulation-induced increase in the phosphorylation of S6K1 Thr(421)/Ser(424) (20-52%), S6K1 Thr(389) (45-57%), and its substrate rpS6 Ser(240/244) (37-72%) was blunted by EtOH at 30 min, 4 h, and 12 h. Phosphorylation of 4E-BP1 Ser(65) was also attenuated by EtOH (61%) at 4 h. Conversely, phosphorylation of extracellular signal-regulated kinase Thr(202)/Tyr(204) was increased by stimulation in Control and EtOH mice at 30 min but only in Control at 4 h. Our data indicate that acute EtOH intoxication suppresses muscle protein synthesis for at least 12 h and greatly impairs contraction-induced changes in synthesis and mTOR signaling. Copyright © 2014 the American Physiological Society.

Age-dependent effects of brain stimulation on network centrality.

Science.gov (United States)

Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus; Prehn, Kristin; Thielscher, Axel; Ittermann, Bernd; Flöel, Agnes

2018-04-18

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation were explained from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults. Copyright © 2018. Published by Elsevier Inc.

Frequency-time behavior of artificially stimulated vlf emissions

International Nuclear Information System (INIS)

Stiles, G.S.; Helliwell, R.A.

1975-01-01

Artificially stimulated VLF emissions (ASE's) are emissions triggered in the magnetosphere by the whistler mode signals from VLF transmitters. These emissions may be separated into two classes, rising and falling, depending on whether the final value of df/dt is positive or negative. Several hundred ASE's triggered by three transmitters have been analyzed using the fast Fourier transform with a filter spacing of 25 Hz and an effective filter width of about 45 Hz. The study was limited to the initial frequency-time behavior of ASE's. Averages taken over many events reveal that both rising and falling tones show the same initial behavior. The emissions begin at the frequency of the triggering signal. Both tones initially rise in frequency, falling tones reversing slope at a point 25--300 Hz above the triggering signal. The slope of rising tones, particularly those triggered by NAA, often abruptly levels off in this same frequency range; as a result, a short (approximately 40 ms) plateau is formed that precedes the final rising phase. The initial frequency offset commonly observed in individual events appears to result from the frequent coincidence with this plateau of a peak in amplitude. Emissions stimulated by all three transmitters show essentially the same features; this finding indicates that their frequency behavior does not depend strongly on transmitter power. The process appears to be asymmetric in frequency; no evidence of initial growth below the triggering frequency has been found. (U.S.)

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

Directory of Open Access Journals (Sweden)

Guoshi Li

2017-10-01

Full Text Available The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh and norepinephrine (NE and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

Science.gov (United States)

Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

2014-02-05

The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway.

Science.gov (United States)

Liu, Haiyan; Javaheri, Ali; Godar, Rebecca J; Murphy, John; Ma, Xiucui; Rohatgi, Nidhi; Mahadevan, Jana; Hyrc, Krzysztof; Saftig, Paul; Marshall, Connie; McDaniel, Michael L; Remedi, Maria S; Razani, Babak; Urano, Fumihiko; Diwan, Abhinav

2017-01-01

Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin 1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in nonobese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.

Interactions of cervico-ocular and vestibulo-ocular fast-phase signals in the control of eye position in rabbits.

Science.gov (United States)

Barmack, N H; Errico, P; Ferraresi, A; Pettorossi, V E

1989-01-01

1. Eye movements in unanaesthetized rabbits were studied during horizontal neck-proprioceptive stimulation (movement of the body with respect to the fixed head), when this stimulation was given alone and when it was given simultaneously with vestibular stimulation (rotation of the head-body). The effect of neck-proprioceptive stimulation on modifying the anticompensatory fast-phase eye movements (AFPs) evoked by vestibular stimulation was studied with a 'conditioning-test' protocol; the 'conditioning' stimulus was a neck-proprioceptive signal evoked by a step-like change in body position with respect to the head and the 'test' stimulus was a vestibular signal evoked by a step rotation of the head-body. 2. The influence of eye position and direction of slow eye movements on the occurrence of compensatory fast-phase eye movements (CFPs) evoked by neck-proprioceptive stimulation was also examined. 3. The anticompensatory fast phase (AFP) evoked by vestibular stimulation was attenuated by a preceding neck-proprioceptive stimulus which when delivered alone evoked compensatory slow-phase eye movements (CSP) in the same direction as the CSP evoked by vestibular stimulation. Conversely, the vestibularly evoked AFP was potentiated by a neck-proprioceptive stimulus which evoked CSPs opposite to that of vestibularly evoked CSPs. 4. Eccentric initial eye positions increased the probability of occurrence of midline-directed compensatory fast-phase eye movements (CFPs) evoked by appropriate neck-proprioceptive stimulation. 5. The gain of the horizontal cervico-ocular reflex (GHCOR) was measured from the combined changes in eye position resulting from AFPs and CSPs. GHCOR was potentiated during simultaneous vestibular stimulation. This enhancement of GHCOR occurred at neck-proprioceptive stimulus frequencies which, in the absence of conjoint vestibular stimulation, do not evoke CSPs. PMID:2795479

Stimulating at the right time: phase-specific deep brain stimulation.

Science.gov (United States)

Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

2017-01-01

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism

DEFF Research Database (Denmark)

Olsen, Hervør L; Nørby, Peder L; Høy, Marianne

2003-01-01

We have previously demonstrated that the novel imidazoline compound (+)-2-(2-(4,5-dihydro-1H-imidazol-2-yl)-thiopene-2-yl-ethyl)-pyridine (NNC77-0074) increases insulin secretion from pancreatic beta-cells by stimulation of Ca(2+)-dependent exocytosis. Using capacitance measurements, we now show...... that NNC77-0074 stimulates exocytosis in clonal INS-1E cells. NNC77-0074-stimulated exocytosis was antagonised by the cytoplasmic phospholipase A(2) (cPLA(2)) inhibitors ACA and AACOCF(3) and in cells treated with antisense oligonucleotide against cPLA(2)alpha. NNC77-0074-evoked insulin secretion...... was likewise inhibited by ACA, AACOCF(3), and cPLA(2)alpha antisense oligonucleotide treatment. In pancreatic islets NNC77-0074 stimulated PLA(2) activity. We propose that cPLA(2)alpha plays an important role in the regulation of NNC77-0074-evoked exocytosis in insulin secreting beta-cells....

Pulse and integral optically stimulated luminescence (OSL). Similarities and dissimilarities to thermoluminescence (TL) dose dependence and dose-rate effects

International Nuclear Information System (INIS)

Chen, R.; Leung, P.L.

2000-01-01

Optically stimulated luminescence (OSL) and thermoluminescence (Tl) are two possible methods to monitor the absorbed radiation in solid samples, and therefore are utilized for dosimetry. For this application, two properties are desirable, namely, linear dose dependence of the measured quantity and dose-rate independence. For Tl, different kinds of super linear dose dependence have been reported in the literature in different materials, and in some cases, dose-rate dependence has also been found. These have been explained as being the result of competition. In OSL, some recent works reported on super linear dose dependence in annealed samples. In the present work, we explain the possible occurrence of these phenomena in OSL by solving numerically the relevant rate equations governing the process during irradiation, relaxation and read-out (heating or light stimulation). The results show that for short pulse OSL, quadratic dose dependence can be expected when only one trapping state and one kind of recombination center are involved and when the excitation starts with empty traps and centers. With the short pulse OSL, the calculation also reveals a possible dose-rate effect. Under the same circumstances, the area under the OSL curve depends linearly on the dose. The dependence of the whole area under the OSL curve on the dose is shown to be super linear when a disconnected trapping state or radiationless center take part in the process. Also, dose-rate effect can be expected in these cases, although no experimental effect of this sort has been reported so far. In pulse OSL, the analogy is made between the measured intensity and the initial rise range of non-first order Tl, whereas for the total area OSL, there is a nearly full analogy with the dose behavior of the Tl maximum. (Author)

Size dependence study of the ordering temperature in the Fast Monte Carlo method

Energy Technology Data Exchange (ETDEWEB)

Velasquez, E. A., E-mail: eavelas@gmail.com [Universidad de San Buenaventura Seccional Medellin, Grupo de Investigacion en Modelamiento y Simulacion Computacional, Facultad de Ingenierias (Colombia); Mazo-Zuluaga, J., E-mail: johanmazo@gmail.com [Universidad de Antioquia, Grupo de Estado Solido, Grupo de Instrumentacion Cientifica y Microelectronica, Instituto de Fisica-FCEN (Colombia); Mejia-Lopez, J., E-mail: jmejia@puc.cl [Universidad de Antioquia, Instituto de Fisica-FCEN (Colombia)

2013-02-15

Based on the framework of the Fast Monte Carlo approach, we study the diameter dependence of the ordering temperature in magnetic nanostructures of cylindrical shape. For the purposes of this study, Fe cylindrical-shaped samples of different sizes (20 nm height, 30-100 nm in diameter) have been chosen, and their magnetic properties have been computed as functions of the scaled temperature. Two main set of results are concluded: (a) the ordering temperature of nanostructures follows a linear scaling relationship as a function of the scaling factor x, for all the studied sizes. This finding rules out a scaling relation T Prime {sub c} = x{sup 3{eta}}T{sub c} (where {eta} is a scaling exponent, and T Prime {sub c} and T{sub c} are the scaled and true ordering temperatures) that has been proposed in the literature, and suggests that temperature should scale linearly with the scaling factor x. (b) For the nanostructures, there are three different order-disorder magnetic transition modes depending on the system's size, in very good agreement with previous experimental reports.

Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1-dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

Science.gov (United States)

Dries, Eef; Santiago, Demetrio J; Johnson, Daniel M; Gilbert, Guillaume; Holemans, Patricia; Korte, Sanne M; Roderick, H Llewelyn; Sipido, Karin R

2016-10-15

The dyadic cleft, where coupled ryanodine receptors (RyRs) reside, is thought to serve as a microdomain for local signalling, as supported by distinct modulation of coupled RyRs dependent on Ca 2+ /calmodulin-dependent kinase II (CaMKII) activation during high-frequency stimulation. Sympathetic stimulation through β-adrenergic receptors activates an integrated signalling cascade, enhancing Ca 2+ cycling and is at least partially mediated through CaMKII. Here we report that CaMKII activation during β-adrenergic signalling is restricted to the dyadic cleft, where it enhances activity of coupled RyRs thereby contributing to the increase in diastolic events. Nitric oxide synthase 1 equally participates in the local modulation of coupled RyRs. In contrast, the increase in the Ca 2+ content of the sarcoplasmic reticulum and related increase in the amplitude of the Ca 2+ transient are primarily protein kinase A-dependent. The present data extend the concept of microdomain signalling in the dyadic cleft and give perspectives for selective modulation of RyR subpopulations and diastolic events. In cardiac myocytes, β-adrenergic stimulation enhances Ca 2+ cycling through an integrated signalling cascade modulating L-type Ca 2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca 2+ /calmodulin-dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca 2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca 2+ ] i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca 2+ sparks, which are assigned to coupled and non-coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca 2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces

Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

International Nuclear Information System (INIS)

Ryu, T.; Davis, J.M.; Schwartz, K.A.

1990-01-01

The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding

Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats

NARCIS (Netherlands)

Beuers, U.; JUNGERMANN, K.

1990-01-01

The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was

Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in hepatocytes.

Science.gov (United States)

Chen, Christine; Deng, Meihong; Sun, Qian; Loughran, Patricia; Billiar, Timothy R; Scott, Melanie J

2014-01-01

Impairment of autophagy has been associated with liver injury. TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive. The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR. Autophagy-like activation was measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NF κ B transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

DEFF Research Database (Denmark)

Friis, P; Svehag, S E; Andersen, Ove

1991-01-01

. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited......Conglutinin is a mammalian C-type lectin which shows anti-bacterial activity when tested in vivo and in vitro. This study concerns the effect of conglutinin on the respiratory burst of murine spleen cells, using a chemiluminescence assay for measurement of generated reactive oxygen metabolites...

A compact, multifunctional fusion module directs cholesterol-dependent homomultimerization and syncytiogenic efficiency of reovirus p10 FAST proteins.

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Tim Key

2014-03-01

Full Text Available The homologous p10 fusion-associated small transmembrane (FAST proteins of the avian (ARV and Nelson Bay (NBV reoviruses are the smallest known viral membrane fusion proteins, and are virulence determinants of the fusogenic reoviruses. The small size of FAST proteins is incompatible with the paradigmatic membrane fusion pathway proposed for enveloped viral fusion proteins. Understanding how these diminutive viral fusogens mediate the complex process of membrane fusion is therefore of considerable interest, from both the pathogenesis and mechanism-of-action perspectives. Using chimeric ARV/NBV p10 constructs, the 36-40-residue ectodomain was identified as the major determinant of the differing fusion efficiencies of these homologous p10 proteins. Extensive mutagenic analysis determined the ectodomain comprises two distinct, essential functional motifs. Syncytiogenesis assays, thiol-specific surface biotinylation, and liposome lipid mixing assays identified an ∼25-residue, N-terminal motif that dictates formation of a cystine loop fusion peptide in both ARV and NBV p10. Surface immunofluorescence staining, FRET analysis and cholesterol depletion/repletion studies determined the cystine loop motif is connected through a two-residue linker to a 13-residue membrane-proximal ectodomain region (MPER. The MPER constitutes a second, independent motif governing reversible, cholesterol-dependent assembly of p10 multimers in the plasma membrane. Results further indicate that: (1 ARV and NBV homomultimers segregate to distinct, cholesterol-dependent microdomains in the plasma membrane; (2 p10 homomultimerization and cholesterol-dependent microdomain localization are co-dependent; and (3 the four juxtamembrane MPER residues present in the multimerization motif dictate species-specific microdomain association and homomultimerization. The p10 ectodomain therefore constitutes a remarkably compact, multifunctional fusion module that directs syncytiogenic

GPR39 signaling is stimulated by zinc ions but not by obestatin

DEFF Research Database (Denmark)

Holst, Birgitte; Egerod, Kristoffer L; Schild, Enrico

2006-01-01

GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be the receptor for obestatin, a peptide derived from the ghrelin precursor. Here, we compare the effect of obestatin to the effect of Zn(2+) on signal transduction and study the effect of obestatin on food...... intake. Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect...... organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin. Obestatin had no significant and reproducible effect on acute food intake in either freely fed or fasted lean mice. It is concluded that GPR39 is probably not the obestatin...

Impacts of burnup-dependent swelling of metallic fuel on the performance of a compact breed-and-burn fast reactor

Energy Technology Data Exchange (ETDEWEB)

Hartanto, Donny; Heo, Woong; Kim, Chi Hyung; Kim, Yong Hee [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon (Korea, Republic of)

2016-04-15

The U-Zr or U-TRU-Zr cylindrical metallic fuel slug used in fast reactors is known to swell significantly and to grow during irradiation. In neutronics simulations of metallic-fueled fast reactors, it is assumed that the slug has swollen and contacted cladding, and the bonding sodium has been removed from the fuel region. In this research, a realistic burnup-dependent fuel-swelling simulation was performed using Monte Carlo code McCARD for a single-batch compact sodium-cooled breed-and-burn reactor by considering the fuel-swelling behavior reported from the irradiation test results in EBR-II. The impacts of the realistic burnup-dependent fuel swelling are identified in terms of the reactor neutronics performance, such as core lifetime, conversion ratio, axial power distribution, and local burnup distributions. It was found that axial fuel growth significantly deteriorated the neutron economy of a breed-and-burn reactor and consequently impaired its neutronics performance. The bonding sodium also impaired neutron economy, because it stayed longer in the blanket region until the fuel slug reached 2% burnup.

Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

Science.gov (United States)

Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

2016-04-01

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chenodeoxycholic acid stimulated fibroblast growth factor 19 response

DEFF Research Database (Denmark)

Borup, C; Wildt, S; Rumessen, J J

2017-01-01

BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid...

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

Science.gov (United States)

Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease.

Science.gov (United States)

Ciampi de Andrade, Daniel; Lefaucheur, Jean-Pascal; Galhardoni, Ricardo; Ferreira, Karine S L; Brandão Paiva, Anderson Rodrigues; Bor-Seng-Shu, Edson; Alvarenga, Luciana; Myczkowski, Martin L; Marcolin, Marco Antonio; de Siqueira, Silvia R D T; Fonoff, Erich; Barbosa, Egberto Reis; Teixeira, Manoel Jacobsen

2012-05-01

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P=.019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Modeling of the shape of infrared stimulated luminescence signals in feldspars

DEFF Research Database (Denmark)

Pagonis, Vasilis; Jain, Mayank; Murray, Andrew S.

2012-01-01

This paper presents a new empirical model describing infrared (IR) stimulation phenomena in feldspars. In the model electrons from the ground state of an electron trap are raised by infrared optical stimulation to the excited state, and subsequently recombine with a nearest-neighbor hole via...... corresponds to a fast rate of recombination processes taking place along the infrared stimulated luminescence (IRSL) curves. The subsequent decay of the simulated IRSL signal is characterized by a much slower recombination rate, which can be described by a power-law type of equation.Several simulations...

Contact- and Protein Transfer-Dependent Stimulation of Assembly of the Gliding Motility Machinery in Myxococcus xanthus.

Directory of Open Access Journals (Sweden)

Beata Jakobczak

2015-07-01

Full Text Available Bacteria engage in contact-dependent activities to coordinate cellular activities that aid their survival. Cells of Myxococcus xanthus move over surfaces by means of type IV pili and gliding motility. Upon direct contact, cells physically exchange outer membrane (OM lipoproteins, and this transfer can rescue motility in mutants lacking lipoproteins required for motility. The mechanism of gliding motility and its stimulation by transferred OM lipoproteins remain poorly characterized. We investigated the function of CglC, GltB, GltA and GltC, all of which are required for gliding. We demonstrate that CglC is an OM lipoprotein, GltB and GltA are integral OM β-barrel proteins, and GltC is a soluble periplasmic protein. GltB and GltA are mutually stabilizing, and both are required to stabilize GltC, whereas CglC accumulate independently of GltB, GltA and GltC. Consistently, purified GltB, GltA and GltC proteins interact in all pair-wise combinations. Using active fluorescently-tagged fusion proteins, we demonstrate that GltB, GltA and GltC are integral components of the gliding motility complex. Incorporation of GltB and GltA into this complex depends on CglC and GltC as well as on the cytoplasmic AglZ protein and the inner membrane protein AglQ, both of which are components of the gliding motility complex. Conversely, incorporation of AglZ and AglQ into the gliding motility complex depends on CglC, GltB, GltA and GltC. Remarkably, physical transfer of the OM lipoprotein CglC to a ΔcglC recipient stimulates assembly of the gliding motility complex in the recipient likely by facilitating the OM integration of GltB and GltA. These data provide evidence that the gliding motility complex in M. xanthus includes OM proteins and suggest that this complex extends from the cytoplasm across the cell envelope to the OM. These data add assembly of gliding motility complexes in M. xanthus to the growing list of contact-dependent activities in bacteria.

Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission.

Science.gov (United States)

Leung, Albert; Shukla, Shivshil; Lee, Jacquelyn; Metzger-Smith, Valerie; He, Yifan; Chen, Jeffrey; Golshan, Shahrokh

2015-09-01

Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers. © 2015 Wiley Periodicals, Inc.

Sparse-sampling with time-encoded (TICO) stimulated Raman scattering for fast image acquisition

Science.gov (United States)

Hakert, Hubertus; Eibl, Matthias; Karpf, Sebastian; Huber, Robert

2017-07-01

Modern biomedical imaging modalities aim to provide researchers a multimodal contrast for a deeper insight into a specimen under investigation. A very promising technique is stimulated Raman scattering (SRS) microscopy, which can unveil the chemical composition of a sample with a very high specificity. Although the signal intensities are enhanced manifold to achieve a faster acquisition of images if compared to standard Raman microscopy, there is a trade-off between specificity and acquisition speed. Commonly used SRS concepts either probe only very few Raman transitions as the tuning of the applied laser sources is complicated or record whole spectra with a spectrometer based setup. While the first approach is fast, it reduces the specificity and the spectrometer approach records whole spectra -with energy differences where no Raman information is present-, which limits the acquisition speed. Therefore, we present a new approach based on the TICO-Raman concept, which we call sparse-sampling. The TICO-sparse-sampling setup is fully electronically controllable and allows probing of only the characteristic peaks of a Raman spectrum instead of always acquiring a whole spectrum. By reducing the spectral points to the relevant peaks, the acquisition time can be greatly reduced compared to a uniformly, equidistantly sampled Raman spectrum while the specificity and the signal to noise ratio (SNR) are maintained. Furthermore, all laser sources are completely fiber based. The synchronized detection enables a full resolution of the Raman signal, whereas the analogue and digital balancing allows shot noise limited detection. First imaging results with polystyrene (PS) and polymethylmethacrylate (PMMA) beads confirm the advantages of TICO sparse-sampling. We achieved a pixel dwell time as low as 35 μs for an image differentiating both species. The mechanical properties of the applied voice coil stage for scanning the sample currently limits even faster acquisition.

Effects of fast neutrons on chromatin: dependence on chromatin structure

Energy Technology Data Exchange (ETDEWEB)

Radu, L. [Dept. of Molecular Genetics, V. Babes National Inst., Bd. Timisoara, Bucharest (Romania); Constantinescu, B. [Dept. of Cyclotron, H. Hulubei National Inst., Bucharest (Romania); Gazdaru, D. [Dept. of Biophysics, Physics Faculty, Univ. of Bucharest (Romania)

2002-07-01

The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin-proflavine complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl chloride and acridine orange coupled to chromatin. For both normal and tumor chromatin, the intensity of intrinsic fluorescence specific for acidic and basic proteins decreased with increasing dose. The relative contributions of the excited-state lifetime of proflavine bound to chromatin were reduced upon fast-neutron irradiation, indicating a decrease in the proportion of chromatin DNA available for ligand binding. The Forster energy transfer efficiencies were also modified by irradiation. These effects were larger for chromatin from tumor tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and acidic and basic proteins, as well as in global chromatin structure. The radiosensitivity of chromatin extracted from tumor tissue seems to be higher than that of chromatin extracted from normal tissue, probably because of its higher euchromatin (loose)-heterochromatin (compact) ratio. (author)

Effects of fast neutrons on chromatin: dependence on chromatin structure

International Nuclear Information System (INIS)

Radu, L.; Constantinescu, B.; Gazdaru, D.

2002-01-01

The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin-proflavine complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl chloride and acridine orange coupled to chromatin. For both normal and tumor chromatin, the intensity of intrinsic fluorescence specific for acidic and basic proteins decreased with increasing dose. The relative contributions of the excited-state lifetime of proflavine bound to chromatin were reduced upon fast-neutron irradiation, indicating a decrease in the proportion of chromatin DNA available for ligand binding. The Forster energy transfer efficiencies were also modified by irradiation. These effects were larger for chromatin from tumor tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and acidic and basic proteins, as well as in global chromatin structure. The radiosensitivity of chromatin extracted from tumor tissue seems to be higher than that of chromatin extracted from normal tissue, probably because of its higher euchromatin (loose)-heterochromatin (compact) ratio. (author)

Octopamine regulates antennal sensory neurons via daytime-dependent changes in cAMP and IP3 levels in the hawkmoth Manduca sexta.

Directory of Open Access Journals (Sweden)

Thomas Schendzielorz

Full Text Available The biogenic amine octopamine (OA mediates reward signals in olfactory learning and memory as well as circadian rhythms of sleep and activity. In the crepuscular hawkmoth Manduca sexta, OA changed pheromone detection thresholds daytime-dependently, suggesting that OA confers circadian control of olfactory transduction. Thus, with enzyme-linked immunosorbent assays we searched hawkmoth antennae for daytime-dependent changes in the concentration of OA and its respective second messengers. Antennal stimulation with OA raised cAMP- and IP3 levels. Furthermore, antennae expressed daytime-dependent changes in the concentration of OA, with maxima at Zeitgebertime (ZT 20 when moths were active and also maximal concentrations of cAMP occurred. Maximal IP3 levels at ZT 18 and 23 correlated with maximal flight activity of male moths, while minimal IP3 levels at dusk correlated with peaks of feeding activity. Half maximal effective concentration (EC50 for activation of the OA-receptor decreased during the moth's activity phase suggesting daytime-dependent changes in OA receptor sensitivity. With an antiserum against tyramine, the precursor of OA, two centrifugal neurons were detected projecting out into the sensory cell layer of the antenna, possibly mediating more rapid stimulus-dependent OA actions. Indeed, in fast kinetic assays OA receptor stimulation increased cAMP concentrations within 50 msec. Thus, we hypothesize that fast, stimulus-dependent centrifugal control of OA-release in the antenna occurs. Additional slow systemic OA actions might be based upon circadian release of OA into the hemolymph mediating circadian rhythms of antennal second messenger levels. The resulting rhythms of odor sensitivity are suggested to underlie circadian rhythms in odor-mediated behavior.

Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

Science.gov (United States)

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

2016-03-01

Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Nuclear data for advanced fast reactors

International Nuclear Information System (INIS)

Rabotnov, N.S.

2001-01-01

Interest revives to fast reactors as the only proven technology obviously able of satisfying human energy needs for the next millennium by using full energy content of both natural uranium resources and of vast stocks of depleted uranium. This interest stimulates revision and improvement of fast reactor ND. Progress in reactor calculations accuracy due to better codes and much faster computers also increases relative importance of the input data uncertainties, especially in case of small reactivity margin and fuels of equilibrium compositions. The main objects of corresponding R and D efforts should be minor actinides and heavy liquid metal coolant. Data error bands and covariance information also gain importance as necessary components of neutron physics calculations. (author)

The fast ratio: A rapid measure for testing the dominance of the fast component in the initial OSL signal from quartz

International Nuclear Information System (INIS)

Durcan, Julie A.; Duller, Geoff A.T.

2011-01-01

The signal from the fast component is usually considered preferable for quartz optically stimulated luminescence (OSL) dating, however its presence in a continuous wave (CW) OSL signal is often assumed, rather than verified. This paper presents an objective measure (termed the fast ratio) for testing the dominance of the fast component in the initial part of a quartz OSL signal. The ratio is based upon the photo ionisation cross-sections of the fast and medium components and the power of the measurement equipment used to record the OSL signal, and it compares parts of the OSL signal selected to represent the fast and medium components. The ability of the fast ratio to distinguish between samples whose CW-OSL signal is dominated by the fast and non-fast components is demonstrated by comparing the fast ratio with the contribution of the fast component calculated from curve deconvolution of measured OSL signals and from simulated data. The ratio offers a rapid method for screening a large number of OSL signals obtained for individual equivalent dose estimates, it can be calculated and applied as easily as other routine screening methods, and is transferrable between different aliquots, samples and measurement equipment. - Highlights: → Fast ratio is a measure which tests dominance of fast component in quartz OSL signals. → A fast ratio above 20 implies a CW-OSL signal is dominated by fast component. → Fast ratio can be easily and rapidly applied to a large number of OSL signals. → Uses include signal comparison, data screening, identify need for further analysis.

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

Science.gov (United States)

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

Effect of combined platinum and electron on the temperature dependence of forward voltage in fast recovery diode

International Nuclear Information System (INIS)

Jia Yun-Peng; Zhao Bao; Wu Yu; Zhou Xuan; Li Zhe; Tan Jian; Yang Fei

2015-01-01

The temperature dependences of forward voltage drop (V F ) of the fast recovery diodes (FRDs) are remarkably influenced by different lifetime controlled treatments. In this paper the results of an experimental study are presented, which are the lifetime controls of platinum treatment, electron irradiation treatment, and the combined treatment of the above ones. Based on deep level transient spectroscopy (DLTS) measurements, a new level E6 (E C -0.376 eV) is found in the combined lifetime treated (CLT) sample, which is different from the levels of the individual platinum and electron irradiation ones. Comparing the tested V F results of CLT samples with the others, the level E6 is responsible for the degradation of temperature dependence of the forward voltage drop in the FRD. (paper)

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

Science.gov (United States)

Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

DEFF Research Database (Denmark)

Alvarez Herrero, Susana; Calin, A; Graffmo, K S

2013-01-01

-onset, fast-progression SOD1(G127X) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle......-concentrations. It is possible that in SOD1(G127X) there is inadequate energy-dependent Na(+)/K(+) pumping, which may lead to a lethal Na(+) overload....

2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter

Directory of Open Access Journals (Sweden)

Zhentao Yang

2017-05-01

Full Text Available 2-hydroxyglutarate-(2-HG-mediated inhibition of TET2 activity influences DNA hypermethylation in cells harboring mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2. Here, we show that 2-HG also regulates DNA methylation mediated by DNA methyltransferase 1 (DNMT1. DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs and 2-HG-treated wild-type (WT MEFs. We found that 2-HG bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. In human glioma samples, RIP3 protein levels correlated negatively with IDH1 R132H levels. Furthermore, ectopic expression of RIP3 in transformed IDH1-mutated MEFs inhibited the growth of tumors derived from these cells following transplantation into nude mice. Thus, our research sheds light on a mechanism of 2-HG-induced DNA hypermethylation and suggests that impaired necroptosis contributes to the tumorigenesis driven by IDH1/2 mutations.

Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

Science.gov (United States)

Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

2016-01-01

Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

Energy Technology Data Exchange (ETDEWEB)

Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Gonchar, Ilya V., E-mail: ample@mail.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kharchenko, Marianna V., E-mail: mariannakharchenko@gmail.com [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kornilova, Elena S., E-mail: lenkor@mail.cytspb.rssi.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya, St.Petersburg, 195251 (Russian Federation)

2016-04-22

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

International Nuclear Information System (INIS)

Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

2016-01-01

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Preliminary framework for Familiar Auditory Sensory Training (FAST) provided during coma recovery.

Science.gov (United States)

Pape, Theresa Louise-Bender; Rosenow, Joshua M; Harton, Brett; Patil, Vijaya; Guernon, Ann; Parrish, Todd; Froehlich, Kathleen; Burress, Catherine; McNamee, Shane; Herrold, Amy A; Weiss, Bessie; Wang, Xue

2012-01-01

Since there remains a need to examine the nature of the neural effect and therapeutic efficacy/effectiveness of sensory stimulation provided to persons in states of seriously impaired consciousness, a passive sensory stimulation intervention, referred to as the Familiar Auditory Sensory Training (FAST) protocol, was developed for examination in an ongoing, double-blind, randomized clinical trial (RCT). The FAST protocol is described in this article according to the preliminary framework, which is a synthesis of knowledge regarding principles of plasticity and capabilities of the human brain to automatically and covertly process sensory input. Feasibility issues considered during the development of the intervention are also described. To enable replication of this intervention, we describe procedures to create the intervention and lessons learned regarding the creation process. The potential effect of the intervention is illustrated using functional brain imaging of nondisabled subjects. This illustration also demonstrates the relevance of the rationale for designing the FAST protocol. To put the intervention within the context of the scientific development process, the article culminates with a description of the study design for the ongoing RCT examining the efficacy of the FAST protocol.

Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

Science.gov (United States)

Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

2017-06-01

Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline

Fast neutron dosimetry. Progress report, July 1, 1979-June 30, 1980

International Nuclear Information System (INIS)

Attix, F.H.

1980-01-01

Progress is reported in: the development and testing of new gas mixtures more suitable for fast neutron dosimetry using the common A150-type Tissue-equivalent plastic ion chambers; comparison of photon doses determined with a graphite-walled proportional counter and with paired dosimeters irradiated by 14.8-MeV neutrons; a detector for the direct measurement of LET distributions from irradiation with fast neutrons; LET distributions from fast neutron irradiation of TE-plastic and graphite measured in a cylindrically symmetric geometry; progress in development of a tandem fast neutron and 60 Co gamma ray source irradiation facility; an approach to the correlation of cellular response with lineal energy; calculated and measured HTO atmospheric dispersion rates within meters of a release site; application of cavity theory to fast neutrons; and fast neutron dosimetry by thermally stimulated currents in Al 2 O 3

TGF beta-1 dependent fast stimulation of ATM and p53 phosphorylation following exposure to ionizing radiation does not involve TGF beta-receptor I signalling

NARCIS (Netherlands)

Wiegman, Erwin M.; Blaese, Marcet A.; Loeffler, Heidi; Coppes, Rob P.; Rodemann, H. Peter

Background and purpose: It has been proposed that radiation induced stimulation of ATM and downstream components involves activation of TGF beta-1 and that this may be due to TGF beta-1-receptor I-Smad signalling. Therefore, the aim of this study was to clarify the distinct role of TGF

Optical annealing of CaF2:Mn for cooled optically stimulated luminescence

International Nuclear Information System (INIS)

Miller, S.D.; Stahl, K.A.; Endres, G.W.R.; McDonald, J.C.

1989-01-01

Optical annealing of the cooled optically stimulated luminescence in CaF 2 :Mn at room temperature has been demonstrated. The laser of choice for optical annealing of CaF 2 : Mn is a 326 nm helium-cadmium ultraviolet laser. A complete cycle of readout and annealing of the CaF 2 :Mn cooled optically stimulated dosemeters can now be accomplished without heating the dosemeters above room temperature. This annealing work represents the next step toward creating a proton-recoil-based fast neutron dosimetry system based on the cooled optically stimulated luminescence technique. (author)

Physiological adaptations to fasting in an actively wintering canid, the Arctic blue fox (Alopex lagopus).

Science.gov (United States)

Mustonen, Anne-Mari; Pyykönen, Teija; Puukka, Matti; Asikainen, Juha; Hänninen, Sari; Mononen, Jaakko; Nieminen, Petteri

2006-01-01

This study investigated the physiological adaptations to fasting using the farmed blue fox (Alopex lagopus) as a model for the endangered wild arctic fox. Sixteen blue foxes were fed throughout the winter and 32 blue foxes were fasted for 22 d in Nov-Dec 2002. Half of the fasted blue foxes were food-deprived again for 22 d in Jan-Feb 2003. The farmed blue fox lost weight at a slower rate (0.97-1.02% body mass d(-1)) than observed previously in the arctic fox, possibly due to its higher initial body fat content. The animals experienced occasional fasting-induced hypoglycaemia, but their locomotor activity was not affected. The plasma triacylglycerol and glycerol concentrations were elevated during phase II of fasting indicating stimulated lipolysis, probably induced by the high growth hormone concentrations. The total cholesterol, HDL- and LDL-cholesterol, urea, uric acid and total protein levels and the urea:creatinine ratio decreased during fasting. Although the plasma levels of some essential amino acids increased, the blue foxes did not enter phase III of starvation characterized by stimulated proteolysis during either of the 22-d fasting procedures. Instead of excessive protein catabolism, it is liver dysfunction, indicated by the increased plasma bilirubin levels and alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase activities, that may limit the duration of fasting in the species.

Stimulation of phagocytosis by sulforaphane

International Nuclear Information System (INIS)

Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

2011-01-01

Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2 -/- mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

Stimulation of phagocytosis by sulforaphane

Energy Technology Data Exchange (ETDEWEB)

Suganuma, Hiroyuki, E-mail: hsuganu1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Fahey, Jed W., E-mail: jfahey@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Bryan, Kelley E., E-mail: kbryanm1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Healy, Zachary R., E-mail: zhealy1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Talalay, Paul, E-mail: ptalalay@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States)

2011-02-04

Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

Determination of spatially dependent transfer function of zero power reactor by using pseudo-random incentive

International Nuclear Information System (INIS)

Kostic, Lj.

1973-01-01

Specially constructed fast reactivity oscillator was stimulating the zero power reactor by a stimulus which caused pseudo-random reactivity changes. Measuring system included stochastic oscillator BCR-1 supplied by pseudo-random pulses from noise generator GBS-16, instrumental tape-recorder, system for data acquisition and digital computer ZUSE-Z-23. For measuring the spatially dependent transfer function, reactor response was measured at a number of different positions of stochastic oscillator and ionization chamber. In order to keep the reactor system linear, experiment was limited to small reactivity fluctuations. Experimental results were compared to theoretical ones

Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase.

Science.gov (United States)

Hussain, Zahir; Uyama, Toru; Kawai, Katsuhisa; Binte Mustafiz, Smriti Sultana; Tsuboi, Kazuhito; Araki, Nobukazu; Ueda, Natsuo

2018-05-01

N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca 2+ -dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A 2 (cPLA 2 ε) was recently identified as a Ca 2+ -dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA 2 ε function as Ca-NAT. We next purified both mouse recombinant cPLA 2 ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca 2+ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1 mM CaCl 2 and lowered the EC 50 value of Ca 2+ >8-fold. Using a PS probe, we showed that cPLA 2 ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA 2 ε with PS in living cells. Finally, we found that the Ca 2+ -ionophore ionomycin increased [ 14 C]NAPE levels >10-fold in [ 14 C]ethanolamine-labeled cPLA 2 ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca 2+ -independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca 2+ -dependent activity and human cPLA 2 ε isoforms also functioned as Ca-NAT. Copyright © 2018 Elsevier B.V. All rights reserved.

Neomysin inhibits Ca2+-stimulated phosphatidylinositol hydrolysis and protects cultured rat cardiomyocytes from Ca2+-dependent cell injury

International Nuclear Information System (INIS)

Babson, J.R.; Dougherty, J.M.

1991-01-01

Exposure of cultured rat cardiomyocytes to ionomycin and extracellular Ca 2+ leads to a rapid, sustained increase in intracellular free Ca 2+ as monitored by Ca 2+ -dependent phosphorylase a activation and to a subsequent loss of cardiomyocyte viability as determined by lactate dehydrogenase (LDH) leakage. The intracellular free Ca 2+ increase coincided with a rapid hydrolysis of phosphatidylinositol that preceded cell death. Phosphatidylinositol hydrolysis was monitored by the release of radiolabeled phosphoinositides from cardiomyocytes prelabeled with [2- 3 H]-myo-inositol. Neomycin, a known inhibitor of phospholipase C, inhibited the phosphatidylinositol hydrolysis and markedly reduced the extent of cell injury. Inhibitors of other Ca 2+ -activated processes, including intracellular proteases and phospholipase A 2 , had no effect on ionomycin-mediated cell injury. These data suggest that ionomycin-induced Ca 2+ -dependent cell injury in cultured cardiomyocytes may be due in part to the stimulation of phosphatidylinositol hydrolysis, presumably catalyzed by a Ca 2+ -dependent phospholipase C

Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

International Nuclear Information System (INIS)

Hepler, J.R.; Harden, T.K.

1986-01-01

Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells

Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles.

Science.gov (United States)

Clausen, T; Overgaard, K; Nielsen, O B

2004-02-01

Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles. Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded. During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus. The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.

Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

Directory of Open Access Journals (Sweden)

Tania J Fernandes

Full Text Available In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and β-glycerophosphate these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM, and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2 actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells

Effects of polycationic compounds on mitogen stimulation

DEFF Research Database (Denmark)

Heron, I; Larsen, B; Hokland, M

1981-01-01

The effects of polycations added to phytomitogen stimulated human lymphocyte cultures have been studied. Within certain dose ranges all polycations tested gave rise to augmented thymidine uptake in mitogen stimulated cultures. The optimum enhancing concentrations of polycations was depending on t...

Particle trapping in stimulated scattering processes

International Nuclear Information System (INIS)

Karttunen, S.J.; Heikkinen, J.A.

1981-01-01

Particle trapping effects on stimulated Brillouin and Raman scattering are investigated. A time and space dependent model assumes a Maxwellian plasma which is taken to be homogeneous in the interaction region. Ion trapping has a rather weak effect on stimulated Brillouin scattering and large reflectivities are obtained even in strong trapping regime. Stimulated Raman scattering is considerably reduced by electron trapping. Typically 15-20 times larger laser intensities are required to obtain same reflectivity levels than without trapping. (author)

A fast and accurate method for perturbative resummation of transverse momentum-dependent observables

Science.gov (United States)

Kang, Daekyoung; Lee, Christopher; Vaidya, Varun

2018-04-01

We propose a novel strategy for the perturbative resummation of transverse momentum-dependent (TMD) observables, using the q T spectra of gauge bosons ( γ ∗, Higgs) in pp collisions in the regime of low (but perturbative) transverse momentum q T as a specific example. First we introduce a scheme to choose the factorization scale for virtuality in momentum space instead of in impact parameter space, allowing us to avoid integrating over (or cutting off) a Landau pole in the inverse Fourier transform of the latter to the former. The factorization scale for rapidity is still chosen as a function of impact parameter b, but in such a way designed to obtain a Gaussian form (in ln b) for the exponentiated rapidity evolution kernel, guaranteeing convergence of the b integral. We then apply this scheme to obtain the q T spectra for Drell-Yan and Higgs production at NNLL accuracy. In addition, using this scheme we are able to obtain a fast semi-analytic formula for the perturbative resummed cross sections in momentum space: analytic in its dependence on all physical variables at each order of logarithmic accuracy, up to a numerical expansion for the pure mathematical Bessel function in the inverse Fourier transform that needs to be performed just once for all observables and kinematics, to any desired accuracy.

Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.

Science.gov (United States)

Labedi, Adnan; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

2014-01-01

Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition. Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors. In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects. Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. Copyright © 2014 Elsevier Inc. All rights reserved.

Fast neutron dosimetry. Progress report, July 1, 1979-June 30, 1980

Energy Technology Data Exchange (ETDEWEB)

Attix, F.H.

1980-01-01

Progress is reported in: the development and testing of new gas mixtures more suitable for fast neutron dosimetry using the common A150-type Tissue-equivalent plastic ion chambers; comparison of photon doses determined with a graphite-walled proportional counter and with paired dosimeters irradiated by 14.8-MeV neutrons; a detector for the direct measurement of LET distributions from irradiation with fast neutrons; LET distributions from fast neutron irradiation of TE-plastic and graphite measured in a cylindrically symmetric geometry; progress in development of a tandem fast neutron and /sup 60/Co gamma ray source irradiation facility; an approach to the correlation of cellular response with lineal energy; calculated and measured HTO atmospheric dispersion rates within meters of a release site; application of cavity theory to fast neutrons; and fast neutron dosimetry by thermally stimulated currents in Al/sub 2/O/sub 3/. (GHT)

Novel applications of fast neutron interrogation methods

International Nuclear Information System (INIS)

Gozani, Tsahi

1994-01-01

The development of non-intrusive inspection methods for contraband consisting primarily of carbon, nitrogen, oxygen, and hydrogen requires the use of fast neutrons. While most elements can be sufficiently well detected by the thermal neutron capture process, some important ones, e.g., carbon and in particular oxygen, cannot be detected by this process. Fortunately, fast neutrons, with energies above the threshold for inelastic scattering, stimulate relatively strong and specific gamma ray lines from these elements. The main lines are: 6.13 for O, 4.43 for C, and 5.11, 2.31 and 1.64 MeV for N. Accelerator-generated neutrons in the energy range of 7 to 15 MeV are being considered as interrogating radiations in a variety of non-intrusive inspection systems for contraband, from explosives to drugs and from coal to smuggled, dutiable goods. In some applications, mostly for inspection of small items such as luggage, the decision process involves a rudimentary imaging, akin to emission tomography, to obtain the localized concentration of various elements. This technique is called FNA - Fast Neutron Analysis. While this approach offers improvements over the TNA (Thermal Neutron Analysis), it is not applicable to large objects such as shipping containers and trucks. For these challenging applications, a collimated beam of neutrons is rastered along the height of the moving object. In addition, the neutrons are generated in very narrow nanosecond pulses. The point of their interaction inside the object is determined by the time of flight (TOF) method, that is measuring the time elapsed from the neutron generation to the time of detection of the stimulated gamma rays. This technique, called PFNA (Pulsed Fast Neutron Analysis), thus directly provides the elemental, and by inference, the chemical composition of the material at every volume element (voxel) of the object. The various neutron-based techniques are briefly described below. ((orig.))

Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells

International Nuclear Information System (INIS)

Chung, Byung-Hee; Kim, Jong-Dai; Kim, Chun-Ki; Kim, Jung Huan; Won, Moo-Ho; Lee, Han-Soo; Dong, Mi-Sook; Ha, Kwon-Soo; Kwon, Young-Geun; Kim, Young-Myeong

2008-01-01

We investigated the molecular effect and signal pathway of icariin, a major flavonoid of Epimedium koreanum Nakai, on angiogenesis. Icariin stimulated in vitro endothelial cell proliferation, migration, and tubulogenesis, which are typical phenomena of angiogenesis, as well as increased in vivo angiogenesis. Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis. Icariin-induced ERK activation and angiogenic events were significantly inhibited by the MEK inhibitor PD98059, without affecting Akt and eNOS phosphorylation. The PI3K inhibitor Wortmannin suppressed icariin-mediated angiogenesis and Akt and eNOS activation without affecting ERK phosphorylation. Moreover, the NOS inhibitor NMA partially reduced the angiogenic activity of icariin. These results suggest that icariin stimulated angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways and may be a useful drug for angiogenic therapy

The Effect of Cerebellar Transcranial Direct Current Stimulation on A Throwing Task Depends on Individual Level of Task Performance.

Science.gov (United States)

Mizuguchi, Nobuaki; Katayama, Takashi; Kanosue, Kazuyuki

2018-02-10

The effect of cerebellar transcranial direct current stimulation (tDCS) on motor performance remains controversial. Some studies suggest that the effect of tDCS depends upon task-difficulty and individual level of task performance. Here, we investigated whether the effect of cerebellar tDCS on the motor performance depends upon the individual's level of performance. Twenty-four naïve participants practiced dart throwing while receiving a 2-mA cerebellar tDCS for 20 min under three stimulus conditions (anodal-, cathodal-, and sham-tDCS) on separate days with a double-blind, counter-balanced cross-over design. Task performance was assessed by measuring the distance between the center of the bull's eye and the dart's position. Although task performance tended to improve throughout the practice under all stimulus conditions, improvement within a given day was not significant as compared to the first no-stimulus block. In addition, improvement did not differ among stimulation conditions. However, the magnitude of improvement was associated with an individual's level of task performance only under cathodal tDCS condition (p performance improvement only for the sub-group of participants with lower performance levels as compared to that with sham-tDCS (p task performance. Thus, cerebellar tDCS would facilitate learning of a complex motor skill task only in a subset of individuals. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes.

Science.gov (United States)

Pabbidi, M R; Ji, X; Maxwell, J T; Mignery, G A; Samarel, A M; Lipsius, S L

2016-01-01

We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in-PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in-PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In-PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in-PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of �

Ab initio simulation of stimulated bremsstrahlung in an intense laser field

International Nuclear Information System (INIS)

Volkova, E.A.; Popov, A.M.; Popovicheva, O.B.

1992-01-01

Numerical solution of the time-dependent Schroedinger equation for a quantum system in the field of an electromagnetic wave is used to study a one-dimensional model of stimulated bremsstrahlung (absorption or emission of photons by a field in connection with Coulomb scattering of an electron). The time dependence of the stimulated bremsstrahlung effect is analyzed for various laser radiation intensities. The process of stimulated photorecombination is examined. The results of the calculation are compared with the analytical theory of the stimulated bremsstrahlung effect. 14 refs., 6 figs

Fast-scan cyclic voltammetry (FSCV) detection of endogenous octopamine in Drosophila melanogaster ventral nerve cord

Science.gov (United States)

Pyakurel, Poojan; Privman, Eve; Venton, B. Jill

2016-01-01

Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. An FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval VNC. Repeated stimulations were stable with 2 or 5 minutes interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain. PMID:27326831

Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

Science.gov (United States)

Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

2012-01-01

Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

Rapid Categorization of Human and Ape Faces in 9-Month-Old Infants Revealed by Fast Periodic Visual Stimulation.

Science.gov (United States)

Peykarjou, Stefanie; Hoehl, Stefanie; Pauen, Sabina; Rossion, Bruno

2017-10-02

This study investigates categorization of human and ape faces in 9-month-olds using a Fast Periodic Visual Stimulation (FPVS) paradigm while measuring EEG. Categorization responses are elicited only if infants discriminate between different categories and generalize across exemplars within each category. In study 1, human or ape faces were presented as standard and deviant stimuli in upright and inverted trials. Upright ape faces presented among humans elicited strong categorization responses, whereas responses for upright human faces and for inverted ape faces were smaller. Deviant inverted human faces did not elicit categorization. Data were best explained by a model with main effects of species and orientation. However, variance of low-level image characteristics was higher for the ape than the human category. Variance was matched to replicate this finding in an independent sample (study 2). Both human and ape faces elicited categorization in upright and inverted conditions, but upright ape faces elicited the strongest responses. Again, data were best explained by a model of two main effects. These experiments demonstrate that 9-month-olds rapidly categorize faces, and unfamiliar faces presented among human faces elicit increased categorization responses. This likely reflects habituation for the familiar standard category, and stronger release for the unfamiliar category deviants.

A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange

DEFF Research Database (Denmark)

Liu, Yi; Dentin, Renaud; Chen, Danica

2008-01-01

During early fasting, increases in skeletal muscle proteolysis liberate free amino acids for hepatic gluconeogenesis in response to pancreatic glucagon. Hepatic glucose output diminishes during the late protein-sparing phase of fasting, when ketone body production by the liver supplies compensatory...... expression through the dephosphorylation and nuclear shuttling of forkhead box O1 (FOXO1). Here we show that a fasting-inducible switch, consisting of the histone acetyltransferase p300 and the nutrient-sensing deacetylase sirtuin 1 (SIRT1), maintains energy balance in mice through the sequential induction...... of CRTC2 and FOXO1. After glucagon induction, CRTC2 stimulated gluconeogenic gene expression by an association with p300, which we show here is also activated by dephosphorylation at Ser 89 during fasting. In turn, p300 increased hepatic CRTC2 activity by acetylating it at Lys 628, a site that also...

RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

Energy Technology Data Exchange (ETDEWEB)

Hahm, Jong Ryeal [Department of Internal Medicine, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Ahmed, Mahmoud [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of)

2016-09-09

3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-L-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-L-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity. - Highlights: • Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. • SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. • RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. • RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. • RKIP-dependent ERK1 activation increases triacylglycerides in

Thermically stimulated exoelectronic emissions and thermoluminescence of MgO

International Nuclear Information System (INIS)

Chubaci, J.F.D.

1987-01-01

In this work, studies were performed on the following topics: i) thermically stimulated exoelectronic emission (TSEE) in pure MgO single crystals ion implanted, submitted to thermal treatment with fast on slow cooling and water adsorption; ii) ultraviolet light effect on TSEE; iii) thermoluminescent emission; iv) crystallization of FeCoB amorphous alloys. (A.C.A.S.) [pt

Myomaker mediates fusion of fast myocytes in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Landemaine, Aurélie; Rescan, Pierre-Yves; Gabillard, Jean-Charles, E-mail: Jean-charles.gabillard@rennes.inra.fr

2014-09-05

Highlights: • Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. • Myomaker is essential for fast myocyte fusion in zebrafish. • The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi.

A Fast EEG Forecasting Algorithm for Phase-Locked Transcranial Electrical Stimulation of the Human Brain

Directory of Open Access Journals (Sweden)

Farrokh Mansouri

2017-07-01

Full Text Available A growing body of research suggests that non-invasive electrical brain stimulation can more effectively modulate neural activity when phase-locked to the underlying brain rhythms. Transcranial alternating current stimulation (tACS can potentially stimulate the brain in-phase to its natural oscillations as recorded by electroencephalography (EEG, but matching these oscillations is a challenging problem due to the complex and time-varying nature of the EEG signals. Here we address this challenge by developing and testing a novel approach intended to deliver tACS phase-locked to the activity of the underlying brain region in real-time. This novel approach extracts phase and frequency from a segment of EEG, then forecasts the signal to control the stimulation. A careful tuning of the EEG segment length and prediction horizon is required and has been investigated here for different EEG frequency bands. The algorithm was tested on EEG data from 5 healthy volunteers. Algorithm performance was quantified in terms of phase-locking values across a variety of EEG frequency bands. Phase-locking performance was found to be consistent across individuals and recording locations. With current parameters, the algorithm performs best when tracking oscillations in the alpha band (8–13 Hz, with a phase-locking value of 0.77 ± 0.08. Performance was maximized when the frequency band of interest had a dominant frequency that was stable over time. The algorithm performs faster, and provides better phase-locked stimulation, compared to other recently published algorithms devised for this purpose. The algorithm is suitable for use in future studies of phase-locked tACS in preclinical and clinical applications.

Representation of the body in the lateral striatum of the freely moving rat: Fast Spiking Interneurons respond to stimulation of individual body parts.

Science.gov (United States)

Kulik, Julianna M; Pawlak, Anthony P; Kalkat, Manraj; Coffey, Kevin R; West, Mark O

2017-02-15

Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input

Formation of double-strand breaks in DNA of γ-irradiated bacteria depending on the function of fast repair processes of DNA single-strand breaks

International Nuclear Information System (INIS)

Petrov, S.I.; Gaziev, A.I.

1980-01-01

The formation of double-strand breaks in DNA of γ-irradiated ( 60 Co)Ex coli bacteria depending on the function of fast repair processes of DNA single-strand breaks, is investigated. The profiles of sedimentation of DNA Ex coli cells, irradiated at 0-2 deg C in the salt medium and in EDTA-borate buffer, are presented. It is shown that when irradiating cells in EDTA-borate buffer, the output of single- and double strand breaks in DNA is much higher than in the case of their irradiation in the minimum salt medium. The dependence of output of single-strand and double-strand breaks depending on the radiatier doze of E coli cells in the salt medium and EDTA-borate buffer, is studied. The supposition is made on the presence of a regulative interaction between the accumulation of DNA single-breaks and their repair with the formation of double-strand breaks. The functionating of fast and superfast repair processes considerably affects the formation of double-strand breaks in DNA of a bacterium cell. A considerable amount of double-breaks registered immediately after irradiation forms due to a close position of single-strand breaks on the opposite DNA strands

Dependences of the geometrical parameters of cell community on stimulation voltage and frequency in chick embryonic cardiomyocytes

Science.gov (United States)

Fujii, Koki; Nomura, Fumimasa; Kaneko, Tomoyuki

2018-03-01

To investigate the optimal conditions for electrical stimulation, communities of lined-up chick embryonic cardiomyocytes were evaluated in terms of their threshold voltage for pacing (PVMin) and the half-maximum paced frequency (PF50), with a focus on the following factors: (1) the orientation of the major axis of cell communities to the electric field (EF) direction as the external factor; (2) the number of cells in a cell community, the length of the cell community, and the mean length of cells comprising the community as the internal factors. Firstly, PVMin decreased with increasing length of the cell network oriented parallel to the EF. PVMin was approximately 0.041 ± 0.025 V/mm when the community was sufficiently long. On the other hand, PVMin in the orthogonal orientation was constant at 1.7 ± 0.047 V/mm with no dependence on the length of the cell network. Secondly, we found that PF50 increased with increasing length of the cell network or the number of cells in the network; the PF50 values were 2.03 ± 0.05 and 3.39 ± 0.05 Hz when the respective cell network lengths were 100 µm (n = 43) and more than 300 µm (n = 6) and the cells were oriented parallel to the EF. These findings indicate that it is important to suppress ventricular fibrillation with minimal efficient stimulation by considering the EF direction with respect to the orientation of cardiomyocytes. Furthermore, expanded cells showed the loss of ability to respond to stimulation at higher frequencies. Cardiomyocytes combined with seeded fibroblasts as a cell network at a low density are a possible model of a ventricular remodeling heart.

Functional Assessment of Corticospinal Conduction with Transcranial Magnetic Stimulation: Basic Principles

DEFF Research Database (Denmark)

Groppa, S.; Peller, M.; Siebner, Hartwig R.

2010-01-01

Here we review how transcranial magnetic stimulation (TMS) is used in clinical practice to examine the functional integrity of the fast conducting fibres of the human corticomotor path ways. We first summarise the technical and physiological principles of TMS that are relevant to its clinical use...

Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening

Directory of Open Access Journals (Sweden)

Silvia ePicazio

2015-03-01

Full Text Available Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT. The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect. Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.

Rationale for Using Exercise in the Treatment of Stimulant Use Disorders

Science.gov (United States)

Greer, Tracy L.; Ring, Kolette M.; Warden, Diane; Grannemann, Bruce D.; Church, Timothy S.; Somoza, Eugene; Blair, Steven N.; Szapocznik, Jose; Stoutenberg, Mark; Rethorst, Chad; Walker, Robrina; Morris, David W.; Kosinski, Andrzej S.; Kyle, Tiffany; Marcus, Bess; Crowell, Becca; Oden, Neal; Nunes, Edward; Trivedi, Madhukar H.

2013-01-01

Novel approaches to the treatment of stimulant abuse and dependence are needed. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse. In addition, exercise has been associated with improvements in many other health-related areas that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight, quality of life, and anhedonia. Neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes in stimulant abuse. The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. If effective, exercise may provide an additional approach to the treatment of stimulant use disorders. PMID:25364477

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

Science.gov (United States)

Licata, Stephanie C; Lowen, Steven B; Trksak, George H; Maclean, Robert R; Lukas, Scott E

2011-08-15

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. Copyright © 2011 Elsevier Inc. All rights reserved.

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

Science.gov (United States)

Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2011-01-01

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

Perceived Intensity and Discrimination Ability for Lingual Electrotactile Stimulation Depends on Location and Orientation of Electrodes

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Leslie M. Stone-Roy

2017-04-01

Full Text Available Malfunctioning sensory systems can severely impact quality of life and repair is not always possible. One solution, called sensory substitution, is to use another sensory system to bring lost information to the brain. This approach often involves the use of bioengineered devices that electrically stimulate somatosensory fibers. Interestingly, the tongue is an ideal location for electrotactile stimulation due to its dense innervation, moisture, and protected environment. Success with transmitting visual and vestibular information through the tongue indicates promise for future applications. However, sensitivity and discrimination ability varies between individuals and across the tongue surface complicating efforts to produce reliable and consistent sensations. The goals of the present study were to investigate these differences more precisely to better understand the mechanosensory innervation of the tongue so that future electrotactile devices can be designed more effectively. Specifically, we tested whether stimulation of certain regions of the tongue consistently result in better perception, whether the spacing of stimulating electrodes affects perceived intensity, and whether the orientation of electrodes affects perceived intensity and discrimination. To test these hypotheses, we built a custom tongue stimulation device, recruited 25 participants, and collected perceived intensity and discrimination data. We then subjected the data to thorough statistical analyses. Consistent with previous studies, we found that stimulation of the anterior medial tongue region was perceived as more intense than stimulation of lateral and posterior regions. This region also had the best discrimination ability for electrodes. Dividing the stimulated tongue area into 16 distinct regions allowed us to compare perception ability between anterior and posterior regions, medial and lateral regions, and the left and right sides of the tongue. Stimulation of the most

An interferometer experiment to explore the aspect angle dependence of stimulated electromagnetic emission spectra

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Isham

2005-01-01

Full Text Available When the Earth's ionosphere is irradiated by a radiofrequency (RF electromagnetic wave of sufficiently high power density and tuned to match a natural E- or F-region plasma frequency, ionospheric magnetoionic wave modes may be excited and may generate RF electromagnetic sideband waves via nonlinear interactions. These secondary emissions, which may then escape from the ionosphere, have been termed stimulated electromagnetic emission or SEE. The frequency spectra of this radiation has been studied extensively, and a number of characteristic spectral features have been identified and in some cases related to particular plasma processes. The separation in frequency between the RF pump and the harmonics of the local electron gyrofrequency is critical in determining the amount of anomalous absorption suffered by the pump wave and the spectral properties of the stimulated sidebands. The pump can excite electrostatic waves which do not propagate away but can in some cases be observed via radio-wave scattering from the electron density fluctuations associated with them. These enhanced density fluctuations are created by processes commonly referred to as upper-hybrid and Langmuir turbulence. Langmuir turbulence has been the subject of 930-MHz scattering observations with antenna scanning through several pre-selected angles between the geographic and geomagnetic zenith directions, and a preference for pointing angles between the Spitze angle and geomagnetic field-aligned was identified. Other phenomena, such as the generation of enhanced electron temperatures and artificial aurora, have more recently been shown to have special behavior at similar angles, near but apparently not quite at field-aligned. In view of this evidence for angular structure in several pump-induced effects, in light of the rich variety of SEE phenomena strongly dependent on the geomagnetic field via the frequency interval between the pump and the gyrofrequency harmonics, and in

An interferometer experiment to explore the aspect angle dependence of stimulated electromagnetic emission spectra

Directory of Open Access Journals (Sweden)

Isham

2005-01-01

Full Text Available When the Earth's ionosphere is irradiated by a radiofrequency (RF electromagnetic wave of sufficiently high power density and tuned to match a natural E- or F-region plasma frequency, ionospheric magnetoionic wave modes may be excited and may generate RF electromagnetic sideband waves via nonlinear interactions. These secondary emissions, which may then escape from the ionosphere, have been termed stimulated electromagnetic emission or SEE. The frequency spectra of this radiation has been studied extensively, and a number of characteristic spectral features have been identified and in some cases related to particular plasma processes. The separation in frequency between the RF pump and the harmonics of the local electron gyrofrequency is critical in determining the amount of anomalous absorption suffered by the pump wave and the spectral properties of the stimulated sidebands. The pump can excite electrostatic waves which do not propagate away but can in some cases be observed via radio-wave scattering from the electron density fluctuations associated with them. These enhanced density fluctuations are created by processes commonly referred to as upper-hybrid and Langmuir turbulence. Langmuir turbulence has been the subject of 930-MHz scattering observations with antenna scanning through several pre-selected angles between the geographic and geomagnetic zenith directions, and a preference for pointing angles between the Spitze angle and geomagnetic field-aligned was identified. Other phenomena, such as the generation of enhanced electron temperatures and artificial aurora, have more recently been shown to have special behavior at similar angles, near but apparently not quite at field-aligned. In view of this evidence for angular structure in several pump-induced effects, in light of the rich variety of SEE phenomena strongly dependent on the geomagnetic field via the frequency interval between the pump and the gyrofrequency harmonics, and in view

Nitric Oxide Synthase 1 Modulates Basal and β-Adrenergic-Stimulated Contractility by Rapid and Reversible Redox-Dependent S-Nitrosylation of the Heart

Science.gov (United States)

Vielma, Alejandra Z.; León, Luisa; Fernández, Ignacio C.; González, Daniel R.

2016-01-01

S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC. Selective NOS-1 blockade with S-methyl-L-thiocitrulline (SMTC) and Nω-propyl-l-arginine decreased basal contractility and relaxation (−25–30%) and basal S-nitrosylation of total proteins (−25–60%), RyR2, SERCA2 and LTCC (−60–75%). NOS-1 inhibition reduced (−25–40%) the inotropic response and protein S-nitrosylation induced by isoproterenol, particularly that of RyR2 (−85±7%). Tempol, a superoxide scavenger, mimicked the effects of NOS-1 inhibition on inotropism and protein S-nitrosylation; whereas selective NOS-3 inhibitor L-N5-(1-Iminoethyl)ornithine had no effect. Inhibition of NOS-1 did not affect phospholamban phosphorylation, but reduced its oligomerization. Attenuation of contractility was abolished by PKA blockade and unaffected by guanylate cyclase inhibition. Additionally, in isolated mouse cardiomyocytes, NOS-1 inhibition or removal reduced the Ca2+-transient amplitude and sarcomere shortening induced by isoproterenol or by direct PKA activation. We conclude that 1) normal cardiac performance requires basal NOS-1 activity and S-nitrosylation of the calcium-cycling machinery; 2) β-adrenergic stimulation induces rapid and reversible NOS-1 dependent, PKA and ROS-dependent, S-nitrosylation of RyR2 and other proteins, accounting for about one third of its

Cyclic AMP-dependent protein kinase interferes with GTP γS stimulated IP3 formation in differentiated HL-60 cell membranes

International Nuclear Information System (INIS)

Misaki, Naoyuki; Imaizumi, Taro; Watanabe, Yashuiro

1989-01-01

The effects of addition of activated cyclic AMP-dependent protein kinase (PKA) on the function of islet-activating protein (IAP)-sensitive GTP-binding (G) protein were studied in the plasma membranes of 3 H-inositol-labeled differentiated human leukemic (HL-60) cells. Pretreatment of the membranes with activated PKA in the presence of MgATP for 15 min. at 37 degree C decreased GTP γS-stimulated inositol trisphosphate (IP 3 ) formation by about 30%, but had no influence on Ca 2+ -stimulated IP 3 formation. And autoradiography in the phosphorylation experiments of solubilized HL-60 cell membranes by PKA showed some 32 P incorporated bands, and among them one of the major bands showed the migration at 40 kDa supporting that the G protein coupling with PI response was phosphorylated by PKA. These results showed that pretreatment with activated PKA inhibited the mediating function of the G protein between the fMLP receptor and phospholipase C by its phosphorylation

Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

Science.gov (United States)

Kirwan, John P.; Rote, Neal S.; Minium, Judi

2013-01-01

Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Plasma MMP9 and C-reactive protein (CRP) were measured from fasting blood samples. Truncal fat was determined by DEXA. Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls. Obese women with PCOS exhibited greater EGR-1 and TF protein content after glucose ingestion, and plasma CRP levels were even higher compared with lean subjects regardless of PCOS status. Truncal fat correlated with MMP9 and CRP levels and glucose-stimulated increases in AP-1 activation and EGR-1 and TF protein content. Testosterone correlated with glucose-stimulated AP-1 activation, and androstenedione correlated with MMP9 and CRP levels and glucose-stimulated AP-1 activation. Thus, both PCOS and obesity contribute to an atherothrombotic state in which excess abdominal adiposity and hyperandrogenism may be specific risk factors for developing atherothrombosis. PMID:23249695

Precise Aperture-Dependent Motion Compensation with Frequency Domain Fast Back-Projection Algorithm

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Man Zhang

2017-10-01

Full Text Available Precise azimuth-variant motion compensation (MOCO is an essential and difficult task for high-resolution synthetic aperture radar (SAR imagery. In conventional post-filtering approaches, residual azimuth-variant motion errors are generally compensated through a set of spatial post-filters, where the coarse-focused image is segmented into overlapped blocks concerning the azimuth-dependent residual errors. However, image domain post-filtering approaches, such as precise topography- and aperture-dependent motion compensation algorithm (PTA, have difficulty of robustness in declining, when strong motion errors are involved in the coarse-focused image. In this case, in order to capture the complete motion blurring function within each image block, both the block size and the overlapped part need necessary extension leading to degeneration of efficiency and robustness inevitably. Herein, a frequency domain fast back-projection algorithm (FDFBPA is introduced to deal with strong azimuth-variant motion errors. FDFBPA disposes of the azimuth-variant motion errors based on a precise azimuth spectrum expression in the azimuth wavenumber domain. First, a wavenumber domain sub-aperture processing strategy is introduced to accelerate computation. After that, the azimuth wavenumber spectrum is partitioned into a set of wavenumber blocks, and each block is formed into a sub-aperture coarse resolution image via the back-projection integral. Then, the sub-aperture images are straightforwardly fused together in azimuth wavenumber domain to obtain a full resolution image. Moreover, chirp-Z transform (CZT is also introduced to implement the sub-aperture back-projection integral, increasing the efficiency of the algorithm. By disusing the image domain post-filtering strategy, robustness of the proposed algorithm is improved. Both simulation and real-measured data experiments demonstrate the effectiveness and superiority of the proposal.

Effects of intermittent theta-burst stimulation on practice-related changes in fast finger movements in healthy subjects.

Science.gov (United States)

Agostino, Rocco; Iezzi, Ennio; Dinapoli, Loredana; Suppa, Antonio; Conte, Antonella; Berardelli, Alfredo

2008-08-01

In this paper we investigated the effects of intermittent theta-burst stimulation (iTBS) applied to the primary motor cortex on practice-related changes in motor performance. Seventeen healthy subjects underwent two experimental sessions, one testing real iTBS and the other testing sham iTBS. Before and after both iTBS sessions, the subjects practiced fast right index-finger abductions for a few minutes. As measures of cortical excitability we calculated resting motor threshold and motor-evoked potential amplitude. As measures of practice-related changes we evaluated the mean movement amplitude, peak velocity and peak acceleration values for each block. When subjects practiced the movement task, the three variables measuring practice-related changes improved to a similar extent during real and sham iTBS whereas cortical excitability increased only during real iTBS. In a further group of five healthy subjects we investigated the effect of real and sham iTBS on changes in motor performance after a longer task practice and found no significant changes in motor performance and retention after real and sham iTBS. From our results overall we conclude that in healthy subjects iTBS applied to the primary motor cortex leaves practice-related changes in an index finger abduction task unaffected. We suggest that iTBS delivered over the primary motor cortex is insufficient to alter motor performance because early motor learning probably engages a wide cortical and subcortical network.

Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

Science.gov (United States)

Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

2016-11-01

The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

Science.gov (United States)

Heck, Julie A; Meng, Xiao; Frick, David N

2009-04-01

Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

Energy Technology Data Exchange (ETDEWEB)

Jursinic, Paul A., E-mail: pjursinic@wmcc.org [West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

2015-10-15

Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms that had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.

Stimulation of DNA synthesis by 340nm/ 351nm UV laser irradiation

International Nuclear Information System (INIS)

Meldrum, R.A.; Wharton, C.W.

1991-01-01

During preliminary experiments designed to test the feasibility of using a 'caged' DNA break trapping agent, the authors observed a stimulation of incorporation of 3 H-thymidine into DNA when cells were irradiated with low doses (100-1000J/m 2 ) of 351nm UV laser irradiation. This wavelength is used to photolyse 'caged' dideoxynucleotides in our fast time course measurements of DNA repair in mammalian cells. The dose at which this stimulation was observed is well below that at which measurable damage is detected. (author)

A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

Science.gov (United States)

Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

2017-07-01

This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order

Effect of Fast Neutron to MA/PU Burning/Transmutation Characteristic Using a Fast Reactor

International Nuclear Information System (INIS)

Marsodi; Lasman, As Natio; Kimamoto, A.; Marsongkohadi; Zaki, S.

2003-01-01

MA/Pu burning/transmutation has been studied and evaluated using fast neutrons. Generally, neutron density at this fast burner reactor and transmutation has spectrum energy level around 0.2 MeV with wide enough variation, i.e. from low neutron spectrum to its peak is 0.2 MeV. This neutron spectrum energy level depends on the kind of cooler material or fuel used. Neutron spectrum higher than fast power reactor neutron spectrum is found by means of changing oxide fuel by metallic fuel and changing natrium cooler material by metallic or gas cooler material. This evaluation is conducted by various variations in accordance with the kind of fuel or cooler, MA/Pu fractions and fuel comparison fraction with respect to its cooler in order to get better neutron usage and MA/Pu burning speed. Reactor calculation evaluation in this paper was conducted with 26-group nuclear data cross section energy spectrum. The main purpose of the discussion is to know the effect of fast neutrons to burning/transmutation MA/Pu using fast neutrons

Relaxation oscillations in stimulated Raman scattering

International Nuclear Information System (INIS)

Kachen, G.I.; Lowdermilk, W.H.

1977-01-01

Light pulses created by stimulated Raman scattering having been found to exhibit a complex time dependence which resembles relaxation oscillations. A focused laser pulse generated both forward and backward Raman emissions which appeared as a series of pulses with durations much shorter than the incident laser pulse. Time dependence of the Raman emission was observed directly by use of a streak camera. The number of observed pulses increased with the intensity of the incident pulse, while separation of the pulses in time depended on the length of the focal region. Beam focusing was incorporated in the coupled wave equations for stimulated Raman scattering. These rate equations were then solved numerically, and the results are in good qualitative agreement with the experimental observations. The short Raman pulses are created by a process associated with depletion of the incident laser pulse. This process occurs under a broad range of conditions

Fast reactor development strategy targets study in China

International Nuclear Information System (INIS)

Xu Mi

2008-01-01

China is a big developing Country who needs a huge energy resources and a rapid growing rate. Considering energy resources limited and environment issues it is sure that the nuclear energy will be becoming one of the main energy resources. The Government has decided to develop the nuclear power capacity to 40 GW in 2020. It is envisaged that it will reach to 240 GW in 2050. It is stimulate us to consider conscientiously the development of the fast breeder reactor's and related closed nuclear fuel cycle by the limitation of Uranium resources and uncertainties of international Uranium market. Followings are the proposed strategic targets of fast reactor development in China. (1) To realize the operation of commercial fast breeder reactors with an unit size of 800-900 MWe and one site-multi reactors in 2030. (2) To develop the nuclear power capacity to 240 GW in 2050. (3) To replace step by step the fossil fuel utilization in large scale by nuclear energy beyond 2050. (authors)

Energy dependence of average half-life of delayed neutron precursors in fast neutron induced fission of 235U and 236U

International Nuclear Information System (INIS)

Isaev, S.G.; Piksaikin, L.E.; Kazakov, L.E.; Tarasko, M.Z.

2000-01-01

The measurements of relative abundances and periods of delayed neutrons from fast neutron induced fission of 235 U and 236 U have been made at the electrostatic accelerator CG-2.5 at IPPE. The preliminary results were obtained and discussed in the frame of the systematics of the average half-life of delayed neutron precursors. It was shown that the average half-life value in both reactions depends on the energy of primary neutrons [ru

Preparation of the fast setting and degrading Ca–Si–Mg cement with both odontogenesis and angiogenesis differentiation of human periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Yi-Wen [Graduate Institute of Clinical Medical Science, China Medical University, Taichung City, Taiwan (China); 3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China); Hsu, Tuan-Ti [Institute of Oral Science, Chung Shan Medical University, Taichung City, Taiwan (China); Wang, Kan [H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Shie, Ming-You, E-mail: eviltacasi@gmail.com [3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China)

2016-03-01

Develop a fast setting and controllable degrading magnesium–calcium silicate cement (Mg–CS) by sol–gel, and establish a mechanism using Mg ions to stimulate human periodontal ligament cells (hPDLs) are two purposes of this study. We have used the diametral tensile strength measurement to obtain the mechanical strength and stability of Mg–CS cement; in addition, the cement degradation properties is realized by measuring the releasing amount of Si and Mg ions in the simulated body fluid. The other cell characteristics of hPDLs, such as proliferation, differentiation and mineralization were examined while hPDLs were cultured on specimen surfaces. This study found out the degradation rate of Mg–CS cements depends on the Mg content in CS. Regarding in vitro bioactivity; the CS cements were covered with abundant clusters of apatite spherulites after immersion of 24 h, while less apatite spherulites were formatted on the Mg-rich cement surfaces. In addition, the authors also explored the effects of Mg ions on the odontogenesis and angiogenesis differentiation of hPDLs in comparison with CS cement. The proliferation, alkaline phosphatase, odontogenesis-related genes (DSPP and DMP-1), and angiogenesis-related protein (vWF and ang-1) secretion of hPDLs were significantly stimulated when the Mg content of the specimen was increased. The results in this study suggest that Mg–CS materials with this modified composition could stimulate hPDLs behavior and can be good bioceramics for bone substitutes and hard tissue regeneration applications as they stimulate odontogenesis/angiogenesis. - Highlights: • The fast setting and degrading Mg–CS cement was synthesized by sol–gel. • Promoted proliferation of hPDLs on Mg–CS specimens • Mg–CS can degrade and release Si and Mg ions into SBF. • Up-regulation of odontogenic and angiogenic of hPDLs • Mg–CS may be good bone substitutes for hard tissue regeneration applications.

Preparation of the fast setting and degrading Ca–Si–Mg cement with both odontogenesis and angiogenesis differentiation of human periodontal ligament cells

International Nuclear Information System (INIS)

Chen, Yi-Wen; Hsu, Tuan-Ti; Wang, Kan; Shie, Ming-You

2016-01-01

Develop a fast setting and controllable degrading magnesium–calcium silicate cement (Mg–CS) by sol–gel, and establish a mechanism using Mg ions to stimulate human periodontal ligament cells (hPDLs) are two purposes of this study. We have used the diametral tensile strength measurement to obtain the mechanical strength and stability of Mg–CS cement; in addition, the cement degradation properties is realized by measuring the releasing amount of Si and Mg ions in the simulated body fluid. The other cell characteristics of hPDLs, such as proliferation, differentiation and mineralization were examined while hPDLs were cultured on specimen surfaces. This study found out the degradation rate of Mg–CS cements depends on the Mg content in CS. Regarding in vitro bioactivity; the CS cements were covered with abundant clusters of apatite spherulites after immersion of 24 h, while less apatite spherulites were formatted on the Mg-rich cement surfaces. In addition, the authors also explored the effects of Mg ions on the odontogenesis and angiogenesis differentiation of hPDLs in comparison with CS cement. The proliferation, alkaline phosphatase, odontogenesis-related genes (DSPP and DMP-1), and angiogenesis-related protein (vWF and ang-1) secretion of hPDLs were significantly stimulated when the Mg content of the specimen was increased. The results in this study suggest that Mg–CS materials with this modified composition could stimulate hPDLs behavior and can be good bioceramics for bone substitutes and hard tissue regeneration applications as they stimulate odontogenesis/angiogenesis. - Highlights: • The fast setting and degrading Mg–CS cement was synthesized by sol–gel. • Promoted proliferation of hPDLs on Mg–CS specimens • Mg–CS can degrade and release Si and Mg ions into SBF. • Up-regulation of odontogenic and angiogenic of hPDLs • Mg–CS may be good bone substitutes for hard tissue regeneration applications.

Fast neutrino flavor conversions near the supernova core with realistic flavor-dependent angular distributions

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Basudeb; Sen, Manibrata [Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400005 (India); Mirizzi, Alessandro, E-mail: bdasgupta@theory.tifr.res.in, E-mail: alessandro.mirizzi@ba.infn.it, E-mail: manibrata.sen@gmail.com [Dipartimento Interateneo di Fisica ' Michelangelo Merlin' , Via Amendola 173, 70126 Bari (Italy)

2017-02-01

It has been recently pointed out that neutrino fluxes from a supernova can show substantial flavor conversions almost immediately above the core. Using linear stability analyses and numerical solutions of the fully nonlinear equations of motion, we perform a detailed study of these fast conversions , focussing on the region just above the supernova core. We carefully specify the instabilities for evolution in space or time, and find that neutrinos travelling towards the core make fast conversions more generic, i.e., possible for a wider range of flux ratios and angular asymmetries that produce a crossing between the zenith-angle spectra of ν {sub e} and ν-bar {sub e} . Using fluxes and angular distributions predicted by supernova simulations, we find that fast conversions can occur within tens of nanoseconds, only a few meters away from the putative neutrinospheres. If these fast flavor conversions indeed take place, they would have important implications for the supernova explosion mechanism and nucleosynthesis.

Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults.

Science.gov (United States)

Gonzalez, Javier T; Richardson, Judith D; Chowdhury, Enhad A; Koumanov, Francoise; Holman, Geoffrey D; Cooper, Scott; Thompson, Dylan; Tsintzas, Kostas; Betts, James A

2018-02-15

In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue. In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue. The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt. Insulin-stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole-body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down-regulation to prevent excessive de novo lipogenesis. This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty-nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; ≥700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin-stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up-regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97-1.30) versus 0.80 (95% CI: 0.64-0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33-2.16) versus 1.09 (95% CI: 0.67-1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

Science.gov (United States)

Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2014-01-01

Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.

Directory of Open Access Journals (Sweden)

Mikkel Holm Vendelbo

Full Text Available Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR, a key regulator of cell growth.Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.

Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

Science.gov (United States)

Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-25

Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

OpenAIRE

Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

2010-01-01

Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine

DEFF Research Database (Denmark)

Orskov, C; Jeppesen, J; Madsbad, S

1991-01-01

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration...... integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed....... In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All...

Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.

Directory of Open Access Journals (Sweden)

José Luis Vargas Luna

Full Text Available Transcutaneous electrical stimulation can depolarize nerve or muscle cells applying impulses through electrodes attached on the skin. For these applications, the electrode-skin impedance is an important factor which influences effectiveness. Various models describe the interface using constant or current-depending resistive-capacitive equivalent circuit. Here, we develop a dynamic impedance model valid for a wide range stimulation intensities. The model considers electroporation and charge-dependent effects to describe the impedance variation, which allows to describe high-charge pulses. The parameters were adjusted based on rectangular, biphasic stimulation pulses generated by a stimulator, providing optionally current or voltage-controlled impulses, and applied through electrodes of different sizes. Both control methods deliver a different electrical field to the tissue, which is constant throughout the impulse duration for current-controlled mode or have a very current peak for voltage-controlled. The results show a predominant dependence in the current intensity in the case of both stimulation techniques that allows to keep a simple model. A verification simulation using the proposed dynamic model shows coefficient of determination of around 0.99 in both stimulation types. The presented method for fitting electrode-skin impedance can be simple extended to other stimulation waveforms and electrode configuration. Therefore, it can be embedded in optimization algorithms for designing electrical stimulation applications even for pulses with high charges and high current spikes.

Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis.

Science.gov (United States)

Kent, Alexander R; Min, Xiaoyi; Hogan, Quinn H; Kramer, Jeffery M

2018-04-01

The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing. The transmembrane potential was measured along the neuron to determine the effect of stimulation on intrinsic activity across stimulation parameters, cell location/orientation, and membrane properties. The model was validated by showing close correspondence in action potential (AP) characteristics and firing patterns when compared to experimental measurements. Subsequently, the model output demonstrated that T-junction filtering was amplified with DRG stimulation, thereby blocking afferent signaling, with cathodic stimulation at amplitudes of 2.8-5.5 × stimulation threshold and frequencies above 2 Hz. This amplified filtering was dependent on the presence of calcium and calcium-dependent small-conductance potassium channels, which produced a hyperpolarization offset in the soma, stem, and T-junction with repeated somatic APs during stimulation. Additionally, DRG stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with cathodic or anodic stimulation at amplitudes of 3-11 × threshold and frequencies above 2 Hz. These effects were dependent on the stem axon being relatively close to and oriented toward a stimulating contact. These results align with the working hypotheses on the mechanisms of DRG stimulation, and indicate the importance of stimulation amplitude, polarity, and cell location/orientation on neuronal responses. © 2018 International Neuromodulation Society.

Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.

Science.gov (United States)

Shah, Faraaz Ali; Singamsetty, Srikanth; Guo, Lanping; Chuan, Byron W; McDonald, Sherie; Cooper, Bryce A; O'Donnell, Brett J; Stefanovski, Darko; Wice, Burton; Zhang, Yingze; O'Donnell, Christopher P; McVerry, Bryan J

2018-03-01

Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis. Published by Elsevier Inc.

Bayesian neural adjustment of inhibitory control predicts emergence of problem stimulant use.

Science.gov (United States)

Harlé, Katia M; Stewart, Jennifer L; Zhang, Shunan; Tapert, Susan F; Yu, Angela J; Paulus, Martin P

2015-11-01

Bayesian ideal observer models quantify individuals' context- and experience-dependent beliefs and expectations about their environment, which provides a powerful approach (i) to link basic behavioural mechanisms to neural processing; and (ii) to generate clinical predictors for patient populations. Here, we focus on (ii) and determine whether individual differences in the neural representation of the need to stop in an inhibitory task can predict the development of problem use (i.e. abuse or dependence) in individuals experimenting with stimulants. One hundred and fifty-seven non-dependent occasional stimulant users, aged 18-24, completed a stop-signal task while undergoing functional magnetic resonance imaging. These individuals were prospectively followed for 3 years and evaluated for stimulant use and abuse/dependence symptoms. At follow-up, 38 occasional stimulant users met criteria for a stimulant use disorder (problem stimulant users), while 50 had discontinued use (desisted stimulant users). We found that those individuals who showed greater neural responses associated with Bayesian prediction errors, i.e. the difference between actual and expected need to stop on a given trial, in right medial prefrontal cortex/anterior cingulate cortex, caudate, anterior insula, and thalamus were more likely to exhibit problem use 3 years later. Importantly, these computationally based neural predictors outperformed clinical measures and non-model based neural variables in predicting clinical status. In conclusion, young adults who show exaggerated brain processing underlying whether to 'stop' or to 'go' are more likely to develop stimulant abuse. Thus, Bayesian cognitive models provide both a computational explanation and potential predictive biomarkers of belief processing deficits in individuals at risk for stimulant addiction. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please

Optically stimulated luminescence from quartz measured using the linear modulation technique

International Nuclear Information System (INIS)

Bulur, E.; Boetter-Jensen, L.; Murray, A.S.

2000-01-01

The optically stimulated luminescence (OSL) from heated natural quartz has been investigated using the linear modulation technique (LMT), in which the excitation light intensity is increased linearly during stimulation. In contrast to conventional stimulation, which usually produces a monotonically decreasing signal, linearly increasing the stimulation power gives peaks in the signal as a function of time. In cases where the OSL signal contains more than one component, the linear increase in power of the stimulation light may result in a curve containing overlapping peaks, where the most easily stimulated component occurs at a shorter time. This allows the separation of the overlapping OSL components, which are assumed to originate from different traps. The LM-OSL curve from quartz shows an initial peak followed by a broad one. Deconvolution using curve fitting has shown that the composite OSL curve from quartz can be approximated well by using a linear combination of first-order peaks. In addition to the three known components, i.e. fast, medium and slow components from continuous-wave-OSL studies, an additional slow component is also identified for the first time. The dose responses and thermal stabilities of the various components are also studied

The effect of deep brain stimulation on the speech motor system.

Science.gov (United States)

Mücke, Doris; Becker, Johannes; Barbe, Michael T; Meister, Ingo; Liebhart, Lena; Roettger, Timo B; Dembek, Till; Timmermann, Lars; Grice, Martine

2014-08-01

Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the coordination of oral and glottal articulation. Sixteen native-speaking German adults with essential tremor, between 26 and 86 years old, with and without chronic deep brain stimulation of the nucleus ventralis intermedius and 12 healthy, age-matched subjects were recorded performing a fast syllable repetition task (/papapa/, /tatata/, /kakaka/). Syllable duration and voicing-to-syllable ratio as well as parameters related directly to consonant production, voicing during constriction, and frication during constriction were measured. Voicing during constriction was greater in subjects with essential tremor than in controls, indicating a perseveration of voicing into the voiceless consonant. Stimulation led to fewer voiceless intervals (voicing-to-syllable ratio), indicating a reduced degree of glottal abduction during the entire syllable cycle. Stimulation also induced incomplete oral closures (frication during constriction), indicating imprecise oral articulation. The detrimental effect of stimulation on the speech motor system can be quantified using acoustic measures at the subsyllabic level.

Metallic taste from electrical and chemical stimulation.

Science.gov (United States)

Lawless, Harry T; Stevens, David A; Chapman, Kathryn W; Kurtz, Anne

2005-03-01

A series of three experiments investigated the nature of metallic taste reports after stimulation with solutions of metal salts and after stimulation with metals and electric currents. To stimulate with electricity, a device was fabricated consisting of a small battery affixed to a plastic handle with the anode side exposed for placement on the tongue or oral tissues. Intensity of taste from metals and batteries was dependent upon the voltage and was more robust in areas dense in fungiform papillae. Metallic taste was reported from stimulation with ferrous sulfate solutions, from metals and from electric stimuli. However, reports of metallic taste were more frequent when the word 'metallic' was presented embedded in a list of choices, as opposed to simple free-choice labeling. Intensity decreased for ferrous sulfate when the nose was occluded, consistent with a decrease in retronasal smell, as previously reported. Intensity of taste evoked by copper metal, bimetallic stimuli (zinc/copper) or small batteries (1.5-3 V) was not affected by nasal occlusion. This difference suggests two distinct mechanisms for evocation of metallic taste reports, one dependent upon retronasal smell and a second mediated by oral chemoreceptors.

Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

Directory of Open Access Journals (Sweden)

Terry B Huff

2011-03-01

Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

A gamma/neutron-discriminating, Cooled, Optically Stimulated Luminescence (COSL) dosemeter

International Nuclear Information System (INIS)

Eschbach, P.A.; Miller, S.D.

1992-07-01

The Cooled Optically Stimulated Luminescence (COSL) of CaF 2 :Mn (grain sizes from 0.1 to 100 microns) powder embedded in a hydrogenous matrix is reported as a function of fast-neutron dose. When all the CaF 2 :Mn grains are interrogated at once, the COSL plastic dosemeters have a minimum detectable limit of 1 cSv fast neutrons; the gamma component from the bare 252 cf exposure was determined with a separate dosemeter. We report here on a proton-recoil-based dosemeter that generates pulse height spectra, much like the scintillator of Hornyak, (2) to provide information on both the neutron and gamma dose

Inhibiting effects of Streptococcus salivarius on competence-stimulating peptide-dependent biofilm formation by Streptococcus mutans.

Science.gov (United States)

Tamura, S; Yonezawa, H; Motegi, M; Nakao, R; Yoneda, S; Watanabe, H; Yamazaki, T; Senpuku, H

2009-04-01

The effects of Streptococcus salivarius on the competence-stimulating peptide (CSP)-dependent biofilm formation by Streptococcus mutans were investigated. Biofilms were grown on 96-well microtiter plates coated with salivary components in tryptic soy broth without dextrose supplemented with 0.25% sucrose. Biofilm formations were stained using safranin and quantification of stained biofilms was performed by measuring absorbance at 492 nm. S. mutans formed substantial biofilms, whereas biofilms of S. salivarius were formed poorly in the medium conditions used. Furthermore, in combination cultures, S. salivarius strongly inhibited biofilm formation when cultured with S. mutans. This inhibition occurred in the early phase of biofilm formation and was dependent on inactivation of the CSP of S. mutans, which is associated with competence, biofilm formation, and antimicrobial activity of the bacterium, and is induced by expression of the comC gene. Comparisons between the S. mutans clinical strains FSC-3 and FSC-3DeltaglrA in separate dual-species cultures with S. salivarius indicated that the presence of the bacitracin transport ATP-binding protein gene glrA caused susceptibility to inhibition of S. mutans biofilm formation by S. salivarius, and was also associated with the regulation of CSP production by com gene-dependent quorum sensing systems. It is considered that regulation of CSP by glrA in S. mutans and CSP inactivation by S. salivarius are important functions for cell-to-cell communication between biofilm bacteria and oral streptococci such as S. salivarius. Our results provide useful information for understanding the ecosystem of oral streptococcal biofilms, as well as the competition between and coexistence of multiple species in the oral cavity.

Reduction in cortical parvalbumin expression due to intermittent theta-burst stimulation correlates with maturation of the perineuronal nets in young rats.

Science.gov (United States)

Mix, Annika; Hoppenrath, Kathrin; Funke, Klaus

2015-01-01

We recently showed that intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast-spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age-dependent. Conscious Sprague-Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS-related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8-9%) did not change with age in sham-controls and also the increase in cortical c-Fos expression induced by iTBS was not principally age-dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35 d to enable activity-dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity. © 2014 Wiley Periodicals, Inc.

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

Science.gov (United States)

Groppa, S.; Oliviero, A.; Eisen, A.; Quartarone, A.; Cohen, L.G.; Mall, V.; Kaelin-Lang, A.; Mima, T.; Rossi, S.; Thickbroom, G.W.; Rossini, P.M.; Ziemann, U.; Valls-Solé, J.; Siebner, H.R.

2016-01-01

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. PMID:22349304

Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

DEFF Research Database (Denmark)

K, Henningsen,; Woldbye, David Paul Drucker; Wiborg, Ove

2013-01-01

Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown...

Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation.

Science.gov (United States)

Tsukamoto, Hiroki; Takeuchi, Shino; Kubota, Kanae; Kobayashi, Yohei; Kozakai, Sao; Ukai, Ippo; Shichiku, Ayumi; Okubo, Misaki; Numasaki, Muneo; Kanemitsu, Yoshitomi; Matsumoto, Yotaro; Nochi, Tomonori; Watanabe, Kouichi; Aso, Hisashi; Tomioka, Yoshihisa

2018-05-14

Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

How to personalize ovarian stimulation in clinical practice.

Science.gov (United States)

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

NARCIS (Netherlands)

van Kempen, Anne A. M. W.; van der Crabben, Saskia N.; Ackermans, Mariëtte T.; Endert, Erik; Kok, Joke H.; Sauerwein, Hans P.

2006-01-01

In preterm infants, both hypo- and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis.

Optimal number of stimulation contacts for coordinated reset neuromodulation

Science.gov (United States)

Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239

Fasting and meal-induced CCK and PP secretion following intragastric balloon treatment for obesity

NARCIS (Netherlands)

Mathus-Vliegen, Elisabeth M. H.; de Groot, Gerrit H.

2013-01-01

Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. We aimed to investigate whether intragastric balloon treatment affects satiety through effects on fasting and meal-stimulated cholecystokinin (CCK) and pancreatic polypeptide (PP) secretion. Patients

Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.

Science.gov (United States)

Sanzgiri, R P; Araque, A; Haydon, P G

1999-11-05

Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors. Copyright 1999 John Wiley & Sons, Inc.

Using brain-computer interfaces and brain-state dependent stimulation as tools in cognitive neuroscience

Directory of Open Access Journals (Sweden)

Ole eJensen

2011-05-01

Full Text Available Large efforts are currently being made to develop and improve online analysis of brain activity which can be used e.g. for brain-computer interfacing (BCI. A BCI allows a subject to control a device by willfully changing his/her own brain activity. BCI therefore holds the promise as a tool for aiding the disabled and for augmenting human performance. While technical developments obviously are important, we will here argue that new insight gained from cognitive neuroscience can be used to identify signatures of neural activation which reliably can be modulated by the subject at will. This review will focus mainly on oscillatory activity in the alpha band which is strongly modulated by changes in covert attention. Besides developing BCIs for their traditional purpose, they might also be used as a research tool for cognitive neuroscience. There is currently a strong interest in how brain state fluctuations impact cognition. These state fluctuations are partly reflected by ongoing oscillatory activity. The functional role of the brain state can be investigated by introducing stimuli in real time to subjects depending on the actual state of the brain. This principle of brain-state dependent stimulation may also be used as a practical tool for augmenting human behavior. In conclusion, new approaches based on online analysis of ongoing brain activity are currently in rapid development. These approaches are amongst others informed by new insight gained from EEG/MEG studies in cognitive neuroscience and hold the promise of providing new ways for investigating the brain at work.

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Science.gov (United States)

Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo; Lee, Andrew; Tift, Michael S; Tavoni, Stephen K; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

DEFF Research Database (Denmark)

Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

2014-01-01

signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

Optimized choice of method for determining proliferation response of peripheral lymphocytes to mitogens in low dose irradiation with cyclotron fast neutrons

International Nuclear Information System (INIS)

Refka, Z.; Svec, M.; Aganov, P.; Svoboda, V.; Podzimek, F.

1989-01-01

Heparinized venous blood sampled from seven donors was irradiated with doses of 0.1; 0.25; 0.5; 1.0; 2.0 and 3.0 Gy of fast neutrons of a mean energy of 7.6 MeV using the U 120 M isochronous cyclotron. A non-irradiated control sample was also prepared. A lymphoblastic transformation test was conducted with both the intact and irradiated samples. The samples were cultivated in the RPMI-1640 medium with and without a mitogen addition, this in five time variants, viz., for 48, 72, 90, 96 and 120 hours. The proliferation was monitored of lymphocytes stimulated with mitogens PHA, CON-A and PWM in dependence on the time of cultivation and on the radiation dose. The dose dependent relative response was also studied of the irradiated lymphocytes. (E.J.). 8 figs., 1 tab., 18 refs

Optimal number of stimulation contacts for coordinated reset neuromodulation

Directory of Open Access Journals (Sweden)

Borys eLysyansky

2013-07-01

Full Text Available In this computational study we investigatecoordinated reset (CR neuromodulation designed for an effective controlof synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchronycharacteristic for several neurological disorders. We studyhow many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sitesmay significantly prolong the post-stimulation desynchronized transientafter the stimulation is completely switched off. This can, in turn,reduce the amount of the administered stimulation current for theintermittent ON-OFF CR stimulation protocol, where time intervalswith stimulation ON are recurrently followed by time intervals withstimulation OFF. In addition, we found that the optimal number ofstimulation sites essentially depends on how strongly the administeredcurrent decays within the neuronal tissue with increasing distancefrom the stimulation site. In particular, for a broad spatial stimulationprofile, i.e., for a weak spatial decay rate of the stimulation current,CR stimulation can optimally be delivered via a small number of stimulationsites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation.

Size dependent emission stimulation in ZnO nanosheets

International Nuclear Information System (INIS)

Torchynska, T.V.; El Filali, B.

2014-01-01

Photoluminescence (PL), X ray diffraction (XRD) and Raman scattering have been studied in crystalline ZnO nanosheets (NSs) of different sizes, estimated by scanning electronic microscopy (SEM). ZnO NSs with the size from the range of 60–600 nm were created by the electrochemical (anodization) method and followed thermal annealing at 400 °C for 2 h in ambient air. XRD study confirms the wurtzite structure of ZnO NSs and has revealed that the lattice parameters increase monotonically with decreasing NS sizes. Simultaneously the intensity of a set of Raman peaks increases and Raman peaks shift into the low energy range. The surface phonon has been detected in smallest size ZnO NSs. Two types of PL bands deal with a set of phonon replicas of free excitons and the defect related emission have been detected in ZnO NSs. The intensity enhancement of exciton- and defect-related PL bands with decreasing ZnO NS sizes has been detected. The intensity stimulation of exciton-related PL bands is attributed to the realization of the week confinement and the exciton-light coupling with the formation of polariton in small size ZnO NSs of 67–170 nm. The intensity rising of defect-related PL bands is attributed to the concentration enlargement of surface defects when the surface to volume ration increases at decreasing ZnO NS sizes. Numerical simulations of radiative lifetimes and exciton radiative recombination rates in ZnO NSs for different emission wavelengths have been done using the exciton-light coupling model. Then the experimental and numerically simulated PL results have been compared and discussed. - Highlights: • Optical and structural investigations of the ZnO nanosheets with the sizes 60–600 nm. • The enlargement of interplanar distances in the wurtzite ZnO crystal lattice is detected. • The change of optic phonon energy and surface phonon appearing are reveled. • ZnO emission stimulation at the week confinement and electron-light coupling with the

Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

International Nuclear Information System (INIS)

Richter, E.A.; Hansen, S.A.; Hansen, B.F.

1988-01-01

The extent to which muscle glycogen concentrations can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 μU/ml insulin and 11-13 mM glucose increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased from 34.9 μmol·g -1 ·h -1 at 0 h to 7.5 after 7 h of perfusion. During the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[ 14 C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal

A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee.

Science.gov (United States)

Groppa, S; Oliviero, A; Eisen, A; Quartarone, A; Cohen, L G; Mall, V; Kaelin-Lang, A; Mima, T; Rossi, S; Thickbroom, G W; Rossini, P M; Ziemann, U; Valls-Solé, J; Siebner, H R

2012-05-01

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle

NARCIS (Netherlands)

van Bolhuis, A.I.; Holsheimer, J.; Savelsberg, H.H.C.M.

2001-01-01

Electrical stimulation of peripheral nerve results in a motor-unit recruitment order opposite to that attained by natural neural control, i.e. from large, fast-fatiguing to progressively smaller, fatigue-resistant motor-units. Yet animal studies involving physiological exercise protocols of low

Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation

OpenAIRE

Wang, Gene-Jack; Volkow, Nora D.; Telang, Frank; Jayne, Millard; Ma, Yeming; Pradhan, Kith; Zhu, Wei; Wong, Christopher T.; Thanos, Panayotis K.; Geliebter, Allan; Biegon, Anat; Fowler, Joanna S.

2009-01-01

Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[18F]fluoro-D-glucose (18FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insul...

What are the benefits and the pitfalls of preoperative fasting?

Science.gov (United States)

Webb, Katherine

Preoperative fasting has been a traditional practice for many years to reduce the risk of aspiration while the patient is under general anaesthetic and to eliminate the risk of postoperative nausea and vomiting. Although it is generally accepted that fasting is beneficial, the fasting regimens that patients undergo are not dependent on the individual patient or the timing of their operation.

Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism

Science.gov (United States)

Hamdi, M M; Mutungi, G

2011-01-01

Abstract Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and α-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression. PMID:21606113

Respiratory Responses to Stimulation of Branchial Vagus Nerve Ganglia of a Teleost Fish

NARCIS (Netherlands)

Ballintijn, C.M.; Luiten, P.G.M.

1983-01-01

The effects of electrical stimulation of epibranchial vagus ganglia upon respiration of the carp were investigated. Single shocks evoked fast twitch responses in a number of respiratory muscles with latencies around 18 msec to the beginning and 30-35 msec to the peak of activity. Shocks given during

Fast Reactors and Nuclear Nonproliferation

International Nuclear Information System (INIS)

Avrorina, E.N.; Chebeskovb, A.N.

2013-01-01

Conclusion remarks: 1. Fast reactor start-up with U-Pu fuel: – dependent on thermal reactors, – no needs in U enrichment, – needs in SNF reprocessing, – Pu is a little suitable for NED, – practically impossible gun-type NED, – difficulties for implosion-type NED: necessary tests, advanced technologies, etc. – Pu in blankets is similar to WPu by isotopic composition, – Use of blanket for production isotopes (e.g. 233 U), – Combined reprocessing of SNF: altogether blanket and core, – Blanket elimination: decrease in Pu production – No pure Pu separation. 2. Fast reactor start-up with U fuel: - Needs in both U enrichment and SNF reprocessing, - Independent of thermal reactors, - Good Pu bred in the core let alone blankets, - NED of simple gun-type design, - Increase of needs in SWU, - Increased demands in U supply. 3. Fast reactors for export: - Uranium shortage, - To replace thermal reactors in future, - No blankets (depends on the country, though), - Fuel supply and SNF take back, - International centers for rendering services of NFC. Time has come to remove from FRs and their NFC the label unfairly identifying them as the most dangerous installations of nuclear power from the standpoint of being a proliferation problem

KCl stimulation increases norepinephrine transporter function in PC12 cells.

Science.gov (United States)

Mandela, Prashant; Ordway, Gregory A

2006-09-01

The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

Science.gov (United States)

Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

2014-01-01

Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

Science.gov (United States)

Meiron, Oded; Lavidor, Michal

2013-05-01

Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

Science.gov (United States)

Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

2016-01-01

A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Fasting and meal-induced CCK and PP secretion following intragastric balloon treatment for obesity.

Science.gov (United States)

Mathus-Vliegen, Elisabeth M H; de Groot, Gerrit H

2013-05-01

Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. We aimed to investigate whether intragastric balloon treatment affects satiety through effects on fasting and meal-stimulated cholecystokinin (CCK) and pancreatic polypeptide (PP) secretion. Patients referred for obesity treatment were randomised to 13 weeks of sham treatment followed by 13 weeks of balloon treatment (group 1; sham/balloon) or to twice a 13-week period of balloon treatment (group 2; balloon/balloon). Blood samples were taken for fasting and meal-stimulated CCK and PP levels at the start (T0) and after 13 (T1) and 26 (T2) weeks. Patients filled out visual analogue scales (VAS) to assess satiety. Forty-two patients (35 females, body weight 125.1 kg, BMI 43.3 kg/m(2)) participated. In group 1, basal CCK levels decreased but meal-stimulated response remained unchanged after 13 weeks of sham treatment. In group 2, basal and meal-stimulated CCK levels decreased after 13 weeks of balloon treatment. At the end of the second 13-week period, when group 1 had their first balloon treatment, they duplicated the initial 13-week results of group 2, whereas group 2 continued their balloon treatment and reduced meal-stimulated CCK release. Both groups showed reduced meal-stimulated PP secretions at T1 and T2 compared to T0. Changes in diet composition and VAS scores were similar. Improvements in glucose homeostasis partly explained the PP results. The reduced CCK and PP secretion after balloon positioning was unexpected and may reflect delayed gastric emptying induced by the balloon. Improved glucose metabolism partly explained the reduced PP secretion. Satiety and weight loss were not adversely influenced by these hormonal changes.

Transcranial alternating current stimulation (tACS

Directory of Open Access Journals (Sweden)

Andrea eAntal

2013-06-01

Full Text Available Transcranial alternating current stimulation (tACS seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency or desynchronize (e.g. by the application of several frequencies cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the ripple range induces intensity dependent inhibition or excitation in the motor cortex most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

The implications of Ramadan fasting for human health and well-being.

Science.gov (United States)

Alkandari, Jasem Ramadan; Maughan, Ronald J; Roky, Rachida; Aziz, Abdul Rashid; Karli, Umid

2012-01-01

Islamic Ramadan is a 29-30 day fast in which food, fluids, medications, drugs and smoking are prohibited during the daylight hours which can be extended between 13 and 18 h · day(-1) depending on the geographical location and season. The majority of health-specific findings related to Ramadan fasting are mixed. The likely causes for these heterogeneous findings lie in the amount of daily time of fasting, number of subjects who smoke, take oral medications, and/or receive intravenous fluids, in the type of food and eating habits and in changes in lifestyle. During Ramadan fasting, glucose homeostasis is maintained by meals taken during night time before dawn and by liver glycogen stores. Changes in serum lipids are variable and depend on the quality and quantity of food intake, physical activity and exercise, and changes in body weight. Compliant, well-controlled type II diabetics may observe Ramadan fasting, but fasting is not recommended for type I, noncompliant, poorly controlled and pregnant diabetics. There are no adverse effects of Ramadan fasting on respiratory and cardiovascular systems, haematologic profile, endocrine, and neuropsychiatric functions. Although Ramadan fasting is safe for all healthy individuals, those with various diseases should consult their physicians and follow medical and scientific recommendations.

FAST: FAST Analysis of Sequences Toolbox

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Travis J. Lawrence

2015-05-01

Full Text Available FAST (FAST Analysis of Sequences Toolbox provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU’s Not Unix Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics makes FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format. Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought.

Adrenergic influence on pentagastrin and bethanechol stimulated gastric acid secretion in dogs with gastric fistula

DEFF Research Database (Denmark)

Hovendal, C; Bech, K; Gottrup, F

1984-01-01

. The inhibitory effect of isoprenaline on pentagastrin stimulated acid secretion showed the characteristics of competitive type and on bethanechol stimulated acid secretion of non competitive type. An increasing and dose-dependent stimulation of bethanechol stimulated gastric acid secretion was found for dopamine...

Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

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Damián Hernández

2016-01-01

Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

The optimal stimulation pattern for skeletal muscle is dependent on muscle length

NARCIS (Netherlands)

Mela, P.; Veltink, Petrus H.; Huijing, P.A.J.B.M.; Salmons, S.; Jarvis, J.C.

2002-01-01

elicited muscle contraction. Such patterns, providing the desired force output with the minimum number of pulses, may reduce muscle fatigue, which has been shown to correlate to the number of pulses delivered. Applications of electrical stimulation to use muscle as a controllable biological actuator

Ability of GLP-1 to decrease food intake is dependent on nutritional status.

Science.gov (United States)

Ronveaux, Charlotte C; de Lartigue, Guillaume; Raybould, Helen E

2014-08-01

Gut-derived glucagon like peptide-1 (GLP-1) acts in the postprandial period to stimulate insulin secretion and inhibit gastrointestinal motor and secretory function; whether endogenous peripheral GLP-1 inhibits food intake is less clear. We hypothesized that GLP-1 inhibits food intake in the fed, but not fasted, state. There is evidence that GLP-1 acts via stimulation of vagal afferent neurons (VAN); we further hypothesized that the satiating effects of endogenous GLP-1 in the postprandial period is determined either by a change in GLP-1 receptor (GLP-1R) expression or localization to different cellular compartments in VAN. Food intake was recorded following administration of GLP-1 (50μg/kg or 100μg/kg) or saline (IP) in Wistar rats fasted for 18h or fasted then re-fed with 3g chow. GLP-1R protein expression and localization on VAN were determined by immunocytochemistry and immunoblots in animals fasted for 18h or fasted then re-fed for 40min. GLP-1R mRNA level was detected in animals fasted for 18h or fasted and re-fed ad libitum for 2h. GLP-1 (100μg/kg) significantly reduced 40min food intake by 38% in re-fed but not fasted rats (pfasted rats. However, GLP-1R localization to the plasma membrane was significantly increased in VAN by feeding. Feeding changes the ability of peripheral GLP-1 to inhibit food intake. GLP-1Rs are trafficked to the plasma membrane in response to a meal. GLP-1 may play a role in regulating food intake in the postprandial period. Copyright © 2014 Elsevier Inc. All rights reserved.

Concept and canons of fasting in Ayurveda

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H Shripathi Adiga

2013-03-01

Full Text Available Ayurveda, manoeuvres mankind to head a healthy life in order to pursue four-fold bliss. With a view to combat physical and mental annoyances, classics have explicated two-fold therapeutic modalities; langhana/depletion and brihmana/nourishing. Upavasa /fasting is one among ten depletion therapies explained. It is envisioned at all three levels of Ayurvedic therapies- rational/objectively planned, psychological, and spiritual. Fasting is reckoned to be refraining from all forms of food intake for a given period, under supervision of a qualified physician. Acharya Charaka advocates fasting in diseases of milder intensity, in those due to aama (metabolic toxin, after purificatory procedures. Fasting person should avoid beautifying oneself, day sleep, sexual acts, and feasting prior and ulterior to fasting. Fasting is contraindicated in very young, elderly, emaciated, pregnant lady, and shortly after strenuous exercise. The principle avers that fasting kindles metabolic/digestive fire which, in absence of food, brings about paachana of vitiated doshas, thereby riposting health. Sound fasting ensues proper elimination of excretory wastes, clear belch, sweat, and taste for food. Benefits of fasting include lucidity of sense organs, lightness of body and mind, control of diseases, and enthusiasm. Yoga Shastra describes fasting with respect to three levels of food: physical, impressions, and associations and a means to unite three bodies: astral, physical, and causal. Ayurveda thus advocates fasting depending upon the dosha, agni, vaya, kala, and bala of the individual, as a preventive as well as therapeutic modality.

Anal sphincter responses after perianal electrical stimulation

DEFF Research Database (Denmark)

Pedersen, Ejnar; Klemar, B; Schrøder, H D

1982-01-01

By perianal electrical stimulation and EMG recording from the external anal sphincter three responses were found with latencies of 2-8, 13-18 and 30-60 ms, respectively. The two first responses were recorded in most cases. They were characterised by constant latency and uniform pattern, were...... not fatigued by repeated stimulation, were most dependent on placement of stimulating and recording electrodes, and always had a higher threshold than the third response. The third response was constantly present in normal subjects. It had the longest EMG response and the latency decreased with increasing...... stimulation to a minimum of 30-60 ms. This response represented the clinical observable spinal reflex, "the classical anal reflex". The latencies of the two first responses were so short that they probably do not represent spinal reflexes. This was further supported by the effect of epidural anaesthesia which...

Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

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Yong Hyun Kwon

2015-01-01

Full Text Available Transcranial direct current stimulation (tDCS, an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimulator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels (levels 1, 2, 3 of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of moderate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes.

Science.gov (United States)

Raos, B J; Graham, E S; Unsworth, C P

2017-06-01

Astrocytes respond to various stimuli resulting in intracellular Ca 2+ signals that can propagate through organized functional networks. Recent literature calls for the development of techniques that can stimulate astrocytes in a fast and highly localized manner to emulate more closely the characteristics of astrocytic Ca 2+ signals in vivo. In this article we demonstrate, for the first time, how nanosecond UV lasers are capable of reproducibly stimulating Ca 2+ transients in human hNT astrocytes. We report that laser pulses with a beam energy of 4-29 µJ generate transient increases in cytosolic Ca 2+ . These Ca 2+ transients then propagate to adjacent astrocytes as intercellular Ca 2+ waves. We propose that nanosecond laser stimulation provides a valuable tool for enabling the study of Ca 2+ dynamics in human astrocytes at both a single cell and network level. Compared to previously developed techniques nanosecond laser stimulation has the advantage of not requiring loading of photo-caged or -sensitising agents, is non-contact, enables stimulation with a high spatiotemporal resolution and is comparatively cost effective.

Holographically generated structured illumination for cell stimulation in optogenetics

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Schmieder, Felix; Büttner, Lars; Czarske, Jürgen; Torres, Maria Leilani; Heisterkamp, Alexander; Klapper, Simon; Busskamp, Volker

2017-06-01

In Optogenetics, cells, e.g. neurons or cardiac cells, are genetically altered to produce for example the lightsensitive protein Channelrhodopsin-2. Illuminating these cells induces action potentials or contractions and therefore allows to control electrical activity. Thus, light-induced cell stimulation can be used to gain insight to various biological processes. Many optogenetics studies, however, use only full field illumination and thus gain no local information about their specimen. But using modern spatial light modulators (SLM) in conjunction with computer-generated holograms (CGH), cells may be stimulated locally, thus enabling the research of the foundations of cell networks and cell communications. In our contribution, we present a digital holographic system for the patterned, spatially resolved stimulation of cell networks. We employ a fast ferroelectric liquid crystal on silicon SLM to display CGH at up to 1.7 kHz. With an effective working distance of 33 mm, we achieve a focus of 10 μm at a positioning accuracy of the individual foci of about 8 μm. We utilized our setup for the optogenetic stimulation of clusters of cardiac cells derived from induced pluripotent stem cells and were able to observe contractions correlated to both temporal frequency and spatial power distribution of the light incident on the cell clusters.

Sunlight Triggers Cutaneous Lupus through a Colony Stimulating Factor-1 (CSF-1) Dependent Mechanism in MRL-Faslpr mice

Science.gov (United States)

Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T.; Lucas, Julie A.; Rabacal, Whitney A.; Croker, Byron P.; Zong, Xiao-Hua; Stanley, E. Richard; Kelley, Vicki R.

2008-01-01

Sunlight (UVB) triggers cutaneous (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø) -mediated mechanism in MRL-Faslpr mice. By constructing mutant MRL-Faslpr strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex-vivo gene transfer to deliver CSF-1 intra-dermally, we determined that CSF-1 induces CLE in lupus-susceptible, MRL-Faslpr mice, but not in lupus-resistant, BALB/c mice. Notably, UVB incites an increase in Mø, apoptosis in the skin and CLE in MRL-Faslpr, but not in CSF-1-deficient MRL-Faslpr mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Mø that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Faslpr, but not lupus-resistant BALB/c mice. Taken together, we envision CSF-1 as the “match” and lupus-susceptibility as the “tinder” leading to CLE. PMID:18981160

Leucine stimulation of skeletal muscle protein synthesis

International Nuclear Information System (INIS)

Layman, D.K.; Grogan, C.K.

1986-01-01

Previous work in this laboratory has demonstrated a stimulatory effect of leucine on skeletal muscle protein synthesis measured in vitro during catabolic conditions. Studies in other laboratories have consistently found this effect in diaphragm muscle, however, studies examining effects on nitrogen balance or with in vivo protein synthesis in skeletal muscle are equivocal. This experiment was designed to determine the potential of leucine to stimulate skeletal muscle protein synthesis in vivo. Male Sprague-Dawley rats weighing 200 g were fasted for 12 hrs, anesthetized, a jugular cannula inserted, and protein synthesis measured using a primed continuous infusion of 14 C-tyrosine. A plateau in specific activity was reached after 30 to 60 min and maintained for 3 hrs. The leucine dose consisted of a 240 umole priming dose followed by a continuous infusion of 160 umoles/hr. Leucine infusion stimulated protein synthesis in the soleus muscle (28%) and in the red (28%) and white portions (12%) of the gastrocnemius muscle compared with controls infused with only tyrosine. The increased rates of protein synthesis were due to increased incorporation of tyrosine into protein and to decreased specific activity of the free tyrosine pool. These data indicate that infusion of leucine has the potential to stimulate in vivo protein synthesis in skeletal muscles

Onset of fast "ideal" tearing in thin current sheets: Dependence on the equilibrium current profile

Science.gov (United States)

Pucci, F.; Velli, M.; Tenerani, A.; Del Sarto, D.

2018-03-01

In this paper, we study the scaling relations for the triggering of the fast, or "ideal," tearing instability starting from equilibrium configurations relevant to astrophysical as well as laboratory plasmas that differ from the simple Harris current sheet configuration. We present the linear tearing instability analysis for equilibrium magnetic fields which (a) go to zero at the boundary of the domain and (b) contain a double current sheet system (the latter previously studied as a Cartesian proxy for the m = 1 kink mode in cylindrical plasmas). More generally, we discuss the critical aspect ratio scalings at which the growth rates become independent of the Lundquist number S, in terms of the dependence of the Δ' parameter on the wavenumber k of unstable modes. The scaling Δ'(k) with k at small k is found to categorize different equilibria broadly: the critical aspect ratios may be even smaller than L/a ˜ Sα with α = 1/3 originally found for the Harris current sheet, but there exists a general lower bound α ≥ 1/4.

Impact of behavioral control on the processing of nociceptive stimulation

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James W Grau

2012-08-01

Full Text Available How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation, it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation. These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: Controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit. Uncontrollable stimulation also enhances mechanical reactivity (allodynia. We review evidence that training with controllable stimulation engages a BDNF-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin. A model is proposed that assumes nociceptive input is gated at an early stage, within the dorsal horn. his gate is sensitive to current environmental relations (between proprioceptive and nociceptive input, allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain.

Impact of Behavioral Control on the Processing of Nociceptive Stimulation

Science.gov (United States)

Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

2012-01-01

How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

Fast Ion Redistribution and Implications for the Hybrid Regime

International Nuclear Information System (INIS)

Nazikian, R.; Austin, M.E.; Budny, R.V.; Chu, M.S.; Heidbrink, W.W.; Makowski, M.A.; Petty, C.C.; Politzer, P.A.; Solomon, W.M.; Van Zeeland, M.A.

2007-01-01

Time dependent TRANSP analysis indicates that radial redistribution of fast ions is unlikely to affect the central current density in hybrid plasmas sufficient to raise q(0) above unity. The results suggest that some other mechanism other than fast ion transport must be involved in raising q(0) and preventing sawteeth in hybrid plasmas.

Ghrelin stimulates synaptic formation in cultured cortical networks in a dose-dependent manner

NARCIS (Netherlands)

Herzig, K.H.; Stoyanova, Irina; le Feber, Jakob; Rutten, Wim

2013-01-01

Ghrelin was initially related to appetite stimulation and growth hormone secretion. These findings suggest that ghrelin may provide a novel therapeutic strategy for the treatment of disorders related to synaptic impairment.

Effect of Parkinson's Disease in Transcranial Magnetic Stimulation Treatment

Science.gov (United States)

Syeda, Farheen; Magsood, Hamzah; Lee, Erik; El-Gendy, Ahmed; Jiles, David; Hadimani, Ravi

Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury.

Science.gov (United States)

Murray, Lynda M; Edwards, Dylan J; Ruffini, Giulio; Labar, Douglas; Stampas, Argyrios; Pascual-Leone, Alvaro; Cortes, Mar

2015-04-01

To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). Single-blind, randomized, sham-controlled, crossover study. Medical research institute and rehabilitation hospital. Volunteers (N = 9) with chronic SCI and motor dysfunction in wrist extensor muscles. Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis [ECR] muscle representation on the left primary motor cortex, cathode over the right supraorbital area) using 1 mA, 2 mA, or sham stimulation, delivered at rest, with at least 1 week between sessions. Corticospinal excitability was assessed with motor-evoked potentials (MEPs) from the ECR muscle using surface electromyography after transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold, and muscle strength were also investigated. Mean MEP amplitude significantly increased by approximately 40% immediately after 2mA a-tDCS (pre: 0.36 ± 0.1 mV; post: 0.47 ± 0.11 mV; P = .001), but not with 1 mA or sham. Maximal voluntary contraction measures remained unaltered across all conditions. Sensory threshold significantly decreased over time after 1mA (P = .002) and 2mA (P = .039) a-tDCS and did not change with sham. F-wave persistence showed a nonsignificant trend for increase (pre: 32% ± 12%; post: 41% ± 10%; follow-up: 46% ± 12%) after 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. The a-tDCS can transiently raise corticospinal excitability to affected muscles in patients with chronic SCI after 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in patients with SCI and highlights the importance of stimulation intensity. Copyright © 2015 American Congress of Rehabilitation

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

International Nuclear Information System (INIS)

Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

1981-01-01

The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

Science.gov (United States)

Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

2017-04-01

Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

The Underlying Mechanism of Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear Implant Users Assessed With Objective Measure.

Science.gov (United States)

Bahmer, Andreas; Baumann, Uwe

2016-10-01

Triphasic pulse stimulation prevents from facial nerve stimulation (FNS) because of a different electromyographic input-output function compared with biphasic pulse stimulation. FNS is sometimes observed in cochlear implant users as an unwanted side effect of electrical stimulation of the auditory nerve. The common stimulation applied in current cochlear implant consists of biphasic pulse patterns. Two common clinical remedies to prevent unpleasant FNS caused by activation of certain electrodes are to expand their pulse phase duration or simply deactivate them. Unfortunately, in some patients these methods do not provide sufficient FNS prevention. In these patients triphasic pulse can prevent from FNS. The underlying mechanism is yet unclear. Electromyographic (EMG) recordings of muscles innervated by the facial nerve (musculi orbicularis ori and oculi) were applied to quantitatively assess the effects on FNS. Triphasic and biphasic fitting maps were compared in four subjects with severe FNS. Based on the recordings, a model is presented which intends to explain the beneficial effects of triphasic pulse application. Triphasic stimulation provided by fitting of an OPUS 2 speech processor device. For three patients, EMG was successfully recorded depending on stimulation level up to uncomfortable and intolerable FNS stimulation as upper boarder. The obtained EMG recordings demonstrated high individual variability. However, a difference between the input-output function for biphasic and triphasic pulse stimulation was visually observable. Compared with standard biphasic stimulation, triphasic pulses require higher stimulation levels to elicit an equal amount of FNS, as reflected by EMG amplitudes. In addition, we assume a steeper slope of the input-output function for biphasic pulse stimulation compared with triphasic pulse stimulation. Triphasic pulse stimulation prevents from FNS because of a smaller gradient of EMG input-output function compared with biphasic pulse

Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

Science.gov (United States)

Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

2013-05-14

Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease.

Science.gov (United States)

Dafsari, Haidar Salimi; Weiß, Luisa; Silverdale, Monty; Rizos, Alexandra; Reddy, Prashanth; Ashkan, Keyoumars; Evans, Julian; Reker, Paul; Petry-Schmelzer, Jan Niklas; Samuel, Michael; Visser-Vandewalle, Veerle; Antonini, Angelo; Martinez-Martin, Pablo; Ray-Chaudhuri, K; Timmermann, Lars

2018-02-24

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome. We hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome. In this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and -activities of daily living, levodopa equivalent daily dose. We dichotomized patients into "QoL responders"/"non-responders" and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned "responders/non-responders" as dependent variable. All outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as "QoL non-responders". Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome. Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS. Copyright © 2018. Published by Elsevier

[Caffeine dependence].

Science.gov (United States)

Ogawa, Naoshi; Ueki, Hirofumi

2010-08-01

Caffeine is the most widely consumed psychoactive substance in the world and is a legal stimulant that is readily available to children. The potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Although in recent studies, a subset of the general population was found to demonstrate caffeine dependence. It is valuable for psychiatrists and primary care physicians to recognize caffeine dependence as a clinical syndrome, since some people are distressed by their caffeine use and feel they can not control or stop their problematic use.

Temperature-dependent changes in the viscoelasticity of intact resting mammalian (rat) fast- and slow-twitch muscle fibres.

Science.gov (United States)

Mutungi, G; Ranatunga, K W

1998-04-01

1. The tension and sarcomere length responses induced by ramp stretches (at amplitudes of 1-3 % fibre length (Lo) and speeds of 0.01-12 Lo s-1) were examined at different temperatures (range, 10-35 degrees C) in resting intact muscle fibre bundles isolated from the soleus (a slow-twitch muscle) and extensor digitorum longus (a fast-twitch muscle) of the rat. Some observations are also presented on the effects of chemical skinning on passive viscoelasticity at 10 degrees C. 2. As previously reported, the tension response to a ramp stretch, in different preparations and under various conditions, could be resolved into a viscous (P1), a viscoelastic (P2) and an elastic (P3) component and showed characteristic differences between slow and fast muscle fibres. 3. Chemical skinning of the muscle fibres led to a decrease in the amplitude of all three tension components. However, the fast-slow fibre differences remained after skinning. For example, the viscosity coefficient derived from P1 tension data decreased from 0.84 +/- 0.06 before skinning to 0.44 +/- 0.06 kN s m-2 after skinning in fast fibres; the corresponding values in slow fibres were 2.1 +/- 0.08 and 0.87 +/- 0.09 kN s m-2, respectively. 4. Increasing the experimental temperature from 10 to 35 degrees C led to a decrease in all the tension components in both fast and slow muscle fibre bundles. The decrease of P1 (viscous) tension was such that the viscosity coefficient calculated using P1 data was reduced from 0.84 +/- 0.1 to 0.43 +/- 0.05 kN s m-2 in fast fibres and from 2.0 +/- 0.1 to 1.0 +/- 0.1 kN s m-2 in slow fibres (Q10 of approximately 1.3 in both). 5. In both fast and slow muscle fibre preparations, the plateau tension of the viscoelastic component (P2) decreased by 60-80 % as the temperature was increased from 10 to 35 degrees C giving P2 tension a Q10 of approximately 1.4 in slow fibres and approximately 1.7 in the fast fibres. Additionally, the relaxation time of the viscoelasticity decreased from

Reactivity changes in hybrid thermal-fast reactor systems during fast core flooding

International Nuclear Information System (INIS)

Pesic, M.

1994-09-01

A new space-dependent kinetic model in adiabatic approximation with local feedback reactivity parameters for reactivity determination in the coupled systems is proposed in this thesis. It is applied in the accident calculation of the 'HERBE' fast-thermal reactor system and compared to usual point kinetics model with core-averaged parameters. Advantages of the new model - more realistic picture of the reactor kinetics and dynamics during local large reactivity perturbation, under the same heat transfer conditions, are underlined. Calculated reactivity parameters of the new model are verified in the experiments performed at the 'HERBE' coupled core. The model has shown that the 'HERBE' safety system can shutdown reactor safely and fast even in the case of highly set power trip and even under conditions of big partial failure of the reactor safety system (author)

Testosterone Suppression of CRH-stimulated Cortisol in Men

OpenAIRE

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

2005-01-01

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in ten men (ages 18–45) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower ...

Biophysical Model of Cortical Network Activity and the Influence of Electrical Stimulation

Science.gov (United States)

2015-11-13

model, multicompartment model, subdural cortical stimulation, anode, cathode, epilepsy REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S...and axon orientation in respect to the electrode position. 4) A single stimulation pulse causes a sequence of action potentials ectopically generated...Bergey, P.J. Franaszczuk. Phase-dependent stimulation effects on bursting activity in a neural network cortical simulation, Epilepsy Research (07 2008

FURNACE-J, 2-D Diffusion Burnup for Fast Reactors from JAERI Fast-Set

International Nuclear Information System (INIS)

Ikawa, Koji

1984-01-01

1 - Nature of physical problem solved: FURNACEJ is a two-dimensional diffusion-burnup code for use in the detailed burnup analysis of fast reactors. The code is an extension code of the FURNACE. There exists no essential difference between FURNACE and FURNACEJ. However, the latter can deal with JAERI-Fast-Set as its cross section library, while the former is designed to use ABBN set. Additionally, in FURNACEJ, group-dependent and -independent transverse buckling of each region can be computed and punched on cards, if desired. This is prepared for users so as to use them as input data for detailed two-dimensional x-y calculations. 2 - Restrictions on the complexity of the problem: Only r-z geometry is available

Fasting: a major limitation for resistance exercise training effects in rodents

Directory of Open Access Journals (Sweden)

W. das Neves

2017-11-01

Full Text Available Protocols that mimic resistance exercise training (RET in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1 untrained control rats, 2 untrained rats submitted to fasting periods, and 3 rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks, the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks. After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all. Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01. Altogether, these data indicate that fasting is a major limitation for RET in rats.

Characterisation of blue-light stimulated luminescence components in different quartz samples: Implications for dose measurement

DEFF Research Database (Denmark)

Jain, M.; Murray, A.S.; Bøtter-Jensen, L.

2003-01-01

-aliquot dose-evaluation protocols seem to be relatively free of complications when applied to quartz dominated by the fast OSL component coming from 325degreesC TL region, but this may not be true for quartz in which other components are more significant. An adequate understanding of how different OSL...... results from measurement of (a) sensitisation, (b) thermal stability, (c) recuperation, and (d) infrared response as a function of stimulation temperature from 3 different samples of sedimentary quartz selected on the basis of relative OSL contribution from different blue light stimulated linearly...

Fasting: a major limitation for resistance exercise training effects in rodents.

Science.gov (United States)

das Neves, W; de Oliveira, L F; da Silva, R P; Alves, C R R; Lancha, A H

2017-11-17

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (Pfasting is a major limitation for RET in rats.

Age-dependent effects of brain stimulation on network centrality

DEFF Research Database (Denmark)

Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus

2018-01-01

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task......-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age associated differential neural tDCS effects. Three “online” tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30...... characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing...

Advanced Safeguards Approaches for New Fast Reactors

International Nuclear Information System (INIS)

Durst, Philip C.; Therios, Ike; Bean, Robert; Dougan, A.; Boyer, Brian; Wallace, Rick L.; Ehinger, Michael H.; Kovacic, Don N.; Tolk, K.

2007-01-01

This third report in the series reviews possible safeguards approaches for new fast reactors in general, and the ABR in particular. Fast-neutron spectrum reactors have been used since the early 1960s on an experimental and developmental level, generally with fertile blanket fuels to 'breed' nuclear fuel such as plutonium. Whether the reactor is designed to breed plutonium, or transmute and 'burn' actinides depends mainly on the design of the reactor neutron reflector and the whether the blanket fuel is 'fertile' or suitable for transmutation. However, the safeguards issues are very similar, since they pertain mainly to the receipt, shipment and storage of fresh and spent plutonium and actinide-bearing 'TRU'-fuel. For these reasons, the design of existing fast reactors and details concerning how they have been safeguarded were studied in developing advanced safeguards approaches for the new fast reactors. In this regard, the design of the Experimental Breeder Reactor-II 'EBR-II' at the Idaho National Laboratory (INL) was of interest, because it was designed as a collocated fast reactor with a pyrometallurgical reprocessing and fuel fabrication line--a design option being considered for the ABR. Similarly, the design of the Fast Flux Facility (FFTF) on the Hanford Site was studied, because it was a successful prototype fast reactor that ran for two decades to evaluate fuels and the design for commercial-scale fast reactors

Reasons for betel quid chewing amongst dependent and non-dependent betel quid chewing adolescents: a school-based cross-sectional survey.

Science.gov (United States)

Hussain, Azmina; Zaheer, Sidra; Shafique, Kashif

2018-05-09

Betel quid (BQ) chewing in children is initiated in their adolescence. It is pivotal to understand adolescents' reasons behind chewing BQ. In this study, we aimed to evaluate the reasons for BQ chewing amongst adolescents using reasons for betel quid chewing scale (RBCS) and their associated dependency on it. This is a cross-sectional school based survey. Out of 2200 adolescents from 26 schools of Karachi, 874 BQ chewers were assessed for their reasons of BQ chewing and dependency on it. Regression analyses were employed to report crude and adjusted (after adjusting for all reasons of BQ chewing) effect sizes with 95% confidence interval and P-value was set significant at < 0.05. Students who believed that BQ chewing relaxes them (stimulation construct) were twice as likely to be dependent on BQ (OR = 2.36, 95% CI (1.20-4.65) as compared with others. Participants who thought it eases their decision making (stimulation construct), were sizably more likely to be dependent on BQ (OR = 9.65, 95% CI (4.15-22.43) than those who did not consider ease in decision making important. Adolescents who considered not chewing as rude (social/cultural construct), were thrice more likely to be dependent on BQ (OR = 2.50, 95% CI (1.11-5.63) than others. Stimulation remained fundamental chewing reason followed by social/cultural trigger amongst adolescents. Any future intervention may get favorable results if it addresses ways to overcome stimulation and social/cultural barriers that are strongly associated with BQ chewing and dependency.

Decision-making style, nicotine and caffeine use and dependence.

Science.gov (United States)

Phillips, James G; Ogeil, Rowan P

2015-11-01

As therapeutic interventions are being developed utilising telehealth and mobile phones, it is important to understand how substance-dependent individuals will respond to offers of online assistance. The present paper considered the following: (1) how decision-making style is associated with use and dependence upon commonly used stimulants and (2) how it influences behavioural responses to electronic offers of further information about these drugs. An online survey examined patterns of nicotine and caffeine use, administered Severity of Dependence Scales for caffeine and nicotine and assessed decision-making style using the Melbourne Decision Making Questionnaire and mood using the Kessler Distress Scale. Upon completing these scales, the 181 participants with a mean age of 28.14 years were offered further information online. Stimulant dependence was associated with psychological distress. Caffeine dependence was linked to hypervigilance (panic). Decisional self-esteem varied with stimulant dependence and Kessler Distress Scale score. Participants with high decisional self-esteem declined electronic offers of further information. Confidence rather than defensive avoidance was a factor in reducing information-seeking behaviours on the Internet. Copyright © 2015 John Wiley & Sons, Ltd.

Quantitative EEG findings associated with chronic stimulant and cannabis abuse and ADHD in an adult male substance use disorder population.

Science.gov (United States)

Trudeau, D L; Thuras, P; Stockley, H

1999-10-01

QEEG was studied in a population of chronic male PSUD/ADHD (psychoactive substance use disorder/attention deficit hyperactivity disorder) subjects vs. a matched sample of non-ADHD subjects with PSUD. Our first interest in conducting this study was to determine if the Thatcher University of Maryland database and complex demodulation method could replicate the specific QEEG findings reported for cocaine and cannabis using the John-NYU database and Fourier Transform method. The effects of cannabis and stimulants were also studied both separately and together to see if there were interactions and to see if the QEEG changes associated with chronic stimulant dependence were predicted by childhood ADHD status. Eyes-closed QEEGs were obtained and two independent artifacted 60 second samples were compared for reliability. The Thatcher database was used to analyze QEEG data from 56 subjects with mixed substance use disorder. Results showed that the Thatcher database replicates the John database for chronic stimulant dependence findings. Because of confounding variables of alcohol and polysubstance abuse, the findings related to cannabis and stimulant interaction were difficult to assess. Cannabis and stimulant dependence together produced more QEEG changes than either alone. More right temporal abnormalities were observed with stimulant dependence. In the absence of stimulant use, the QEEG effects of cannabis were relatively small; however, sample selection and methods used precluded comparison to previous studies. The persistent QEEG abnormalities associated with chronic stimulant dependence were independent of ADHD status in this sample using the methods of this study. Further research is needed to clarify the relationship of stimulant dependence with QEEG changes and ADHD status, and to clarify the interactions of chronic stimulant and cannabis abuse on QEEG.

Calmodulin stimulation of calcium transport in carrot microsomal vesicles

International Nuclear Information System (INIS)

Pierce, W.S.; Sze, H.

1987-01-01

ATP-dependent 45 Ca 2+ uptake into microsomal vesicles isolated from cultured carrot cells (Daucus carota Danvers) was stimulated 2-3 fold by 5 ug/ml calmodulin (CaM). Microsomal vesicles separated with a linear sucrose gradient showed two peaks with CaM-stimulated Ca 2+ uptake activities. One peak (at 1.12 g/cc) comigrated with the activity of the antimycin A-insensitive NADH-dependent cytochrome c reductase. This transport activity was enhanced 10-20 fold by 10 mM oxalate and appeared to be associates with vesicles derived primarily from the ER. The other peak of CaM-stimulated Ca 2+ uptake (at 1.17 g/cc) was not affected by oxalate. These vesicles are probably derived from the plasma membrane. Preliminary experiments with the low-density vesicles (ER) vesicles, indicate that inositol-1,4,5-trisphosphate caused a transient reduction in intravesicular Ca 2+ . These results are consistent with the ER being an important site of intracellular Ca 2+ regulation

Ultra-fast ipsilateral DPOAE adaptation not modulated by attention?

Science.gov (United States)

Dalhoff, Ernst; Zelle, Dennis; Gummer, Anthony W.

2018-05-01

Efferent stimulation of outer hair cells is supposed to attenuate cochlear amplification of sound waves and is accompanied by reduced DPOAE amplitudes. Recently, a method using two subsequent f2 pulses during presentation of a longer f1 pulse was introduced to measure fast ipsilateral adaptation effects on separated DPOAE components. Compensating primary-tone onsets for their latencies at the f2-tonotopic place, the average adaptation measured in four normal-hearing subjects was 5.0 dB with a time constant below 5 ms. In the present study, two experiments were performed to determine the origin of this ultra-fast ipsilateral adaptation effect. The first experiment measured ultra-fast ipsilateral adaptation using a two-pulse paradigm at three frequencies in the four subjects, while controlling for visual attention of the subjects. The other experiment also controlled for visual attention, but utilized a sequence of f2 short pulses in the presence of a continuous f1 tone to sample ipsilateral adaptation effects with longer time constants in eight subjects. In the first experiment, no significant change in the ultra-fast adaptation between non-directed attention and visual attention could be detected. In contrast, the second experiment revealed significant changes in the magnitude of the slower ipsilateral adaptation in the visual-attention condition. In conclusion, the lack of an attentional influence indicates that the ultra-fast ipsilateral DPOAE adaptation is not solely mediated by the medial olivocochlear reflex.

Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

DEFF Research Database (Denmark)

Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

2008-01-01

The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

One-trial overshadowing: Evidence for fast specific fear learning in humans.

Science.gov (United States)

Haesen, Kim; Beckers, Tom; Baeyens, Frank; Vervliet, Bram

2017-03-01

Adaptive defensive actions necessitate a fear learning system that is both fast and specific. Fast learning serves to minimize the number of threat confrontations, while specific learning ensures that the acquired fears are tied to threat-relevant cues only. In Pavlovian fear conditioning, fear acquisition is typically studied via repetitive pairings of a single cue with an aversive experience, which is not optimal for the examination of fast specific fear learning. In this study, we adopted the one-trial overshadowing procedure from basic learning research, in which a combination of two visual cues is presented once and paired with an aversive electrical stimulation. Using on-line shock expectancy ratings, skin conductance reactivity and startle reflex modulation as indices of fear learning, we found evidence of strong fear after a single conditioning trial (fast learning) as well as attenuated fear responding when only half of the trained stimulus combination was presented (specific learning). Moreover, specificity of fear responding tended to correlate with levels of state and trait anxiety. These results suggest that one-trial overshadowing can be used as a model to study fast specific fear learning in humans and individual differences therein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurements of fast neutron spectra in iron, uranium and sodium-iron assemblies

International Nuclear Information System (INIS)

Kappler, F.; Pieroni, N.; Rusch, D.; Schmidt, A.; Wattecamps, E.; Werle, H.

1979-01-01

Spectrum measurements were performed at the fast subcritical facility SUAK to test nuclear data and computer codes used in fast reactor calculations. In order to obtain a specific and quantitative interpretation of discrepancies between measured and calculated spectrum, homogeneous assemblies consisting of single materials were investigated. The leakage spectrum of iron and uranium cylinders was measured by time-of-flight and proportional counters. Time-dependent leakage spectra were measured by a NE 213 liquid scintillator. It was demonstrated that the investigation of time-dependent spectra is a sensitive test of inelastic scattering cross section data. The effect of an interface on fast neutron spectra was also investigated by measuring space dependent spectra across a sodium-iron interface. The measured spectra of these assemblies are suitable for testing the adequacy of computational approximations and cross section data. (author)

Efficacy of Carcass Electrical Stimulation in Meat Quality Enhancement: A Review

Science.gov (United States)

Adeyemi, Kazeem Dauda; Sazili, Awis Qurni

2014-01-01

The use of electrical stimulation (ES) as a management tool to improve meat quality and efficiency of meat processing is reviewed. The basis of the efficacy of ES is its ability to fast track postmortem glycolysis, which in turn stimulates myriad histological, physical, biochemical, biophysical and physiological changes in the postmortem muscle. Electrical stimulation hastens the onset and resolution of rigor mortis thereby reducing processing time and labor and plays a vital role in improving meat tenderness and other meat quality traits. However, ES may have negative impacts on some meat quality traits such as color stability and water holding capacity in some animals. Electrical stimulation is not an end in itself. In order to achieve the desired benefits from its application, the technique must be properly used in conjunction with various intricate antemortem, perimortem and postmortem management practices. Despite extensive research on ES, the fundamental mechanisms and the appropriate commercial applications remained obscured. In addition, muscles differ in their response to ES. Thus, elementary knowledge of the various alterations with respect to muscle type is needed in order to optimize the effectiveness of ES in the improvement of meat quality. PMID:25049973

Efficacy of Carcass Electrical Stimulation in Meat Quality Enhancement: A Review

Directory of Open Access Journals (Sweden)

Kazeem Dauda Adeyemi

2014-03-01

Full Text Available The use of electrical stimulation (ES as a management tool to improve meat quality and efficiency of meat processing is reviewed. The basis of the efficacy of ES is its ability to fast track postmortem glycolysis, which in turn stimulates myriad histological, physical, biochemical, biophysical and physiological changes in the postmortem muscle. Electrical stimulation hastens the onset and resolution of rigor mortis thereby reducing processing time and labor and plays a vital role in improving meat tenderness and other meat quality traits. However, ES may have negative impacts on some meat quality traits such as color stability and water holding capacity in some animals. Electrical stimulation is not an end in itself. In order to achieve the desired benefits from its application, the technique must be properly used in conjunction with various intricate antemortem, perimortem and postmortem management practices. Despite extensive research on ES, the fundamental mechanisms and the appropriate commercial applications remained obscured. In addition, muscles differ in their response to ES. Thus, elementary knowledge of the various alterations with respect to muscle type is needed in order to optimize the effectiveness of ES in the improvement of meat quality.

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

Science.gov (United States)

Oikawa, S; Oetzel, G R

2006-08-01

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

Science.gov (United States)

Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

2014-12-01

Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

Directory of Open Access Journals (Sweden)

Suzumiya Junji

2011-07-01

Full Text Available Abstract Background Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP production by adjacent stromal cells. Its first Ig domain (ECI contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active. Methods The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production. Results ECI carrying a chitobiose unit, ECI-(GlcNAc 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man3(GlcNAc2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc2. Conclusions Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.

Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.

Science.gov (United States)

Colzato, Lorenza S; Ritter, Simone M; Steenbergen, Laura

2018-03-01

Creativity is one of the most important cognitive skills in our complex and fast-changing world. Previous correlative evidence showed that gamma-aminobutyric acid (GABA) is involved in divergent but not convergent thinking. In the current study, a placebo/sham-controlled, randomized between-group design was used to test a causal relation between vagus nerve and creativity. We employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique to stimulate afferent fibers of the vagus nerve and speculated to increase GABA levels, in 80 healthy young volunteers. Creative performance was assessed in terms of divergent thinking (Alternate Uses Task) and convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task, Idea Selection Task). Results demonstrate active tVNS, compared to sham stimulation, enhanced divergent thinking. Bayesian analysis reported the data to be inconclusive regarding a possible effect of tVNS on convergent thinking. Therefore, our findings corroborate the idea that the vagus nerve is causally involved in creative performance. Even thought we did not directly measure GABA levels, our results suggest that GABA (likely to be increased in active tVNS condition) supports the ability to select among competing options in high selection demand (divergent thinking) but not in low selection demand (convergent thinking). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rectal motility after sacral nerve stimulation for faecal incontinence

DEFF Research Database (Denmark)

Michelsen, H B; Worsøe, J; Krogh, K

2010-01-01

Sacral nerve stimulation (SNS) is effective against faecal incontinence, but the mode of action is obscure. The aim of this study was to describe the effects of SNS on fasting and postprandial rectal motility. Sixteen patients, 14 women age 33-73 (mean 58), with faecal incontinence of various...... contractions, total time with cyclic rectal contractions, the number of aborally and orally propagating contractions, the number of anal sampling reflexes or rectal wall tension during contractions. Postprandial changes in rectal tone were significantly reduced during SNS (P

Effects of in vitro hypoxia on depolarization-stimulated accumulation of inositol phosphates in synaptosomes

International Nuclear Information System (INIS)

Huang, H.M.; Gibson, G.E.

1989-01-01

The effects of potassium and in vitro histotoxic hypoxia on phosphatidylinositol turnover in rat cortical synaptosomes were determined. [2- 3 H] Inositol prelabelled rat synaptosomes were prepared from cerebral cortex slices that had been incubated with [2- 3 H] inositol. Depolarization with 60 mM KCl increased [2- 3 H] inositol phosphates in a time dependent manner. Depolarization with 60 mM KCl increased [2- 3 H]inositol trisphosphate transiently at 5 s. K + induced rapid formation of [2- 3 H] inositol monophosphate with time. One minute of hypoxia enhance sium-stimulate [2 3 H]inositol bisphosphate and maintained an elevated level for at least 5 min. K + stimulated gradual formation of [2- 3 H] inositol monophosphate with time. One minute of hypoxia enhanced potassium-stimulated [2- 3 H] inositol bisphosphate formation. However, 30 min of hypoxia impaired potassium-stimulated accumulation of [2- 3 H]inositol phosphates. The effects of histotoxic hypoxia were all dependent upon calcium in the medium and on K + -depolarization. Thus, hypoxia altered the K + induced accumulation of inositol phosphates in prelabelled synaptosomes in a time dependent, biphasic manner that was calcium dependent

A fast simulation tool for evaluation of novel well stimulation techniques for tight gas reservoirs

NARCIS (Netherlands)

Egberts, P.J.P.; Peters, E.

2015-01-01

For stimulation of tight fields, alternatives to hydraulic fracturing based on hydraulic jetting are becoming available. With hydraulic jetting many (10 to 20) laterals can be created in a (sub-) vertical well. The laterals are 100 to 200 m long, typically 4 laterals are applied with a small

Luminescence lifetimes in quartz: dependence on annealing temperature prior to beta irradiation

International Nuclear Information System (INIS)

Galloway, R.B.

2002-01-01

It is well known that the thermal history of a quartz sample influences the optically stimulated luminescence sensitivity of the quartz. It is found that the optically stimulated luminescence lifetime, determined from time resolved spectra obtained with pulsed stimulation, also depends on past thermal treatment. For samples at 20 deg. C during stimulation, the lifetime depends on beta dose and on duration of preheating at 220 deg. C prior to stimulation for quartz annealed at 600 deg. C and above, but is independent of these factors for quartz annealed at 500 deg. C and below. For stimulation at higher temperatures, the lifetime becomes shorter if the sample is held at temperatures above 125 deg. C during stimulation, in a manner consistent with thermal quenching. A single exponential decay is all that is required to fit the time resolved spectra for un-annealed quartz regardless of the temperature during stimulation (20-175 deg. C), or to fit the time resolved spectra from all samples held at 20 deg. C during stimulation, regardless of annealing temperature (20-1000 deg. C). An additional shorter lifetime is found for some combinations of annealing temperature and temperature during stimulation. The results are discussed in terms of a model previously used to explain thermal sensitisation. The luminescence lifetime data are best explained by the presence of two principal luminescence centres, their relative importance depending on the annealing temperature, with a third centre involved for limited combinations of annealing temperature and temperature during stimulation

Impact of Fast Charging on Life of EV Batteries

Energy Technology Data Exchange (ETDEWEB)

Neubauer, Jeremy; Wood, Eric; Burton, Evan; Smith, Kandler; Pesaran, Ahmad A.

2015-05-03

Utilization of public charging infrastructure is heavily dependent on user-specific travel behavior. The availability of fast chargers can positively affect the utility of battery electric vehicles, even given infrequent use. Estimated utilization rates do not appear frequent enough to significantly impact battery life. Battery thermal management systems are critical in mitigating dangerous thermal conditions on long distance tours with multiple fast charge events.

Prolonged fasting activates Nrf2 in post-weaned elephant seals.

Science.gov (United States)

Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

Advanced Safeguards Approaches for New Fast Reactors

Energy Technology Data Exchange (ETDEWEB)

Durst, Philip C.; Therios, Ike; Bean, Robert; Dougan, A.; Boyer, Brian; Wallace, Rick L.; Ehinger, Michael H.; Kovacic, Don N.; Tolk, K.

2007-12-15

This third report in the series reviews possible safeguards approaches for new fast reactors in general, and the ABR in particular. Fast-neutron spectrum reactors have been used since the early 1960s on an experimental and developmental level, generally with fertile blanket fuels to “breed” nuclear fuel such as plutonium. Whether the reactor is designed to breed plutonium, or transmute and “burn” actinides depends mainly on the design of the reactor neutron reflector and the whether the blanket fuel is “fertile” or suitable for transmutation. However, the safeguards issues are very similar, since they pertain mainly to the receipt, shipment and storage of fresh and spent plutonium and actinide-bearing “TRU”-fuel. For these reasons, the design of existing fast reactors and details concerning how they have been safeguarded were studied in developing advanced safeguards approaches for the new fast reactors. In this regard, the design of the Experimental Breeder Reactor-II “EBR-II” at the Idaho National Laboratory (INL) was of interest, because it was designed as a collocated fast reactor with a pyrometallurgical reprocessing and fuel fabrication line – a design option being considered for the ABR. Similarly, the design of the Fast Flux Facility (FFTF) on the Hanford Site was studied, because it was a successful prototype fast reactor that ran for two decades to evaluate fuels and the design for commercial-scale fast reactors.

Fast and accurate computation of projected two-point functions

Science.gov (United States)

Grasshorn Gebhardt, Henry S.; Jeong, Donghui

2018-01-01

We present the two-point function from the fast and accurate spherical Bessel transformation (2-FAST) algorithm1Our code is available at https://github.com/hsgg/twoFAST. for a fast and accurate computation of integrals involving one or two spherical Bessel functions. These types of integrals occur when projecting the galaxy power spectrum P (k ) onto the configuration space, ξℓν(r ), or spherical harmonic space, Cℓ(χ ,χ'). First, we employ the FFTLog transformation of the power spectrum to divide the calculation into P (k )-dependent coefficients and P (k )-independent integrations of basis functions multiplied by spherical Bessel functions. We find analytical expressions for the latter integrals in terms of special functions, for which recursion provides a fast and accurate evaluation. The algorithm, therefore, circumvents direct integration of highly oscillating spherical Bessel functions.

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

Science.gov (United States)

Kolodziej, Angela; Lippert, Michael; Angenstein, Frank; Neubert, Jenni; Pethe, Annette; Grosser, Oliver S; Amthauer, Holger; Schroeder, Ulrich H; Reymann, Klaus G; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

2014-12-01

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography. Copyright © 2014 The Authors

Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

Science.gov (United States)

Ducrot, Charles; Fortier, Emmanuel; Bouchard, Claude; Rompré, Pierre-Paul

2013-01-01

Previous studies have shown that blockade of ventral tegmental area (VTA) glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VTA neurons, a fast and short lasting depolarization mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VTA neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VTA neuronal activity, we studied the effects of VTA AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for 2 h after bilateral VTA microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5 μl/side) and of a single dose (0.825 nmol/0.5 μl/side) of the NMDA antagonist, PPPA (2R,4S)-4-(3-Phosphonopropyl)-2-piperidinecarboxylic acid). NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VTA sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected, respectively, into the anterior and posterior VTA. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VTA neurons, to

Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

Directory of Open Access Journals (Sweden)

Charles eDucrot

2013-10-01

Full Text Available Previous studies have shown that blockade of ventral midbrain (VM glutamate N-Methyl-D-Aspartate (NMDA receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VM neurons, a fast and short lasting depolarisation mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VM neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VM neuronal activity, we studied the effects of VM AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for two hours after bilateral VM microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(fquinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5ul/side and of a single dose (0.825 nmol/0.5ul/side of the NMDA antagonist, PPPA (2R,4S-4-(3-Phosphonopropyl-2-piperidinecarboxylic acid. NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VM sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected respectively into the anterior and posterior VM. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VM neurons, to modulate

Extending food deprivation reverses the short-term lipolytic response to fasting: role of the triacylglycerol/fatty acid cycle.

Science.gov (United States)

Weber, Jean-Michel; Reidy, Shannon P

2012-05-01

The effects of short-term food deprivation on lipid metabolism are well documented, but little is known about prolonged fasting. This study monitored the kinetics of glycerol (rate of appearance, R(a) glycerol) and non-esterified fatty acids (R(a) NEFA) in fasting rabbits. Our goals were to determine whether lipolysis is stimulated beyond values seen for short-term fasting, and to characterize the roles of primary (intracellular) and secondary (with transit through the circulation) triacylglycerol/fatty acid cycling (TAG/FA cycling) in regulating fatty acid allocation to oxidation or re-esterification. R(a) glycerol (9.62±0.72 to 15.29±0.96 μmol kg(-1) min(-1)) and R(a) NEFA (18.05±2.55 to 31.25±1.93 μmol kg(-1) min(-1)) were stimulated during the first 2 days of fasting, but returned to baseline after 4 days. An initial increase in TAG/FA cycling was followed by a reduction below baseline after 6 days without food, with primary and secondary cycling contributing to these responses. We conclude that the classic activation of lipolysis caused by short-term fasting is abolished when food deprivation is prolonged. High rates of re-esterification may become impossible to sustain, and TAG/FA cycling could decrease to reduce its cost to 3% of total energy expenditure. Throughout prolonged fasting, fatty acid metabolism gradually shifts towards increased oxidation and reduced re-esterification. Survival is achieved by pressing fuel selection towards the fatty acid dominance of energy metabolism and by slowing substrate cycles to assist metabolic suppression. However, TAG/FA cycling remains active even after prolonged fasting, suggesting that re-esterification is a crucial mechanism that cannot be stopped without harmful consequences.

A Muscle’s Force Depends on the Recruitment Patterns of Its Fibers

Science.gov (United States)

Wakeling, James M.; Lee, Sabrina S. M.; Arnold, Allison S.; de Boef Miara, Maria; Biewener, Andrew A.

2012-01-01

Biomechanical models of whole muscles commonly used in simulations of musculoskeletal function and movement typically assume that the muscle generates force as a scaled-up muscle fiber. However, muscles are comprised of motor units that have different intrinsic properties and that can be activated at different times. This study tested whether a muscle model comprised of motor units that could be independently activated resulted in more accurate predictions of force than traditional Hill-type models. Forces predicted by the models were evaluated by direct comparison with the muscle forces measured in situ from the gastrocnemii in goats. The muscle was stimulated tetanically at a range of frequencies, muscle fiber strains were measured using sonomicrometry, and the activation patterns of the different types of motor unit were calculated from electromyographic recordings. Activation patterns were input into five different muscle models. Four models were traditional Hill-type models with different intrinsic speeds and fiber-type properties. The fifth model incorporated differential groups of fast and slow motor units. For all goats, muscles and stimulation frequencies the differential model resulted in the best predictions of muscle force. The in situ muscle output was shown to depend on the recruitment of different motor units within the muscle. PMID:22350666

Increased sensitivity of thyroid hormone-mediated signaling despite prolonged fasting.

Science.gov (United States)

Martinez, Bridget; Scheibner, Michael; Soñanez-Organis, José G; Jaques, John T; Crocker, Daniel E; Ortiz, Rudy M

2017-10-01

Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental study on stimulated scattering of ZnO nanospheres dispersed in water

Energy Technology Data Exchange (ETDEWEB)

Shi, Jiulin, E-mail: hyq1304@126.com; Wu, Haopeng [Nanchang Hangkong University, Jiangxi Engineering Laboratory for Optoelectronics Testing Technology (China); Yan, Feng; Yang, Junjie [Nanchang Hangkong University, School of Measuring and Optical Engineering (China); He, Xingdao, E-mail: xingdaohe@126.com [Nanchang Hangkong University, Jiangxi Engineering Laboratory for Optoelectronics Testing Technology (China)

2016-01-15

The backward stimulated scattering (BSS) from ZnO nanospheres dispersed in water has been investigated experimentally by employing a Nd:YAG pulse laser with ∼532 nm wavelength and ∼8 ns pulse width as the pump laser source. The present results show that the BSS effect is uniquely and unequivocally different compared to other known stimulated scattering, such as stimulated Rayleigh scattering, stimulated Brillouin scattering, and stimulated Raman scattering, and it displays the characteristics of no frequency shift and threshold dependence on initial spontaneous Mie scattering seed source. These can be understood by means of the Mie scattering theory and a laser-induced stationary Bragg grating model.

Potential of intestinal electrical stimulation for obesity: a preliminary canine study.

Science.gov (United States)

Yin, Jieyun; Ouyang, Hui; Chen, Jiande D Z

2007-05-01

The aims of this study were to investigate the therapeutic potential of intestinal electrical stimulation (IES) for obesity. Experiments were performed to investigate the effects of IES on food intake, gastric tone, gastric accommodation, and its possible pathway. Ten normal dogs and six dogs with truncal vagotomy were used in this study. Each dog was equipped with a gastric cannula for the measurement of gastric tone and accommodation by barostat and one pair of duodenal serosal electrodes for IES. The experiment on food intake was composed of both control session without IES and IES session after a 28-hour fast. The experiment on gastric tone and accommodation was performed in the fasting and fed states and composed of three sessions: control, IES, and IES with N(G)-nitro-l-arginine. IES significantly reduced food intake in the normal dogs (459.0 vs. 312.6 grams, p < 0.001). The food intake was negatively correlated with the fasting gastric volume during IES. IES significantly decreased fasting gastric tone in the normal dogs reflected as a decrease in gastric volume (89.1 vs. 261.3 mL, p < 0.01), which was abolished by vagotomy and N(G)-nitro-l-arginine. IES reduces food intake and inhibits gastric tone in the fasting state. The inhibitory effect of IES on gastric tone is mediated by both vagal and nitrergic pathway.

Induction of hyperandrogenism in lean reproductive-age women stimulates proatherogenic inflammation.

Science.gov (United States)

González, F; Sreekumaran Nair, K; Basal, E; Bearson, D M; Schimke, J M; Blair, H E

2015-06-01

We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion. © Georg Thieme Verlag KG Stuttgart · New York.

Application of reflective memory network in Tokamak fast controller

International Nuclear Information System (INIS)

Weng Chuqiao; Zhang Ming; Liu Rui; Zheng Wei; Zhuang Ge

2014-01-01

A specific application of reflective memory network in Tokamak fast controller was introduced in this paper. The PMC-5565 reflective memory card and ACC-5565 network hub were used to build a reflective memory real-time network to test its real- time function. The real-time, rapidity and determinacy of the time delay for fast controller controlling power device under the reflective memory network were tested in the LabVIEW RT real-time operation system. Depending on the reflective memory technology, the data in several fast controllers were synchronized, and multiple control tasks using a single control task were finished. The experiment results show that the reflective memory network can meet the real-time requirements for fast controller to perform the feedback control over devices. (authors)

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

Science.gov (United States)

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

2006-11-01

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Application of synthesis methods to two-dimensional fast reactor transient study

International Nuclear Information System (INIS)

Izutsu, Sadayuki; Hirakawa, Naohiro

1978-01-01

Space time synthesis and time synthesis codes were developed and applied to the space-dependent kinetics benchmark problem of a two-dimensional fast reactor model, and it was found both methods are accurate and economical for the fast reactor kinetics study. Comparison between the space time synthesis and the time synthesis was made. Also, in space time synthesis, the influence of the number of trial functions on the error and on the computing time and the effect of degeneration of expansion coefficients are investigated. The matrix factorization method is applied to the inversion of the matrix equation derived from the synthesis equation, and it is indicated that by the use of this scheme space-dependent kinetics problem of a fast reactor can be solved efficiently by space time synthesis. (auth.)

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts.

Science.gov (United States)

Dafsari, Haidar Salimi; Petry-Schmelzer, Jan Niklas; Ray-Chaudhuri, K; Ashkan, Keyoumars; Weis, Luca; Dembek, Till A; Samuel, Michael; Rizos, Alexandra; Silverdale, Monty; Barbe, Michael T; Fink, Gereon R; Evans, Julian; Martinez-Martin, Pablo; Antonini, Angelo; Visser-Vandewalle, Veerle; Timmermann, Lars

2018-03-16

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS. To investigate the impact of active contact location on NMS in STN-DBS in PD. In this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables. NMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores. Our study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes. Copyright © 2018. Published by Elsevier Inc.

Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

Directory of Open Access Journals (Sweden)

Fabrice Le Boeuf

2017-09-01

Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

Theory of feedback controlled brain stimulations for Parkinson's disease

Science.gov (United States)

Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

2016-01-01

Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

A calcium-dependent protein kinase can inhibit a calmodulin-stimulated Ca2+ pump (ACA2) located in the endoplasmic reticulum of Arabidopsis

Science.gov (United States)

Hwang, I.; Sze, H.; Harper, J. F.; Evans, M. L. (Principal Investigator)

2000-01-01

The magnitude and duration of a cytosolic Ca(2+) release can potentially be altered by changing the rate of Ca(2+) efflux. In plant cells, Ca(2+) efflux from the cytoplasm is mediated by H(+)/Ca(2+)-antiporters and two types of Ca(2+)-ATPases. ACA2 was recently identified as a calmodulin-regulated Ca(2+)-pump located in the endoplasmic reticulum. Here, we show that phosphorylation of its N-terminal regulatory domain by a Ca(2+)-dependent protein kinase (CDPK isoform CPK1), inhibits both basal activity ( approximately 10%) and calmodulin stimulation ( approximately 75%), as shown by Ca(2+)-transport assays with recombinant enzyme expressed in yeast. A CDPK phosphorylation site was mapped to Ser(45) near a calmodulin binding site, using a fusion protein containing the N-terminal domain as an in vitro substrate for a recombinant CPK1. In a full-length enzyme, an Ala substitution for Ser(45) (S45/A) completely blocked the observed CDPK inhibition of both basal and calmodulin-stimulated activities. An Asp substitution (S45/D) mimicked phosphoinhibition, indicating that a negative charge at this position is sufficient to account for phosphoinhibition. Interestingly, prior binding of calmodulin blocked phosphorylation. This suggests that, once ACA2 binds calmodulin, its activation state becomes resistant to phosphoinhibition. These results support the hypothesis that ACA2 activity is regulated as the balance between the initial kinetics of calmodulin stimulation and CDPK inhibition, providing an example in plants for a potential point of crosstalk between two different Ca(2+)-signaling pathways.

Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population

OpenAIRE

Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

2015-01-01

Background: Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Objectives: Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. Patients and Methods: The current study was a correlation study. We evaluated 285 male substance users and ...

Understanding the True Stimulated Reservoir Volume in Shale Reservoirs

KAUST Repository

Hussain, Maaruf; Saad, Bilal; Negara, Ardiansyah; Sun, Shuyu

2017-01-01

Successful exploitation of shale reservoirs largely depends on the effectiveness of hydraulic fracturing stimulation program. Favorable results have been attributed to intersection and reactivation of pre-existing fractures by hydraulically

Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

Science.gov (United States)

Kwon, Yong Hyun; Jang, Sung Ho

2012-01-01

We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation. PMID:25624815

Radiation dosimetry by optically stimulated phosphorescence of CaF2:Mn

International Nuclear Information System (INIS)

Bernhardt, R.

1974-01-01

In addition to the light emission which occurs in TL, trapped electrons in CaF 2 :Mn can also be released by stimulation with visible and UV light. The measurement of stimulated light emission is disturbed by illumination. But there is an optically-stimulated phosphorescence, which permits to separate measurement of stimulated light emission and illumination. A theory is given. During illumination a part of the released electrons are captured by flat traps, which are emptied at room temperature. A dose dependent signal can be measured at a defined time after the stimulating pulse of visible light. Dosimeters (CaF 2 :Mn teflon disks) were illuminated by the light of a tungsten lamp. The dose response curve was found to be linear from 1 to 10 5 rads. The response curve obtained for optical stimulation was similar to the TL-response curve. Fading of the optically-stimulated signal was higher than TL-fading. Repeated readings of a single sample are possible. The number of readings is dependent on illumination conditions. Accuracy of sample to sample was about 3.5% (standard deviation). There are two background signals. (1) Post-irradiation phosphorescence occurs. Flat traps are also filled after 60 Co gamma excitation. The measurement of the signal is possible after decay of post-irradiation phosphorescence. (2) There is an optically-excited phosphorescence, which also occurs if all trapped electrons are released. The lower limit of dose measurements is given by deviations of optically-excited emission and the dark-current of the photomultiplier tube. (author)

Subthalamic nucleus stimulation influences expression and suppression of impulsive behaviour in Parkinson’s disease

Science.gov (United States)

Ridderinkhof, K. Richard; Elias, William J.; Frysinger, Robert C.; Bashore, Theodore R.; Downs, Kara E.; van Wouwe, Nelleke C.; van den Wildenberg, Wery P. M.

2010-01-01

Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson’s disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson’s disease (n = 17) on performance in a Simon task. In this reaction time task, conflict between premature response impulses and goal-directed action selection is manipulated. We applied distributional analytic methods to separate the strength of the initial response impulse from the proficiency of inhibitory control engaged subsequently to suppress the impulse. Patients with Parkinson’s disease were tested when stimulation was either turned on or off. Mean conflict interference effects did not differ between controls and patients, or within patients when stimulation was on versus off. In contrast, distributional analyses revealed two dissociable effects of subthalamic nucleus stimulation. Fast response errors indicated that stimulation increased impulsive, premature responding in high conflict situations. Later in the reaction process, however, stimulation improved the proficiency with which inhibitory control was engaged to suppress these impulses selectively, thereby facilitating selection of the correct action. This temporal dissociation supports a conceptual framework for resolving past paradoxical findings and further highlights that dynamic aspects of impulse and inhibitory control underlying goal-directed behaviour rely in part on neural circuitry inclusive of the subthalamic nucleus. PMID:20861152

Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome.

Science.gov (United States)

Zangeneh, Farideh; Salman Yazdi, Reza; Naghizadeh, Mohammad Mehdi; Abedinia, Nasrin

2015-06-01

To determine the effects of Ramadan fasting on serum levels of stress neurohormones in Iranian women with polycystic ovary syndrome (PCOS). This study was a clinical trial and was performed during July 2011 (month of Ramadan) in Royan institute, Tehran. A total of 40 women who were aged 20-40 years and known cases of PCOS and had no other medical diseases were included in the study. They were divided into two groups as follows: (i) study group (n = 20) who participated in Ramadan fasting and (ii) control group (n = 20) who did not participate in fasting. For evaluating Ramadan's effect on the level of neurohormones serum level of the following variables were evaluated before and after Ramadan: cortisol, adrenaline (A), noradrenalin (NA), beta-endorphin (β-End), insulin, as well as sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. In the study group after Ramadan serum cortisol and nor-adrenaline levels were significantly lower than the initial levels obtained at beginning of Ramadan (p Ramadan fasting decreases stress neurohormones in women with PCOS.

Global perception depends on coherent work of bilateral visual cortices: transcranial magnetic stimulation (TMS) studies.

Science.gov (United States)

Zhang, Xin; Han, ShiHui

2007-08-01

Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchical stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the coherent work of bilateral visual cortices.

Why Do Irrelevant Alternatives Matter? An fMRI-TMS Study of Context-Dependent Preferences.

Science.gov (United States)

Chung, Hui-Kuan; Sjöström, Tomas; Lee, Hsin-Ju; Lu, Yi-Ta; Tsuo, Fu-Yun; Chen, Tzai-Shuen; Chang, Chi-Fu; Juan, Chi-Hung; Kuo, Wen-Jui; Huang, Chen-Ying

2017-11-29

Both humans and animals are known to exhibit a violation of rationality known as "decoy effect": introducing an irrelevant option (a decoy) can influence choices among other (relevant) options. Exactly how and why decoys trigger this effect is not known. It may be an example of fast heuristic decision-making, which is adaptive in natural environments, but may lead to biased choices in certain markets or experiments. We used fMRI and transcranial magnetic stimulation to investigate the neural underpinning of the decoy effect of both sexes. The left ventral striatum was more active when the chosen option dominated the decoy. This is consistent with the hypothesis that the presence of a decoy option influences the valuation of other options, making valuation context-dependent even when choices appear fully rational. Consistent with the idea that control is recruited to prevent heuristics from producing biased choices, the right inferior frontal gyrus, often implicated in inhibiting prepotent responses, connected more strongly with the striatum when subjects successfully overrode the decoy effect and made unbiased choices. This is further supported by our transcranial magnetic stimulation experiment: subjects whose right inferior frontal gyrus was temporarily disrupted made biased choices more often than a control group. Our results suggest that the neural basis of the decoy effect could be the context-dependent activation of the valuation area. But the differential connectivity from the frontal area may indicate how deliberate control monitors and corrects errors and biases in decision-making. SIGNIFICANCE STATEMENT Standard theories of rational decision-making assume context-independent valuations of available options. Motivated by the importance of this basic assumption, we used fMRI to study how the human brain assigns values to available options. We found activity in the valuation area to be consistent with the hypothesis that values depend on irrelevant aspects

Carp head kidney leukocytes display different patterns of oxygen radical production after stimulation with PAMPs and DAMPs

DEFF Research Database (Denmark)

Jiménez, Natalia Ivonne Vera; Nielsen, Michael Engelbrecht

2013-01-01

. Consistent with a pathogen eradication strategy, ROS responses to PAMP stimulation (β-glucan) was fast, vigorous and highly dominated by production of superoxide anion. In contrast, stimulation with DAMPs led to a slow, subtle but long-lasting production of oxygen radicals dominated by hydrogen peroxide....... Using an in vitro model of scratch-wounded CCB fibroblast cell cultures and a novel PhotoID proliferation assay, stimulation with low and continuous levels of hydrogen peroxide (5μM) led to a slight increase in the percentage of wound recovery and thus promoted wound closure. In contrast, high doses...... and thereby potential tissue damage. Direct in vitro stimulation with β-glucans did not impact fibroblast scratch-wound recovery, which further suggests that interaction with tissue-resident leukocytes or other components of the fish immune system are required to induce fibroblast proliferation and thus...

Neighborhood fast food availability and fast food consumption.

Science.gov (United States)

Oexle, Nathalie; Barnes, Timothy L; Blake, Christine E; Bell, Bethany A; Liese, Angela D

2015-09-01

Recent nutritional and public health research has focused on how the availability of various types of food in a person's immediate area or neighborhood influences his or her food choices and eating habits. It has been theorized that people living in areas with a wealth of unhealthy fast-food options may show higher levels of fast-food consumption, a factor that often coincides with being overweight or obese. However, measuring food availability in a particular area is difficult to achieve consistently: there may be differences in the strict physical locations of food options as compared to how individuals perceive their personal food availability, and various studies may use either one or both of these measures. The aim of this study was to evaluate the association between weekly fast-food consumption and both a person's perceived availability of fast-food and an objective measure of fast-food presence - Geographic Information Systems (GIS) - within that person's neighborhood. A randomly selected population-based sample of eight counties in South Carolina was used to conduct a cross-sectional telephone survey assessing self-report fast-food consumption and perceived availability of fast food. GIS was used to determine the actual number of fast-food outlets within each participant's neighborhood. Using multinomial logistic regression analyses, we found that neither perceived availability nor GIS-based presence of fast-food was significantly associated with weekly fast-food consumption. Our findings indicate that availability might not be the dominant factor influencing fast-food consumption. We recommend using subjective availability measures and considering individual characteristics that could influence both perceived availability of fast food and its impact on fast-food consumption. If replicated, our findings suggest that interventions aimed at reducing fast-food consumption by limiting neighborhood fast-food availability might not be completely effective

Serum Lipid Profile: Fasting or Non-fasting?

OpenAIRE

Nigam, P. K.

2010-01-01

Serum lipid profile has now become almost a routine test. It is usually done in fasting state due to certain limitations in non-fasting serum sample. In the recent past efforts have been made to simplify blood sampling by replacing fasting lipid profile with non-fasting lipid profile. However, fasting specimen is preferred if cardiovascular risk assessment is based on total cholesterol, LDL cholesterol or non-HDL cholesterol. A lot has yet to be done in this area. Till then we have to believe...

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

Science.gov (United States)

Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

Fast form alpha-2-macroglobulin

DEFF Research Database (Denmark)

Biltoft, Daniel; Gram, Jørgen Brodersen; Larsen, Anette

2017-01-01

Objectives: Investigation of the blood compatibility requires a number of sensitive assays to quantify the activation of the blood protein cascades and cells induced by biomaterials. A global assay measuring the blood compatibility of biomaterials could be a valuable tool in such regard....... In this study, we investigated whether an enzyme-linked immunosorbent assay (ELISA), that specifically measures the electrophoretic "fast form" of α2-macroglobulin (F-α2M), could be a sensitive and global marker for activation of calcium dependent and in-dependent proteases in plasma exposed to biomaterials...... in vitro. Methods: A F-α2M specific monoclonal antibody was generated and applied in an ELISA setup. Using the F-α2M ELISA, we investigated activation of calcium dependent and in-dependent proteases by polyvinylchloride (n=10), polytetrafluoroethylene (n=10) and silicone (n=10) tubings as well as glass...

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

Science.gov (United States)

Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Dosimetry based on thermally and optically stimulated luminescence

International Nuclear Information System (INIS)

Agersnap Larsen, Niels

1999-01-01

Thermally Stimulated Luminescence (TL) and Optically Stimulated Luminescence (OSL) properties of quartz and α-Al 2 O 3 have been investigated. Anneling-induced OSL and TL sensitivity changes in quartz has been investigated by experiments and modelling. This study does not support a pre-dose effect to account for the observed annealing-induced sensitivity change. The experimental data indicates a more simple mechanism that involves alteration of the concentration of the defect centers. Results from modelling of removal or creation of defect centers comparing well with experimentally obtained data. Thermal quenching of luminescence for the main emission center, the F-center, in α-Al 2 O 3 :C has been investigated by analysing TL curves obtained at different heating rates. The thermal quenching dependence of luminescence is found to follow the classical Mott-Seitz expression. Basic investigations of OSL properties of αAl 2 O 3 :C, including: the thermal depth of the OSL traps, the temperature dependence of OSL, and the OSL stimulation spectra. Simultaneous measurements of TL and thermally stimulated conductivity (TSC) are presented for γ-irradiated αAl 2 O 3 :C. Activation energy analysis of the data reveals a superposition of several first-order TL and TSC peaks caused by release of charge carriers from a distribution of trapping states. Furthermore a description of an experimental method developed to determine the sign of the thermally released charge carriers has been presented. (au)

Fast-food exposure around schools in urban Adelaide.

Science.gov (United States)

Coffee, Neil T; Kennedy, Hannah P; Niyonsenga, Theo

2016-12-01

To assess whether exposure to fast-food outlets around schools differed depending on socio-economic status (SES). Binary logistic regression was used to investigate the presence and zero-inflated Poisson regression was used for the count (due to the excess of zeroes) of fast food within 1000 m and 15000 m road network buffers around schools. The low and middle SES tertiles were combined due to a lack of significant variation as the 'disadvantaged' group and compared with the high SES tertile as the 'advantaged' group. School SES was expressed using the 2011 Australian Bureau of Statistics, socio-economic indices for areas, index of relative socio-economic disadvantage. Fast-food data included independent takeaway food outlets and major fast-food chains. Metropolitan Adelaide, South Australia. A total of 459 schools were geocoded to the street address and 1000 m and 1500 m road network distance buffers calculated. There was a 1·6 times greater risk of exposure to fast food within 1000 m (OR=1·634; 95 % 1·017, 2·625) and a 9·5 times greater risk of exposure to a fast food within 1500 m (OR=9·524; 95 % CI 3·497, 25·641) around disadvantaged schools compared with advantaged schools. Disadvantaged schools were exposed to more fast food, with more than twice the number of disadvantaged schools exposed to fast food. The higher exposure to fast food near more disadvantaged schools may reflect lower commercial land cost in low-SES areas, potentially creating more financially desirable investments for fast-food developers.

Testosterone suppression of CRH-stimulated cortisol in men.

Science.gov (United States)

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

2005-10-01

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

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

Science.gov (United States)

Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

Testing of a highly reconfigurable processor core for dependable data streaming applications

NARCIS (Netherlands)

Kerkhoff, Hans G.; Huijts, J.J.M.

2008-01-01

The advances of CMOS technology towards 45 nm,the high costs of ASIC design, power limitations and fast changing application requirements have stimulated the usage of highly reconfigurable multiprocessor-cores SoCs. These processing cores within the SoC can be subsequently connected with each other

Biophysical methods for disinfection and stimulation of wheat seeds

International Nuclear Information System (INIS)

Marinkovic, S.; Marinkovic, B.

2007-01-01

In this paper we are shown results of applying electron treatment (disinfection of seed by electrons), and RIES method (electromagnetic seed stimulation). Four cultivars of wheat were used in this trial: Renesansa, Durumko, NS-Rana 5 and Sonata. Seed was treated with fast electrons and just before sowing stimulated by ultra low frequency electromagnetic field (from 0 to 100 Hz). For seed disinfection was used chemical treatment as well, as control variant. Control variant for all treatments was seed without any disinfection. The highest number of spikelets per spike was obtained at variant H+RIES. The highest spike length was obtained at variants e sup(-) + RIES and control. At variant H+RIES was achieved the highest grain number. Treatment H had influence on decreasing of grain mass per spike in relation to control variant, for significant value of 0.15 g. The highest grain mass per spike was obtained at variant e sup(-) + RIES

A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo.

Directory of Open Access Journals (Sweden)

Peter Jedlicka

2015-11-01

Full Text Available Long-term potentiation (LTP and long-term depression (LTD are widely accepted to be synaptic mechanisms involved in learning and memory. It remains uncertain, however, which particular activity rules are utilized by hippocampal neurons to induce LTP and LTD in behaving animals. Recent experiments in the dentate gyrus of freely moving rats revealed an unexpected pattern of LTP and LTD from high-frequency perforant path stimulation. While 400 Hz theta-burst stimulation (400-TBS and 400 Hz delta-burst stimulation (400-DBS elicited substantial LTP of the tetanized medial path input and, concurrently, LTD of the non-tetanized lateral path input, 100 Hz theta-burst stimulation (100-TBS, a normally efficient LTP protocol for in vitro preparations produced only weak LTP and concurrent LTD. Here we show in a biophysically realistic compartmental granule cell model that this pattern of results can be accounted for by a voltage-based spike-timing-dependent plasticity (STDP rule combined with a relatively fast Bienenstock-Cooper-Munro (BCM-like homeostatic metaplasticity rule, all on a background of ongoing spontaneous activity in the input fibers. Our results suggest that, at least for dentate granule cells, the interplay of STDP-BCM plasticity rules and ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighboring non-tetanized inputs, as generated by the ongoing constitutive activity at these synapses.

Neuromuscular Electrical Stimulation for Mobility Support of Elderly.

Science.gov (United States)

Mayr, Winfried

2015-08-24

The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in "compliance data storage" as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

Neuromuscular electrical stimulation for mobility support of elderly

Directory of Open Access Journals (Sweden)

Winfried Mayr

2015-10-01

Full Text Available The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in “compliance data storage” as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC and maximum stimulation induced contraction (MSC were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

Science.gov (United States)

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-08-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

Science.gov (United States)

Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

2018-01-01

Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

Effect of anatomical variability in brain on transcranial magnetic stimulation treatment

Science.gov (United States)

Syeda, F.; Magsood, H.; Lee, E. G.; El-Gendy, A. A.; Jiles, D. C.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

Temperature dependences in electron-stimulated desorption of neutral europium

CERN Document Server

Ageev, V N; Madey, T E

2003-01-01

The electron-stimulated desorption (ESD) yield for neutral europium (Eu) atoms from Eu layers adsorbed on oxygen-covered tungsten surfaces has been measured as a function of electron energy, europium coverage and degree of oxidation of tungsten, with an emphasis on effects of substrate temperature. The measurements have been carried out using a time-of-flight method and surface ionization detector. We expand on an earlier report, and compare ESD of multivalent Eu with ESD of monovalent alkali atoms, studied previously. The Eu atom ESD is a complicated function of Eu coverage, electron energy and substrate temperature. In the coverage range 0.05-0.35 monolayer (ML), overlapping resonant-like Eu atom yield peaks are observed at electron energies E sub e of 36 and 41 eV that might be associated with Eu or W shallow core level excitations. Additional resonant-like peaks are seen at E sub e of 54 and 84 eV that are associated with W 5p and 5s level excitations. The Eu atom yield peaks at 36 and 41 eV are seen only...

Computational electromagnetic methods for transcranial magnetic stimulation

Science.gov (United States)

Gomez, Luis J.

Transcranial magnetic stimulation (TMS) is a noninvasive technique used both as a research tool for cognitive neuroscience and as a FDA approved treatment for depression. During TMS, coils positioned near the scalp generate electric fields and activate targeted brain regions. In this thesis, several computational electromagnetics methods that improve the analysis, design, and uncertainty quantification of TMS systems were developed. Analysis: A new fast direct technique for solving the large and sparse linear system of equations (LSEs) arising from the finite difference (FD) discretization of Maxwell's quasi-static equations was developed. Following a factorization step, the solver permits computation of TMS fields inside realistic brain models in seconds, allowing for patient-specific real-time usage during TMS. The solver is an alternative to iterative methods for solving FD LSEs, often requiring run-times of minutes. A new integral equation (IE) method for analyzing TMS fields was developed. The human head is highly-heterogeneous and characterized by high-relative permittivities (107). IE techniques for analyzing electromagnetic interactions with such media suffer from high-contrast and low-frequency breakdowns. The novel high-permittivity and low-frequency stable internally combined volume-surface IE method developed. The method not only applies to the analysis of high-permittivity objects, but it is also the first IE tool that is stable when analyzing highly-inhomogeneous negative permittivity plasmas. Design: TMS applications call for electric fields to be sharply focused on regions that lie deep inside the brain. Unfortunately, fields generated by present-day Figure-8 coils stimulate relatively large regions near the brain surface. An optimization method for designing single feed TMS coil-arrays capable of producing more localized and deeper stimulation was developed. Results show that the coil-arrays stimulate 2.4 cm into the head while stimulating 3

Further investigations into pulsed optically stimulated luminescence from feldspars using blue and green light

International Nuclear Information System (INIS)

Ankjaergaard, C.; Jain, M.; Kalchgruber, R.; Lapp, T.; Klein, D.; McKeever, S.W.S.; Murray, A.S.; Morthekai, P.

2009-01-01

The purpose of this paper is to investigate characteristics of luminescence signals resulting from pulsed optical stimulation of feldspars and thereby to understand the underlying processes giving rise to the signal. Fourteen different feldspar specimens were investigated using time-resolved optically stimulated luminescence (TR-OSL), and these signals can be mathematically described as a sum of 4 exponential components (a, b, c, d). The slowest component, d, increases with the duration of the light pulse as expected from the exponential model. The stimulation temperature dependence experiment suggests that the TR-OSL signal decay is governed by the recombination process and not by the excited state lifetime. Furthermore data from the TR-OSL signal dependence on stimulation time and preheat temperature suggest that the recombination process may not be a sum of exponentials, although the model cannot be rejected definitively.

Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.

Science.gov (United States)

Kawahara, Y; Nakase, Y; Isomoto, Y; Matsuda, N; Amagase, K; Kato, S; Takeuchi, K

2011-08-01

We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.

Unilateral phrenic nerve stimulation for neurogenic hypoventilation in Arnold Chiari malformation

Directory of Open Access Journals (Sweden)

Nitin Garg

2013-01-01

Full Text Available Long- term ventilator dependence in patients with neurogenic hypoventilation is associated with significant morbidity and restricts mobility. Diaphragmatic pacing by phrenic nerve stimulation (PNS is a viable alternative. This is a case report of patient with Arnold-Chiari malformation with extensive syrinx who had neurogenic hypoventilation during sleep even after foramen magnum decompression and resolution of the syrinx. Unilateral PNS was done using spinal cord stimulator. With intermittent stimulation for 8 h while asleep, patient could be weaned off the ventilator completely. At 2 years follow- up, patient is ambulant and has returned to his routine activities. PNS is a good treatment tool in patients with neurogenic hypoventilation. Spinal cord stimulator can be used with optimal results. This is first such reported case of using spinal cord stimulator for PNS from India.

Fast decay of iconic memory in observers with mild cognitive impairments

OpenAIRE

Lu, Zhong-Lin; Neuse, James; Madigan, Stephen; Dosher, Barbara Anne

2005-01-01

In a previous clinical report, unusually fast decay of iconic memory was obtained from a subject who later developed Alzheimer's disease. By using the partial-report paradigm, iconic memory (a form of visual sensory memory) in a group of observers with mild cognitive impairments (MCI) was characterized and compared with that of young college-age adults and older controls. Relatively long stimulus exposures were used for all three groups to ensure that older observers could perceive the stimul...

The correlation of fast OSL component with the TL peak at 3250C in quartz of various origins

International Nuclear Information System (INIS)

Kitis, G.; Kiyak, N.; Polymeris, G.S.; Tsirliganis, N.C.

2010-01-01

The fast component of the optically stimulated luminescence (OSL) signal in quartz is the basic tool for the optical dating. Its relation with the thermoluminescence (TL) glow-peak at about 325 deg. C is well established for naturally irradiated quartz. This relationship is also an important part of a general model for quartz on which many theoretical simulations of various OSL experimental results have been based. In the present work this relationship is systematically investigated in nine quartz samples of different origin. The linearly modulated OSL (LM-OSL) curves of all quartz samples for stimulation time less than 50 s consists of two components discriminated easily by a computerized curve deconvolution (CCD) analysis. By comparing the un-bleached to the respective bleached TL glow-curve, it is found that the system of these two fast OSL components is directly related with only a small portion of the electron traps responsible for the TL glow-peaks in the temperature region 200-400 0 C. By increasing the stimulation times, besides the two fast components, the medium and the slow components are also obtained. The medium and slow components are clearly related with the main body of the electron traps responsible for TL glow-peaks in the same temperature region 200-400 0 C. Despite their different origin all quartz samples show an appreciable homogeneity concerning the number and time position of the individual components, whereas, the relative TL/OSL intensities vary strongly from sample to sample with the integrated TL intensity being generally much less than the integrated OSL intensity.

Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle

DEFF Research Database (Denmark)

Cantó, Carles; Jiang, Lake Q; Deshmukh, Atul S

2010-01-01

During fasting and after exercise, skeletal muscle efficiently switches from carbohydrate to lipid as the main energy source to preserve glycogen stores and blood glucose levels for glucose-dependent tissues. Skeletal muscle cells sense this limitation in glucose availability and transform...... and lipid utilization genes. Deficient AMPK activity compromises SIRT1-dependent responses to exercise and fasting, resulting in impaired PGC-1alpha deacetylation and blunted induction of mitochondrial gene expression. Thus, we conclude that AMPK acts as the primordial trigger for fasting- and exercise...

LM-OSL signals from some insulators: an analysis of the dependency of the detrapping probability on stimulation light intensity

DEFF Research Database (Denmark)

Bulur, E.; Bøtter-Jensen, L.; Murray, A.S.

2001-01-01

Optically stimulated luminescence (OSL) signals from various insulators including quartz, Al2O3 : C, BeO and NaCl have been studied using the linear modulation OSL (LM-OSL) technique. LM-OSL is based on the linear increase of the stimulation light power from zero to a maximum during the measurement...... is not always correct. The initial decay rates of the blue (similar to 470 nm) light stimulated constant power OSL decay curves were examined to test the relation between the detrapping rates and the stimulation light intensity. In SiO2, Al2O3 : C and BeO a linear relation between the detrapping rates....... The resultant OSL curve initially increases and then decays after reaching a maximum, The analysis of LM-OSL data usually assumes a linear relationship between the detrapping rate and the stimulation light intensity. However, experiments carried out using various insulators have shown that this assumption...

Fast neutron radiotherapy: for equal or for better

International Nuclear Information System (INIS)

Broerse, J.J.; Battermann, J.J.

1981-01-01

The renewed application of fast neutrons in clinical radiotherapy has been stimulated by fundamental radiobiological findings. The biological effects of high LET radiation, including fast neutrons, are different from those obtained with x rays in at least three respects: the oxygen enhancement ratio, the sensitivity of cells at different phases of the cell cycle, and the contribution of sublethal damage to cell reproductive death. Furthermore, wide variations in relative biological effectiveness (RBE) have been observed for different tumors and normal tissues. Measurements of volume changes in human pulmonary metastases indicate that the RBE for slowly growing tumors which are generally well-differentiated is higher than that for poorly differentiated lesions. Six thousand patients have now been treated with fast neutron beams. The results of the clinical applications vary according to the method of application and to the type of cancer involved: treatment of inoperable malignancies of the salivary gland is very encouraging: the therapeutic gain is rather small for bladder and rectal cancers, soft tissue sarcomas and advanced carcinomas of the cervix; the responses of brain tumors are very disappointing. Most neutron radiotherapy applications have been less than optimal because of inadequate physical and technical conditions. Despite these difficulties, some interesting clinical data have become available. Due to the technical shortcomings, the possible advantages of fast neutrons are probably underestimated for many tumor sites. Well-designed clinical trials, preferably performed with high energy cyclotrons in clinical environments, will provide a decisive answer to the question of the usefulness of the new radiation modality

The age related slow and fast contributions to the overall changes in tibialis anterior contractile features disclosed by maximal single twitch scan.

Science.gov (United States)

Orizio, Claudio; Cogliati, Marta; Bissolotti, Luciano; Diemont, Bertrand; Gobbo, Massimiliano; Celichowski, Jan

2016-01-01

This work aimed to verify if maximal electrically evoked single twitch (STmax) scan discloses the relative functional weight of fast and slow small bundles of fibres (SBF) in determining the contractile features of tibialis anterior (TA) with ageing. SBFs were recruited by TA main motor point stimulation through 60 increasing levels of stimulation (LS): 20 stimuli at 2Hz for each LS. The lowest and highest LS provided the least ST and STmax, respectively. The scanned STmax was decomposed into individual SBF STs. They were identified when twitches from adjacent LS were significantly different and then subtracted from each other. Nine young (Y) and eleven old (O) subjects were investigated. Contraction time (CT) and STarea/STpeak (A/PT) were calculated per each SBF ST. 143 and 155 SBF STs were obtained in Y and O, respectively. Y: CT and A/PT range: 45-105ms and 67-183mNs/mN, respectively. Literature data set TA fast fibres at 34% so, from the arrays of CT and A/PT, 65ms and 100mNs/mN were identified as the upper limit for SBF fast ST classification. O: no SBF ST could be classified as fast. STmax scan reveals age-related changes in the relative contribution of fast and slow SBFs to the overall muscle mechanics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Uncovering the mechanism(s) of deep brain stimulation

International Nuclear Information System (INIS)

Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y

2005-01-01

Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS

Ultraviolet Stimulated Emission from Sol-Gel Spin Coated ZnO Thin Films

Directory of Open Access Journals (Sweden)

Ahmed S. Razeen

2017-01-01

Full Text Available Low cost ultraviolet stimulated emission has been generated using optical excitation of ZnO thin films deposited by sol-gel spin coating on n+ As-doped 100 Si-substrate. The number of deposited layers and the heat treatment have been investigated to obtain a film that can generate stimulated emission under optical excitation. The optimum condition for preparation of the film has been presented. X-ray diffraction and scanning electron microscope have been used for structural and morphological investigations. Input-output intensity dependence and spectral width, peak emission wavelength, and the quantum efficiency versus the pump intensity have been presented. A quantum efficiency of about 24.2% has been reported, a power exponent higher than 8 has been obtained in input-output intensity dependence, and a threshold of about 23 Mw/cm2 has been evaluated for the samples. The mechanism by which stimulated emission occurs has been discussed. The results show that sol-gel spin coating is a promising method for generating ultraviolet stimulated emission from ZnO thin films.

Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

Science.gov (United States)

Grisendi, Valentina; La Marca, Antonio

2017-06-01

In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

Intermittent stimulation delays adaptation to electrocutaneous sensory feedback

NARCIS (Netherlands)

Buma, D.G.; Buma, Dorindo G.; Buitenweg, Jan R.; Veltink, Petrus H.

Electrotactile displays deliver information to the user by means of electrocutaneous stimulation. If such displays are used in prostheses, the functionality depends on long term stability of this information channel. The perceived sensation, however, decays within 15 min due to central adaptation if

Analysis of criticality safety of coupled fast-thermal core 'HERBE'

International Nuclear Information System (INIS)

Pesic, M.

1991-01-01

Power excursion during possible fast core flooding is analyzed as serious accident. Model gives short filling time of fast zone with moderator after break of fast core tank. Reactivity increase is determined by computer codes and verified in specific experiments. Measurements of safety rods drop time and reactivity worth are performed. Coupled core kinetics parameters are determined according to model of Avery. Power excursion study, depending on power level threshold and safety instrumentation response time is performed. It was shown that safety system can shut-down reactor safely even in case of highly set power thresholds and partially failure of safety chain. (author)

Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

International Nuclear Information System (INIS)

Akter, Jesmin; Takatori, Atsushi; Islam, Md. Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

2014-01-01

Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas

Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

Energy Technology Data Exchange (ETDEWEB)

Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

2014-10-10

Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

Closing the loop of deep brain stimulation

Science.gov (United States)

Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

2013-01-01

High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

Closing the loop of deep brain stimulation.

Science.gov (United States)

Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

2013-12-20

High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

Closing the loop of deep brain stimulation

Directory of Open Access Journals (Sweden)

Romain eCARRON

2013-12-01

Full Text Available High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfils these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

Stimulation of the sensory pudendal nerve increases bladder capacity in the rat.

Science.gov (United States)

Hokanson, James A; Langdale, Christopher L; Sridhar, Arun; Grill, Warren M

2018-04-01

Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some promising clinical studies, there remain many unknowns as to how best to stimulate the pudendal nerve to maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry in response to electrical stimulation of the sensory branch of the pudendal nerve in urethane-anesthetized female Wistar rats. Increases in bladder capacity were dependent on both stimulation amplitude and rate. Stimulation that produced increases in bladder capacity also led to reductions in voiding efficiency. Also, there was a stimulation carryover effect, and increases in bladder capacity persisted during several nonstimulated trials following stimulated trials. Intravesically administered PGE 2 reduced bladder capacity, producing a model of overactive bladder (OAB), and sensory pudendal nerve stimulation again increased bladder capacity but also reduced voiding efficiency. This study serves as a basis for future studies that seek to maximize the therapeutic efficacy of sensory pudendal nerve stimulation for the symptoms of OAB.

Fast to forgive, slow to retaliate: intuitive responses in the ultimatum game depend on the degree of unfairness.

Science.gov (United States)

Ferguson, Eamonn; Maltby, John; Bibby, Peter A; Lawrence, Claire

2014-01-01

Evolutionary accounts have difficulty explaining why people cooperate with anonymous strangers they will never meet. Recently models, focusing on emotional processing, have been proposed as a potential explanation, with attention focusing on a dual systems approach based on system 1 (fast, intuitive, automatic, effortless, and emotional) and system 2 (slow, reflective, effortful, proactive and unemotional). Evidence shows that when cooperation is salient, people are fast (system 1) to cooperate, but with longer delays (system 2) they show greed. This is interpreted within the framework of the social heuristic hypothesis (SHH), whereby people overgeneralize potentially advantageous intuitively learnt and internalization social norms to 'atypical' situations. We extend this to explore intuitive reactions to unfairness by integrating the SHH with the 'fast to forgive, slow to anger' (FFSA) heuristic. This suggests that it is advantageous to be prosocial when facing uncertainty. We propose that whether or not someone intuitively shows prosociality (cooperation) or retaliation is moderated by the degree (certainty) of unfairness. People should intuitively cooperate when facing mild levels of unfairness (fast to forgive) but when given longer to decide about another's mild level of unfairness should retaliate (slow to anger). However, when facing severe levels of unfairness, the intuitive response is always retaliation. We test this using a series of one-shot ultimatum games and manipulate level of offer unfairness (50:50 60:40, 70:30, 80:20, 90:10) and enforced time delays prior to responding (1s, 2s, 8s, 15s). We also measure decision times to make responses after the time delays. The results show that when facing mildly unfair offers (60:40) people are fast (intuitive) to cooperate but with longer delays reject these mildly unfair offers: 'fast to forgive, and slow to retaliate'. However, for severely unfair offers (90:10) the intuitive and fast response is to always

Fast to forgive, slow to retaliate: intuitive responses in the ultimatum game depend on the degree of unfairness.

Directory of Open Access Journals (Sweden)

Eamonn Ferguson

Full Text Available Evolutionary accounts have difficulty explaining why people cooperate with anonymous strangers they will never meet. Recently models, focusing on emotional processing, have been proposed as a potential explanation, with attention focusing on a dual systems approach based on system 1 (fast, intuitive, automatic, effortless, and emotional and system 2 (slow, reflective, effortful, proactive and unemotional. Evidence shows that when cooperation is salient, people are fast (system 1 to cooperate, but with longer delays (system 2 they show greed. This is interpreted within the framework of the social heuristic hypothesis (SHH, whereby people overgeneralize potentially advantageous intuitively learnt and internalization social norms to 'atypical' situations. We extend this to explore intuitive reactions to unfairness by integrating the SHH with the 'fast to forgive, slow to anger' (FFSA heuristic. This suggests that it is advantageous to be prosocial when facing uncertainty. We propose that whether or not someone intuitively shows prosociality (cooperation or retaliation is moderated by the degree (certainty of unfairness. People should intuitively cooperate when facing mild levels of unfairness (fast to forgive but when given longer to decide about another's mild level of unfairness should retaliate (slow to anger. However, when facing severe levels of unfairness, the intuitive response is always retaliation. We test this using a series of one-shot ultimatum games and manipulate level of offer unfairness (50:50 60:40, 70:30, 80:20, 90:10 and enforced time delays prior to responding (1s, 2s, 8s, 15s. We also measure decision times to make responses after the time delays. The results show that when facing mildly unfair offers (60:40 people are fast (intuitive to cooperate but with longer delays reject these mildly unfair offers: 'fast to forgive, and slow to retaliate'. However, for severely unfair offers (90:10 the intuitive and fast response is to

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

Science.gov (United States)

Santos-Pontelli, Taiza E G; Rimoli, Brunna P; Favoretto, Diandra B; Mazin, Suleimy C; Truong, Dennis Q; Leite, Joao P; Pontes-Neto, Octavio M; Babyar, Suzanne R; Reding, Michael; Bikson, Marom; Edwards, Dylan J

2016-01-01

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

Femtosecond Broadband Stimulated Raman Spectroscopy

International Nuclear Information System (INIS)

Lee, Soo-Y; Yoon, Sagwoon; Mathies, Richard A

2006-01-01

Femtosecond broadband stimulated Raman spectroscopy (FSRS) is a new technique where a narrow bandwidth picosecond Raman pump pulse and a red-shifted broadband femtosecond Stokes probe pulse (with or without time delay between the pulses) act on a sample to produce a high resolution Raman gain spectrum with high efficiency and speed, free from fluorescence background interference. It can reveal vibrational structural information and dynamics of stationary or transient states. Here, the quantum picture for femtosecond broadband stimulated Raman spectroscopy (FSRS) is used to develop the semiclassical coupled wave theory of the phenomenon and to derive an expression for the measurable Raman gain in FSRS. The semiclassical theory is applied to study the dependence of lineshapes in FSRS on the pump-probe time delay and to deduce vibrational dephasing times in cyclohexane in the ground state

The Fast-Casual Conundrum: Fast-Casual Restaurant Entrées Are Higher in Calories than Fast Food.

Science.gov (United States)

Schoffman, Danielle E; Davidson, Charis R; Hales, Sarah B; Crimarco, Anthony E; Dahl, Alicia A; Turner-McGrievy, Gabrielle M

2016-10-01

Frequently eating fast food has been associated with consuming a diet high in calories, and there is a public perception that fast-casual restaurants (eg, Chipotle) are healthier than traditional fast food (eg, McDonald's). However, research has not examined whether fast-food entrées and fast-casual entrées differ in calorie content. The purpose of this study was to determine whether the caloric content of entrées at fast-food restaurants differed from that found at fast-casual restaurants. This study was a cross-sectional analysis of secondary data. Calorie information from 2014 for lunch and dinner entrées for fast-food and fast-casual restaurants was downloaded from the MenuStat database. Mean calories per entrée between fast-food restaurants and fast-casual restaurants and the proportion of restaurant entrées that fell into different calorie ranges were assessed. A t test was conducted to test the hypothesis that there was no difference between the average calories per entrée at fast-food and fast-casual restaurants. To examine the difference in distribution of entrées in different calorie ranges between fast-food and fast-casual restaurants, χ(2) tests were used. There were 34 fast-food and 28 fast-casual restaurants included in the analysis (n=3,193 entrées). Fast-casual entrées had significantly more calories per entrée (760±301 kcal) than fast-food entrées (561±268; Prestaurants to determine whether the energy content or nutrient density of full meals (ie, entrées with sides and drinks) differs between fast-casual restaurants and fast-food restaurants. Calorie-conscious consumers should consider the calorie content of entrée items before purchase, regardless of restaurant type. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Membrane-associated proteolytic activity in Escherichia coli that is stimulated by ATP

International Nuclear Information System (INIS)

Klemes, Y.; Voellmy, R.W.; Goldberg, A.L.

1986-01-01

The degradation of proteins in bacteria requires metabolism energy. One important enzyme in this process is protease La, a soluble ATP-dependent protease encoded by the lon gene. However, lon mutants that lack a functional protease La still show some ATP-dependent protein breakdown. The authors have reported an ATP-stimulated endoproteolytic activity associated with the inner membrane of E. coli. This ATP-stimulated activity is found in normal levels in membranes derived from lon mutants, including strains carrying insertions in the lon gene. The membrane-bound activity hydrolyzes 14 C-methylglobin at a linear rate for up to 3 hours. These fractions also contain appreciable proteolytic activity that is not affected by ATP. The stimulation by ATP requires the presence of Mg 2+ . Nonhydrolyzable ATP analogs (e.g. AMPPNP or ATP-γ-S) and ADP do not enhance proteolysis. Unlike protease La, the membrane-associated enzyme does not degrade the fluorometric substrate, Glt-Ala-Ala-Phe-MNA, in an ATP-stimulated fashion, and its level is not influenced by high temperature of by the gene which regulates the heat-shock response. The enzyme is inhibited by dichloroisocoumarin and certain peptide chloromethyl ketones. They conclude that E. coli contain at least two ATP-dependent proteases with distinct specificities: one is soluble and the other is membrane-associated

Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults

DEFF Research Database (Denmark)

Laursen, Torben; Jørgensen, Jens Otto Lunde; Møller, Jens

1994-01-01

. CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused......Abstract OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose...... without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P

Augmented brain function by coordinated reset stimulation with slowly varying sequences

OpenAIRE

Magteld eZeitler; Peter A. Tass; Peter A. Tass; Peter A. Tass

2015-01-01

Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e. an unlearning of abnormal synaptic connectivity and abnormal sync...

Augmented brain function by coordinated reset stimulation with slowly varying sequences

OpenAIRE

Zeitler, Magteld; Tass, Peter A.

2015-01-01

Several brain disorders are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was developed to selectively counteract abnormal neuronal synchrony by desynchronization. For this, phase resetting stimuli are delivered to different subpopulations in a timely coordinated way. In neural networks with spike timing-dependent plasticity CR stimulation may eventually lead to an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and abnormal syn...

Nanosecond laser pulse stimulation of spiral ganglion neurons and model cells.

Science.gov (United States)

Rettenmaier, Alexander; Lenarz, Thomas; Reuter, Günter

2014-04-01

Optical stimulation of the inner ear has recently attracted attention, suggesting a higher frequency resolution compared to electrical cochlear implants due to its high spatial stimulation selectivity. Although the feasibility of the effect is shown in multiple in vivo experiments, the stimulation mechanism remains open to discussion. Here we investigate in single-cell measurements the reaction of spiral ganglion neurons and model cells to irradiation with a nanosecond-pulsed laser beam over a broad wavelength range from 420 nm up to 1950 nm using the patch clamp technique. Cell reactions were wavelength- and pulse-energy-dependent but too small to elicit action potentials in the investigated spiral ganglion neurons. As the applied radiant exposure was much higher than the reported threshold for in vivo experiments in the same laser regime, we conclude that in a stimulation paradigm with nanosecond-pulses, direct neuronal stimulation is not the main cause of optical cochlea stimulation.

Early Maladaptive Schemas in Opiate and Stimulant Users

Directory of Open Access Journals (Sweden)

Zahra Karami

2015-06-01

Full Text Available Objectives: Early maladaptive schemas are valid representations of unpleasant childhood experiences that shape a person’s viewpoints of the world, and lead to clinical symptoms such as depression, personality disorders, and substance abuse. Given the importance of this matter, we conducted a research on early maladaptive schemas in substance-abusers, to allow more appropriate preventive measures to be taken with a better understanding of the issue. Methods: For this descriptive-comparative study, 115 patients (91 opiate users and 24 stimulant users visiting drug addiction treatment centers were selected through convenience sampling from persons who were admitted to substance abuse treatment centers (Methadone Maintenance therapy centers, addiction treatment camps and self-help groups and Narcotics Anonymous (NA of Yasuj. Data were collected using a Demographic Information Questionnaire and Young’s Schema Questionnaire-Short Form (SQ-SF. Data analysis was done with ANOVA and t-tests. Results: The results showed a significant difference (P<0.05 between users of opiates and stimulants in terms of vulnerability to harm or illness, enmeshment, subjugation, emotional inhibition, entitlement, insufficient self-control/self-discipline, emotional  deprivation, social isolation, defectiveness, failure/shame, and dependence. The average score of the stimulant-users was higher than that of opiate-users in all the schemas except for the dimensions of abandonment, mistrust, and unrelenting standards. Discussion: Stimulant users have more early maladaptive schemas and are at a greater risk of psychological vulnerability. Early maladaptive schemas can be used by clinicians and researchers as a psychopathology and treatment method for substance dependence disorder.

Dosimetry based on thermally and optically stimulated luminescence

Energy Technology Data Exchange (ETDEWEB)

Agersnap Larsen, Niels

1999-01-01

Thermally Stimulated Luminescence (TL) and Optically Stimulated Luminescence (OSL) properties of quartz and {alpha}-Al{sub 2}O{sub 3} have been investigated. Anneling-induced OSL and TL sensitivity changes in quartz has been investigated by experiments and modelling. This study does not support a pre-dose effect to account for the observed annealing-induced sensitivity change. The experimental data indicates a more simple mechanism that involves alteration of the concentration of the defect centers. Results from modelling of removal or creation of defect centers comparing well with experimentally obtained data. Thermal quenching of luminescence for the main emission center, the F-center, in {alpha}-Al{sub 2}O{sub 3}:C has been investigated by analysing TL curves obtained at different heating rates. The thermal quenching dependence of luminescence is found to follow the classical Mott-Seitz expression. Basic investigations of OSL properties of {alpha}Al{sub 2}O{sub 3}:C, including: the thermal depth of the OSL traps, the temperature dependence of OSL, and the OSL stimulation spectra. Simultaneous measurements of TL and thermally stimulated conductivity (TSC) are presented for {gamma}-irradiated {alpha}Al{sub 2}O{sub 3}:C. Activation energy analysis of the data reveals a superposition of several first-order TL and TSC peaks caused by release of charge carriers from a distribution of trapping states. Furthermore a description of an experimental method developed to determine the sign of the thermally released charge carriers has been presented. (au) 8 tabs., 59 ills., 90 refs.

The galactic position dependence of fast radio bursts and the discovery of FRB011025

Energy Technology Data Exchange (ETDEWEB)

Burke-Spolaor, Sarah [California Institute of Technology, 1200 E California Blvd, Pasadena, CA (United States); Bannister, Keith W., E-mail: sarahbspolaor@gmail.com [CSIRO Astronomy and Space Sciences, P.O. Box 76, Epping NSW 1710 (Australia)

2014-09-01

We report the detection of a dispersed fast radio burst (FRB) in archival intermediate-latitude Parkes Radio Telescope data. The burst appears to be of the same physical origin as the four purported extragalactic FRBs reported by Thornton et al. This burst's arrival time precedes the Thornton et al. bursts by 10 years. We consider that this survey, and many other archival low-latitude (|gb| < 30°) pulsar surveys, have been searched for FRBs but produced fewer detections than the comparatively brief Thornton et al. search. Such a rate dependence on Galactic position could provide critical supporting evidence for an extragalactic origin for FRBs. To test this, we form an analytic expression to account for Galactic position and survey setup in FRB rate predictions. Employing a sky temperature, scattering, and dispersion model of the Milky Way, we compute the expected number of FRBs if they are isotropically distributed on the sky with respect to the Galactic position (i.e., local), and if they are of extragalactic origin. We demonstrate that the relative detection rates reject a local origin with a confidence of 99.96% (∼3.6σ). The extragalactic predictions provide a better agreement; however, there are still strong discrepancies with the low-latitude detection rate at a confidence of 99.69% (∼2.9σ). However, for the extragalactic population, the differences in predicted versus detected population may be accounted for by a number of factors, which we discuss.

The galactic position dependence of fast radio bursts and the discovery of FRB011025

International Nuclear Information System (INIS)

Burke-Spolaor, Sarah; Bannister, Keith W.

2014-01-01

We report the detection of a dispersed fast radio burst (FRB) in archival intermediate-latitude Parkes Radio Telescope data. The burst appears to be of the same physical origin as the four purported extragalactic FRBs reported by Thornton et al. This burst's arrival time precedes the Thornton et al. bursts by 10 years. We consider that this survey, and many other archival low-latitude (|gb| < 30°) pulsar surveys, have been searched for FRBs but produced fewer detections than the comparatively brief Thornton et al. search. Such a rate dependence on Galactic position could provide critical supporting evidence for an extragalactic origin for FRBs. To test this, we form an analytic expression to account for Galactic position and survey setup in FRB rate predictions. Employing a sky temperature, scattering, and dispersion model of the Milky Way, we compute the expected number of FRBs if they are isotropically distributed on the sky with respect to the Galactic position (i.e., local), and if they are of extragalactic origin. We demonstrate that the relative detection rates reject a local origin with a confidence of 99.96% (∼3.6σ). The extragalactic predictions provide a better agreement; however, there are still strong discrepancies with the low-latitude detection rate at a confidence of 99.69% (∼2.9σ). However, for the extragalactic population, the differences in predicted versus detected population may be accounted for by a number of factors, which we discuss.

Nonlinear joint angle control for artificially stimulated muscle

NARCIS (Netherlands)

Veltink, Petrus H.; Chizeck, Howard J.; Crago, Patrick E.; El-Bialy, Ahmed

1992-01-01

Designs of both open- and closed-loop controllers of electrically stimulated muscle that explicitly depend on a nonlinear mathematical model of muscle input-output properties are presented and evaluated. The muscle model consists of three factors: a muscle activation dynamics factor, an angle-torque

Fast, low noise transimpedance preamplifier

International Nuclear Information System (INIS)

Parlakyan, L.K.

1995-01-01

A single-channel transimpedance preamplifier for fast dielectric detectors is described. The main specifications of the preamplifier are: rise time is 1,5 ns; gain is 3,5 mV/μ A (with two section- 210 mV/μ A); r.m.s input noise is 30 n A; power consumption is 22 m W. Depending on supply voltage, the parameters may vary in a wide range. 5 refs

Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation.

Science.gov (United States)

Rodriguez-Falces, Javier; Place, Nicolas

2013-12-01

To investigate potential differences in the recruitment order of motor units (MUs) in the quadriceps femoris when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using femoral nerve stimulation and direct quadriceps stimulation of gradually increasing intensity from 20 young, healthy subjects. Recruitment order was investigated by analysing the time-to-peak twitch and the time interval from the stimulus artefact to the M-wave positive peak (M-wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles. During femoral nerve stimulation, time-to-peak twitch and M-wave latency decreased consistently (P  0.05). For the VM muscle, M-wave latency decreased with increasing stimulation level for both femoral nerve and direct quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave latency with stimulus intensity was different for the two stimulation geometries (P recruitment order during direct quadriceps stimulation was more complex, depending ultimately on the architecture of the peripheral nerve and its terminal branches below the stimulating electrodes for each muscle. For the VM, MUs were orderly recruited for both stimulation geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral nerve stimulation, but followed no particular order for direct quadriceps stimulation.

Technical review of the high energy gas stimulation technique

Energy Technology Data Exchange (ETDEWEB)

Haney, B.; Cuthill, D. [Computalog Ltd., Calgary, AB (Canada)

1997-08-01

High Energy Gas Stimulation (HEGS) or propellant stimulation is a process that enhances production of oil wells by decreasing wellbore damage and increasing near wellbore permeability. The technique has been used on about 7,000 wells with varying results. The HEGS tool is a cast cylinder of solid rocket propellant with a central ignition system. The propellant is fired and as it burns it produces a pressure load on the formation, increasing fracture volume which enhances the flow channels. Background information on the development and application of this stimulation technique was provided. The introduction of fractures around a wellbore is dependent on the pressure loading rate and the dynamic response of the rock. Propellant stimulation relies on controlling the pressure-time behaviour to maximize fracture growth by fluid pressurization. The process is composed of 3 sequential phases: (1) wellbore pressurization, (2) fracture initiation, and (3) fracture extension. A full description of each of these phases was provided. Geologic and well-tool factors that have a significant influence on the fracturing process such as in-situ stress, natural fractures and flaws, formation mechanical properties, formation fluid and flow properties, formation thermal properties, and wellbore, tool, and tamp configuration, were also reviewed. The many applications for HEGS were presented. It was emphasized that the success of HEGS is dependent on pre-stimulation problem evaluation and on proper charge design. Since HEGS will decrease near-wellbore restrictions and initiate formation breakdown, it should only be used in cases where this will be beneficial to the well. Careful attention to engineering will optimize results. 21 refs., 13 figs.

The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

Directory of Open Access Journals (Sweden)

Anna Sommansson

Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

Effect of sevoflurane on neuronal activity during deep brain stimulation surgery for epilepsy: A case report

OpenAIRE

Michaël J. Bos, MD; Linda Ackermans, MD, PhD; Frédéric L.W.V.J. Schaper, MD; Rob P.W. Rouhl, MD, PhD; Vivianne H.J.M. van Kranen-Mastenbroek, MD, PhD; Wolfgang F. Buhre, MD, PhD; Marcus L.F. Janssen, MD, PhD

2018-01-01

Deep brain stimulation of the anterior nucleus of the thalamus is an effective treatment for patients with refractory epilepsy who do not respond sufficiently to medical therapy. Optimal therapeutic effects of deep brain stimulation probably depend on accurate positioning of the stimulating electrodes. Microelectrode recordings show bursty firing neurons in the anterior nucleus of the thalamus region, which confirms the anatomical target determined by the surgeon. Deep brain stimulation elect...

Brain Stimulation Therapies

Science.gov (United States)

... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

Centre-surround organization of fast sensorimotor integration in human motor hand area

DEFF Research Database (Denmark)

Dubbioso, Raffaele; Raffin, Estelle; Karabanov, Anke

2017-01-01

Using the short-latency afferent inhibition (SAI) paradigm, transcranial magnetic stimulation (TMS) of the primary motor hand area (M1HAND) can probe how sensory input from limbs modulates corticomotor output in humans. Here we applied a novel TMS mapping approach to chart the spatial representat......Using the short-latency afferent inhibition (SAI) paradigm, transcranial magnetic stimulation (TMS) of the primary motor hand area (M1HAND) can probe how sensory input from limbs modulates corticomotor output in humans. Here we applied a novel TMS mapping approach to chart the spatial...... in M1HAND. Like homotopic SAI, heterotopic SAF was somatotopically expressed in M1HAND. Together, the results provide first-time evidence that fast sensorimotor integration involves centre-inhibition and surround-facilitation in human M1HAND....

Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs

International Nuclear Information System (INIS)

Tomoyasu, Akihiro; Higashio, Kanji; Kanomata, Kazuhiro; Goto, Masaaki; Kodaira, Kunihiko; Serizawa, Hiroko; Suda, Tatsuo; Nakamura, Atsushi; Nojima, Junya; Fukuda, Toru; Katagiri, Takenobu

2007-01-01

Platelet-rich plasma (PRP) is clinically used as an autologous blood product to stimulate bone formation in vivo. In the present study, we examined the effects of PRP on proliferation and osteoblast differentiation in vitro in the presence of bone morphogenetic proteins (BMPs). PRP and its soluble fraction stimulated osteoblastic differentiation of myoblasts and osteoblastic cells in the presence of BMP-2, BMP-4, BMP-6 or BMP-7. The soluble PRP fraction stimulated osteoblastic differentiation in 3D cultures using scaffolds made of collagen or hydroxyapatite. Moreover, heparin-binding fractions obtained from serum also stimulated osteoblastic differentiation in the presence of BMP-4. These results suggested that platelets contain not only growth factors for proliferation but also novel potentiator(s) for BMP-dependent osteoblastic differentiation

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

Science.gov (United States)

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

Directory of Open Access Journals (Sweden)

Magteld Zeitler

2018-05-01

Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

On the nanotoxicity of PAMAM dendrimers: Superfect® stimulates the EGFR-ERK1/2 signal transduction pathway via an oxidative stress-dependent mechanism in HEK 293 cells.

Science.gov (United States)

Akhtar, Saghir; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

2013-05-01

Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that may serve as drug delivery systems for gene-based therapies such as RNA interference. For their safe use in the clinic, they should ideally only enhance drug delivery to target tissues and exhibit no adverse effects. However, little is known about their toxicological profiles in terms of their interactions with cellular signal transduction pathways such as the epidermal growth factor receptor (EGFR). The EGFR is an important signaling cascade that regulates cell growth, differentiation, migration, survival and apoptosis. Here, we investigated the impact of naked, unmodified Superfect (SF), a commercially available generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR) tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in human embryonic kidney (HEK 293) cells. At concentrations routinely used for transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2 phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist, inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was partly reversible upon removal of the dendrimer and examination of cells 24 later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in greater EGFR stimulation than either agent alone implying that the stimulatory effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase and tempol implying that an oxidative stress dependent mechanism was involved. These results show for the first time that PAMAM dendrimers, aside from their ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular signal transduction pathway - a novel finding that may have a bearing on their safe application as drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of temperament and character personality traits in opiate and stimulant addicts

Directory of Open Access Journals (Sweden)

Fatemeh Sadeghi Pouya

2016-11-01

Full Text Available Background: Phenomenon of addiction as one of the social problems has a high prevalence, especially among youth. The aim of the present study was to compare personality traits based on the temperament and character inventory in opiate and stimulant addicts in Tehran.  Methods: In the present quasi-experimental study, 60 male addicts (30 opiate and 30 stimulant addicts who referred to addiction treatment centers in the suburbs of Tehran were selected through convenience sampling method and were studied using Temperament and Character Inventory (TCI. The participants were sorted according to their age and education.    Results: There was a significant difference between the two groups with regard to harm avoidance, reward dependence, cooperativeness, and self-transcendence traits. Thus, opiate addicts had higher levels of harm avoidance, reward dependence, and cooperativeness, and stimulant addicts had higher levels of self-transcendence. The significance level was set at P<0.01.  Conclusion: The obtained results showed that there was a significant difference between opiate and stimulant addicts. Opiate addicts gained higher scores, compared with stimulant addicts, in Temperament and Character Inventory variables. The obtained results also showed that stimulant addicts were suffering from more severe disorders than opiate addicts. Based on the means of the values of the TCI, personality traits reflecting personality disorders are detectable and predictable in substance abusers. This new understanding is important in the prevention and treatment of addiction.

Effect of Ramadan Fasting on Stress Neurohormones in Women with Polycystic Ovary Syndrome.

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Farideh Zangeneh

2015-06-01

Full Text Available To determine the effects of Ramadan fasting on serum levels of stress neurohormones in Iranian women with polycystic ovary syndrome (PCOS.This study was a clinical trial and was performed during July 2011 (month of Ramadan in Royan institute, Tehran. A total of 40 women who were aged 20-40 years and known cases of PCOS and had no other medical diseases were included in the study. They were divided into two groups as follows: (i study group (n = 20 who participated in Ramadan fasting and (ii control group (n = 20 who did not participate in fasting. For evaluating Ramadan's effect on the level of neurohormones serum level of the following variables were evaluated before and after Ramadan: cortisol, adrenaline (A, noradrenalin (NA, beta-endorphin (β-End, insulin, as well as sex hormones including follicle-stimulating hormone (FSH, luteinizing hormone (LH, and testosterone.In the study group after Ramadan serum cortisol and nor-adrenaline levels were significantly lower than the initial levels obtained at beginning of Ramadan (p < 0.05 as compared to control group.This study indicates that Ramadan fasting decreases stress neurohormones in women with PCOS.

"Fast" and "slow" skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method.

Science.gov (United States)

Jami, L; Lan-Couton, D; Malmgren, K; Petit, J

1978-07-01

The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast beta axons and to assess the total proportion of both fast and slow beta-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that beta axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag1 fibers in the others. As this latter location is characteristic of slow dynamic beta axons, it was concluded that both slow and fast beta axons occur regularly in the motor supply to tenuissimus. beta-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow beta axons onto the same spindle.

Excitatory amino acid-stimulated uptake of 22Na+ in primary astrocyte cultures

International Nuclear Information System (INIS)

Kimelberg, H.K.; Pang, S.; Treble, D.H.

1989-01-01

In this study we have found that L-glutamic acid, as well as being taken up by a Na+-dependent mechanism, will stimulate the uptake of 22Na+ by primary astrocyte cultures from rat brain in the presence of ouabain. By simultaneously measuring the uptake of 22Na+ and L-3H-glutamate a stoichiometry of 2-3 Na+ per glutamate was measured, implying electrogenic uptake. Increasing the medium K+ concentration to depolarize the cells inhibited L-3H-glutamate uptake, while calculations of the energetics of the observed L-3H-glutamate accumulation also supported an electrogenic mechanism of at least 2 Na+:1 glutamate. In contrast, kinetic analysis of the Na+ dependence of L-3H-glutamate uptake indicated a stoichiometry of Na+ to glutamate of 1:1, but further analysis showed that the stoichiometry cannot be resolved by purely kinetic studies. Studies with glutamate analogs, however, showed that kainic acid was a very effective stimulant of 22Na+ uptake, but 3H-kainic acid showed no Na+ -dependent uptake. Furthermore, while L-3H-glutamate uptake was very sensitive to lowered temperatures, glutamate-stimulated 22Na+ uptake was relatively insensitive. These results indicate that glutamate-stimulated uptake of 22Na+ in primary astrocytes cultures cannot be explained solely by cotransport of Na+ with glutamate, and they suggest that direct kainic acid-type receptor induced stimulation of Na+ uptake also occurs. Since both receptor and uptake effects involve transport of Na+, accurate measurements of the Na+ :glutamate stoichiometry for uptake can only be done using completely specific inhibitors of these 2 systems

Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

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Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

2011-08-01

Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

On stimulated scattering of laser light in inertial fusion energy targets

International Nuclear Information System (INIS)

Nikolic, Lj; Skoric, M.M.; Ishiguro, S.; Sato, T.

2002-11-01

Propagation of a laser light through regions of an underdense plasma is an active research topic in laser fusion. In particular, a large effort has been invested in studies of stimulated Raman scattering (SRS) and stimulated Brillouin scattering (SBS) which can reflect laser energy and produce energetic particles to preheat a fusion energy target. Experiments, theory and simulations agree on a complex interplay between various laser-plasma instabilities. By particle-in-cell simulations of an underdense electron-plasma, we have found, apart from the standard SRS, a strong backscattering near the electron plasma frequency at densities beyond the quarter critical. This novel instability, recognized in recent experiments as stimulated laser scattering on a trapped electron-acoustic mode (SEAS), is absent from a classical theory of laser-parametric instabilities. A parametric excitation of SEAS instability, is explained by a three-wave resonant decay of the incident laser light into a standing backscattered wave and a slow trapped electron acoustic wave (ω p ). Large SEAS pulsations, eventually suppressed by relativistic heating of electrons, are observed in our simulations. This phenomenon seems relevant to future hohlraum target and fast ignition experiments. (author)

Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells.

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Velagapudi, Ravikanth; Baco, Gina; Khela, Sunjeet; Okorji, Uchechukwu; Olajide, Olumayokun

2016-06-01

Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells. An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1β-stimulated SK-N-SH cells. Expression of COX-2, phospho-IκB, and phospho-IKK proteins was evaluated, while NF-κB reporter gene assay was carried out in TNFα-stimulated HEK293 cells to determine the effect of PWE on NF-κB transactivation. Levels of BACE-1 and Aβ in SK-N-SH cells stimulated with IL-1β were measured with an in cell ELISA. PWE (25-200 μg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1β. Phosphorylation of IκB and IKK was significantly (p pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1β-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease.

Fast Convolution Module (Fast Convolution Module)

National Research Council Canada - National Science Library

Bierens, L

1997-01-01

This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

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Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

Science.gov (United States)

Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

Science.gov (United States)

Ho, Elton; Smith, Richard; Goetz, Georges; Lei, Xin; Galambos, Ludwig; Kamins, Theodore I; Harris, James; Mathieson, Keith; Palanker, Daniel; Sher, Alexander

2018-02-01

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-μm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 μm (mean ± SE), similar to that of visual responses (221 ± 4 μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We