Acute resistance exercise reduces blood pressure and vascular reactivity, and increases endothelium-dependent relaxation in spontaneously hypertensive rats.

PubMed

Faria, Thaís de Oliveira; Targueta, Gabriel Pelegrineti; Angeli, Jhuli Keli; Almeida, Edna Aparecida Silveira; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

2010-09-01

The aim of the present study was to assess the effects of acute dynamic resistance exercise on resting blood pressure (BP) and on endothelial function of vascular bed of spontaneously hypertensive rats. Hemodynamic measurements were performed before and after acute dynamic resistance exercise in conscious animals. After exercise, the tail artery was cannulated for mean perfusion pressure with constant flow measurement and for performing concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) and dose-response curves to phenylephrine (PHE). PHE protocol was also repeated with damaged endothelium and after L-NAME and indomethacin perfusion on the tail. The maximal response (E(max)) and sensitivity (pD(2)) were evaluated to these drugs. Exercise reduced resting systolic and diastolic BP (Delta -79 +/- 1.8; -23 +/- 2.3 mmHg, respectively; P < 0.05). ACh-induced relaxation increased in the exercise group (pD(2) = 9.8 +/- 0.06, P < 0.05) when compared with control rats (pD(2) = 8.7 +/- 0.1). The E(max) to PHE with intact endothelium decreased following exercise condition (439 +/- 18 mmHg, P < 0.05) when compared with control rats (276 +/- 22 mmHg). This response was abolished after L-NAME and indomethacin administration. After damage of the endothelium, PHE responses were not significantly different between the groups; however, E(max) and pD(2) increased when compared with responses obtained with intact endothelium. The results demonstrated that acute dynamic resistance exercise decreased resting BP and reactivity to PHE and increased endothelium-dependent relaxation. Nitric oxide and vasodilators prostanoids appear to be involved in post-exercise endothelial and pressor responses.

The Acute Effects of Hold-Relax Proprioceptive Neuromuscular Facilitation With Vibration Therapy on Glenohumeral Internal-Rotation Deficit.

PubMed

Tucker, W Steven; Slone, Stephen W

2016-08-01

Clinicians use various stretching techniques to prevent the onset of and treat glenohumeral internal-rotation deficit (GIRD). It is unknown which stretching technique is the most effective. To investigate the acute effects of hold-relax proprioceptive neuromuscular facilitation (PNF) with and without vibration therapy on internal rotation in individuals with GIRD. 2-within (stretch × time) comparison with repeated measures. Controlled laboratory. 11 male current and former overhead athletes (19.8 ± 1.4 y, 184.5 ± 4.5 cm, 91.8 ± 11.6 kg) who presented with GIRD. At 3 separate sessions, participants performed 1 of 3 randomly assigned stretches: hold-relax PNF (PNF), hold-relax PNF in combination with a whole-body-vibration unit set at 30 Hz (PNF-V), and static stretch (SS). Pretest and posttest maximum passive glenohumeral internal-rotation measurements were taken with a digital protractor. The dependent variables were the mean glenohumeral internal-rotation measurements taken at the pretest and posttest. The influence of stretch (PNF, PNF-V, and SS) and time (pretest and posttest) on mean glenohumeral internal rotation was compared using a 3 × 2 factorial ANOVA with repeated measures on both variables (P ≤ .05). There was a stretch-by-time interaction (F2,20 = 34.697, P < .001). Post hoc testing revealed that the PNF posttest (73.0° ± 10.4°) was greater than the PNF pretest (60.0° ± 11.8°), the PNF-V posttest (74.7° ± 10.0°) was greater than the PNF-V pretest (57.4° ± 10.4°), and the SS posttest (67.0° ± 10.7°) was greater than the SS pretest (60.1° ± 9.4°). When comparing the posttest values, the PNF-V posttest was greater than the SS posttest. All 3 stretches (PNF, PNF-V, and SS) resulted in acute increases in glenohumeral internal rotation in individuals presenting with GIRD. The PNF-V stretch resulted in the greatest increase and would be the most clinically beneficial for patients with GIRD.

The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia.

PubMed

Melachuri, Samyuktha; Gandrud, Laura; Bostrom, Bruce

2014-06-01

Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia. We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing. Patients also received complex carbohydrates at bedtime. Switching 6-MP from evening to morning administration reduced 6MMP levels yet preserved adequate levels of the active metabolite red cell 6-thioguanine nucleotide (6TGN). All patients had decreased hypoglycemic events when changed from evening to morning dosing. Two patients showed a rebound in 6MMP levels with return of hypoglycemic symptoms. Both were then switched to twice daily 6-MP dosing with one having a decrease in 6MMP and hypoglycemic symptoms. High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration. © 2014 Wiley Periodicals, Inc.

Absolute Quantitation of Water and Metabolites in the Human Brain. II. Metabolite Concentrations

NASA Astrophysics Data System (ADS)

Kreis, R.; Ernst, T.; Ross, B. D.

A method for determining absolute metabolite concentrations with in vivo1H magnetic resonance spectroscopy is presented. Using the compartmentation model introduced in the preceding paper of this series ( J. Magn. Reson. B102, 1, 1993), it is possible to express NMR results in terms of most commonly used concentration units. The proposed scheme, involving the measurement of an external standard as well as of the localized water signal, is verified on cerebral spectra obtained from 22 subjects. Besides concentrations, longitudinal and transverse relaxation times are determined for parietal white and occipital gray matter. The determination of these quantities crucially depends on the analysis of the T2 signal decay as a function of echo time. The in vivo concentrations of the four metabolites N-acetyl aspartate, creatine plus phosphocreatine, choline, and myo-inositol are in good agreement with biochemical determinations performed in vitro. Two clinical examples emphasize the relevance of absolute quantitation in the investigation of human neuropathology and normal development.

The development of ultrashort acting neuromuscular relaxant tropane derivatives.

PubMed

Gyermek, Laszlo; Lee, Chingmuh

2009-03-01

There is a need for neuromuscular relaxant (NMR) agents that are of the "nondepolarizing type" and produce rapidly developing and short-lasting skeletal muscle relaxation in anesthesiology. Many efforts have been directed to produce such agents. Our research focused on the design, synthesis, and evaluation of numerous "bisquaternary" derivatives of the cyclic aminoalkanes: tropane and granatane. Through systematic "steric structure-activity relationship" studies, we arrived at some new bisquaternary tropine and granatanol diesters, which in laboratory studies appeared to be the fastest and shortest acting NMRs recognized so far. Their ultrashort duration action-mechanism was, however, linked to the formation of nephrotoxic metabolites, precluding further development. Even so, we believe that the scientific information gained from more than a thousand such agents, will be useful toward developing the "ideal," ultrashort-acting NMR that could be clinically successful without the use of "reversing" agents, at least until "new biotechnology" may solve all problematic aspects of "transient" muscle relaxation.

Serum Metabonomics of Mild Acute Pancreatitis.

PubMed

Xu, Hongmin; Zhang, Lei; Kang, Huan; Zhang, Jiandong; Liu, Jie; Liu, Shuye

2016-11-01

Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P < 0.05). Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course. © 2016 Wiley Periodicals, Inc.

Spectral analysis of the central nervous system effects of the relaxation response elicited by autogenic training.

PubMed

Jacobs, G D; Lubar, J F

1989-01-01

This study examined the effects of the relaxation response, elicited by autogenic training, on central nervous system (CNS) activity. We used computerized spectral analysis of EEG activity as a dependent measure. After baseline EEG data were obtained for all subjects, the experimental group practiced standard autogenic exercises for 15 experimental sessions with home practice. The control subjects received the same number of sessions under identical conditions, except that they listened to a pleasant radio show without home practice. Subjects were then posttested to assess the acute and chronic effects of autogenic training and the relaxation response on CNS activity. The results indicated significant acute effects differences between groups; the experimental group showed greater increases in theta and greater decreases in alpha percent total power. The results suggest that the relaxation response elicited by autogenic training produces significant acute changes in EEG activity and a characteristic spectral pattern; the results also suggest that focusing attention on a repetitive, internal stimulus is a key element in Benson's relaxation response model.

Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis.

PubMed

Ali, Niaz; Ahmed, Ghayour; Shah, Syed Wadood Ali; Shah, Ismail; Ghias, Mehreen; Khan, Imran

2011-10-24

Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD(50) value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC(50) value for brine shrimp cytotoxicity is 65.5 ± 7.28 (60.8- 69.4, n

Relaxation therapies for asthma: a systematic review

PubMed Central

Huntley, A; White, A; Ernst, E

2002-01-01

Background: Emotional stress can either precipitate or exacerbate both acute and chronic asthma. There is a large body of literature available on the use of relaxation techniques for the treatment of asthma symptoms. The aim of this systematic review was to determine if there is any evidence for or against the clinical efficacy of such interventions. Methods: Four independent literature searches were performed on Medline, Cochrane Library, CISCOM, and Embase. Only randomised clinical trials (RCTs) were included. There were no restrictions on the language of publication. The data from trials that statistically compared the treatment group with that of the control were extracted in a standardised predefined manner and assessed critically by two independent reviewers. Results: Fifteen trials were identified, of which nine compared the treatment group with the control group appropriately. Five RCTs tested progressive muscle relaxation or mental and muscular relaxation, two of which showed significant effects of therapy. One RCT investigating hypnotherapy, one of autogenic training, and two of biofeedback techniques revealed no therapeutic effects. Overall, the methodological quality of the studies was poor. Conclusions: There is a lack of evidence for the efficacy of relaxation therapies in the management of asthma. This deficiency is due to the poor methodology of the studies as well as the inherent problems of conducting such trials. There is some evidence that muscular relaxation improves lung function of patients with asthma but no evidence for any other relaxation technique. PMID:11828041

Relaxation therapies for asthma: a systematic review.

PubMed

Huntley, A; White, A R; Ernst, E

2002-02-01

Emotional stress can either precipitate or exacerbate both acute and chronic asthma. There is a large body of literature available on the use of relaxation techniques for the treatment of asthma symptoms. The aim of this systematic review was to determine if there is any evidence for or against the clinical efficacy of such interventions. Four independent literature searches were performed on Medline, Cochrane Library, CISCOM, and Embase. Only randomised clinical trials (RCTs) were included. There were no restrictions on the language of publication. The data from trials that statistically compared the treatment group with that of the control were extracted in a standardised predefined manner and assessed critically by two independent reviewers. Fifteen trials were identified, of which nine compared the treatment group with the control group appropriately. Five RCTs tested progressive muscle relaxation or mental and muscular relaxation, two of which showed significant effects of therapy. One RCT investigating hypnotherapy, one of autogenic training, and two of biofeedback techniques revealed no therapeutic effects. Overall, the methodological quality of the studies was poor. There is a lack of evidence for the efficacy of relaxation therapies in the management of asthma. This deficiency is due to the poor methodology of the studies as well as the inherent problems of conducting such trials. There is some evidence that muscular relaxation improves lung function of patients with asthma but no evidence for any other relaxation technique.

Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

PubMed

Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Kanno, Keiko; Watanabe, Kenya; Mashiko, Hirobumi; Niwa, Shin-Ichi

2012-09-01

In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

Preliminary effects of progressive muscle relaxation on cigarette craving and withdrawal symptoms in experienced smokers in acute cigarette abstinence: a randomized controlled trial.

PubMed

Limsanon, Thatsanee; Kalayasiri, Rasmon

2015-03-01

Cigarette craving usually occurs in conjunction with unpleasant feelings, including stress, as part of a withdrawal syndrome. Progressive muscle relaxation (PMR), a behavioral technique used to reduce stress by concentrating on achieving muscle relaxation, may reduce levels of cigarette craving and other substance-related negative feelings and withdrawal symptoms. Demographic and cigarette use data were collected from 32 experienced smokers at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Participants were asked to refrain from smoking for at least 3 hours before the visit (acute abstinence) and were randomly allocated to a 1-session PMR group (n =16) or a control activity group (e.g., reading newspaper, n =16). The intervention group was instructed to practice PMR individually in a quiet, private, air-conditioned room for about 20minutes. Craving, other substance-related feelings, and autonomic nervous responses (e.g., blood pressure and pulse rate) were assessed immediately before and after the 1-session intervention. There were no differences in demographics, cigarette use/dependence, and baseline craving characteristics between the PMR and control groups. However, the control group had higher levels of high and paranoia feeling, and pulse rate than the PMR group at baseline. After practicing PMR, but not after a control activity, smokers undergoing acute abstinence had significantly lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than at baseline. After controlling for baseline differences, abstaining smokers using PMR had lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than smokers who undertook a control activity. PMR significantly reduces cigarette craving, withdrawal symptoms, and blood pressure in smokers undergoing acute abstinence. PMR may be used as an adjunct to cigarette dependency treatments

The 1H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study

PubMed Central

Mason, Shayne; Mienie, Lodewyk J.; Wevers, Ron A.; Westerhuis, Johan A.

2018-01-01

Metabolomics studies of disease conditions related to chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways underlying the pathophysiology of alcoholism. The objective of the present study was to utilize proton nuclear magnetic resonance (1H-NMR) spectroscopy metabolomics to study the holistic metabolic consequences of acute alcohol consumption in humans. The experimental design was a cross-over intervention study which included a number of substances to be consumed—alcohol, a nicotinamide adenine dinucleotide (NAD) supplement, and a benzoic acid-containing flavoured water vehicle. The experimental subjects—24 healthy, moderate-drinking young men—each provided six hourly-collected urine samples for analysis. Complete data sets were obtained from 20 of the subjects and used for data generation, analysis and interpretation. The results from the NMR approach produced complex spectral data, which could be resolved sufficiently through the application of a combination of univariate and multivariate methods of statistical analysis. The metabolite profiles resulting from acute alcohol consumption indicated that alcohol-induced NAD+ depletion, and the production of an excessive amount of reducing equivalents, greatly perturbed the hepatocyte redox homeostasis, resulting in essentially three major metabolic disturbances—up-regulated lactic acid metabolism, down-regulated purine catabolism and osmoregulation. Of these, the urinary excretion of the osmolyte sorbitol proved to be novel, and suggests hepatocyte swelling due to ethanol influx following acute alcohol consumption. Time-dependent metabolomics investigations, using designed interventions, provide a way of interpreting the variation induced by the different factors of a designed experiment, thereby also giving methodological significance to this study. The outcomes of this approach have the potential to significantly advance our understanding of the serious impact of

Degradation in soil and water and ecotoxicity of rimsulfuron and its metabolites.

PubMed

Martins, J M; Chevre, N; Spack, L; Tarradellas, J; Mermoud, A

2001-11-01

The degradation and ecotoxicity of sulfonylurea herbicide rimsulfuron and its major metabolites were examined in batch samples of an alluvial sandy loam and in freshwater. An HPLC-DAD method was adapted to simultaneously identify and quantify rimsulfuron and its metabolites, which was successfully validated by GC-MS analysis. In aqueous solutions, pure rimsulfuron was rapidly hydrolyzed into metabolite 1 (N-(4,6-dimethoxypyrimidin-2-yl)-N-(3-(ethylsulfonyl)-2-pyridinylurea)), which itself was transformed into the more stable metabolite 2 (N-((3-(ethylsulfonyl)-2-pyridinyl)-4,6-dimethoxy-2-pyrimidineamine)), with half-life (t(1/2)) values of 2 and 2.5 days, respectively. Hydrolysis was instantaneous under alkaline conditions (pH = 10). In aqueous suspensions of the alluvial soil (pH = 8), formulated rimsulfuron had a half-life of 7 days, whereas that of metabolite 1 was similar to that in water (about 3.5 days). The degradation of the two major metabolites was also studied in soil suspensions with the pure compounds at concentrations ranging from 1 to 10 mg l(-1). The half-life of metabolite 1 ranged from 3.9 to 5 days, close to the previous values. Metabolite 2 was more persistent and its degradation is strongly dependent on the initial concentration (C0): half-life values ranged from 8.1 to 55 days at 2-10 mg l(-1), respectively. These values are higher than those determined from the kinetics of metabolite 1 transformation into metabolite 2 (t(1/2) = 8-19 days). The ecotoxicity of the three chemicals was evaluated through their effect on Daphnia magna and Vibrio fischeri (Microtox bioassay). No effect was observed on D. magna with 24 and 48 h acute toxicity tests. Similarly, no toxic effect was observed with the Microtox test for the three chemicals in the range of concentrations tested that included the field application dose. Thus, being of low persistence and lacking acute toxicity, these chemicals present a low environmental risk. However, chronic effects

Fast mapping of the T2 relaxation time of cerebral metabolites using proton echo-planar spectroscopic imaging (PEPSI).

PubMed

Tsai, Shang-Yueh; Posse, Stefan; Lin, Yi-Ru; Ko, Cheng-Wen; Otazo, Ricardo; Chung, Hsiao-Wen; Lin, Fa-Hsuan

2007-05-01

Metabolite T2 is necessary for accurate quantification of the absolute concentration of metabolites using long-echo-time (TE) acquisition schemes. However, lengthy data acquisition times pose a major challenge to mapping metabolite T2. In this study we used proton echo-planar spectroscopic imaging (PEPSI) at 3T to obtain fast T2 maps of three major cerebral metabolites: N-acetyl-aspartate (NAA), creatine (Cre), and choline (Cho). We showed that PEPSI spectra matched T2 values obtained using single-voxel spectroscopy (SVS). Data acquisition for 2D metabolite maps with a voxel volume of 0.95 ml (32 x 32 image matrix) can be completed in 25 min using five TEs and eight averages. A sufficient spectral signal-to-noise ratio (SNR) for T2 estimation was validated by high Pearson's correlation coefficients between logarithmic MR signals and TEs (R2 = 0.98, 0.97, and 0.95 for NAA, Cre, and Cho, respectively). In agreement with previous studies, we found that the T2 values of NAA, but not Cre and Cho, were significantly different between gray matter (GM) and white matter (WM; P < 0.001). The difference between the T2 estimates of the PEPSI and SVS scans was less than 9%. Consistent spatial distributions of T2 were found in six healthy subjects, and disagreement among subjects was less than 10%. In summary, the PEPSI technique is a robust method to obtain fast mapping of metabolite T2. (c) 2007 Wiley-Liss, Inc.

RELAX: detecting relaxed selection in a phylogenetic framework.

PubMed

Wertheim, Joel O; Murrell, Ben; Smith, Martin D; Kosakovsky Pond, Sergei L; Scheffler, Konrad

2015-03-01

Relaxation of selective strength, manifested as a reduction in the efficiency or intensity of natural selection, can drive evolutionary innovation and presage lineage extinction or loss of function. Mechanisms through which selection can be relaxed range from the removal of an existing selective constraint to a reduction in effective population size. Standard methods for estimating the strength and extent of purifying or positive selection from molecular sequence data are not suitable for detecting relaxed selection, because they lack power and can mistake an increase in the intensity of positive selection for relaxation of both purifying and positive selection. Here, we present a general hypothesis testing framework (RELAX) for detecting relaxed selection in a codon-based phylogenetic framework. Given two subsets of branches in a phylogeny, RELAX can determine whether selective strength was relaxed or intensified in one of these subsets relative to the other. We establish the validity of our test via simulations and show that it can distinguish between increased positive selection and a relaxation of selective strength. We also demonstrate the power of RELAX in a variety of biological scenarios where relaxation of selection has been hypothesized or demonstrated previously. We find that obligate and facultative γ-proteobacteria endosymbionts of insects are under relaxed selection compared with their free-living relatives and obligate endosymbionts are under relaxed selection compared with facultative endosymbionts. Selective strength is also relaxed in asexual Daphnia pulex lineages, compared with sexual lineages. Endogenous, nonfunctional, bornavirus-like elements are found to be under relaxed selection compared with exogenous Borna viruses. Finally, selection on the short-wavelength sensitive, SWS1, opsin genes in echolocating and nonecholocating bats is relaxed only in lineages in which this gene underwent pseudogenization; however, selection on the functional

Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.).

PubMed

Teixeira, L L; Costa, G R; Dörr, F A; Ong, T P; Pinto, E; Lajolo, F M; Hassimotto, N M A

2017-06-21

The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively. According to pharmacokinetic parameters, the subjects were divided into two distinct groups, high and low urinary metabolite excretors. The pool of polyphenol metabolites found in urine samples showed a significant inhibition of cell proliferation and G2/M cell cycle arrest in MDA-MB-231 cells. Our findings demonstrate the large interindividual variability concerning the polyphenol metabolism, which possibly could reflect in health promotion.

Relaxation effect of abacavir on rat basilar arteries.

PubMed

Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

2015-01-01

The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction

Thiopurine methyltransferase genotype–phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia

PubMed Central

Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

2013-01-01

Aims In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype–genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. Methods We measured TPMT (activity, as units ml−1 packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 108 RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Results Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P < 0.0001). At diagnosis genotype–phenotype was discordant. During chemotherapy the overall concordance was 92%, but this fell to 55% in the intermediate activity cohort (45% had wild-type genotypes). For both thiopurines TGN concentrations differed by TPMT status. For mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P < 0.0001), whilst median MeMPNs, products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. Conclusions In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. PMID:23252716

Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.

PubMed

Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

2013-07-01

In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. We measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P < 0.0001). At diagnosis genotype-phenotype was discordant. During chemotherapy the overall concordance was 92%, but this fell to 55% in the intermediate activity cohort (45% had wild-type genotypes). For both thiopurines TGN concentrations differed by TPMT status. For mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P < 0.0001), whilst median MeMPNs, products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Relaxation Assessment with Varied Structured Milieu (RELAX).

ERIC Educational Resources Information Center

Cassel, Russell N.; Cassel, Susie L.

1983-01-01

Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

Relaxation Training and Opioid Inhibition of Blood Pressure Response to Stress.

ERIC Educational Resources Information Center

McCubbin, James A.; And Others

1996-01-01

Sought to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Subjects were 32 young men with mildly elevated casual arterial pressure. Assessed opioid mechanisms by examining the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and…

Relaxation Effect of Abacavir on Rat Basilar Arteries

PubMed Central

Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

2015-01-01

Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may

Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia.

PubMed

Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas; Rosthøj, Susanne; Nersting, Jacob

2015-05-01

High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue to prevent toxicities, but myelosuppression can also be prevented by pre-HD-MTX 6MP dose reductions. Accordingly, we monitored pre-HD-MTX erythrocyte levels of methylated 6MP metabolites (Ery-MeMP) and of thioguanine nucleotides (Ery-6TGN) as well as DNA-incorporated thioguanine nucleotides (DNA-TGN) in circulating leucocytes to identify patients at highest risk of post-HD-MTX myelosuppression. In multiple linear regression analyses of neutrophil and thrombocyte nadir values (adjusted for gender, age, risk group and 6MP dose) after 48 HD-MTX courses in 17 childhood ALL patients on MTX/6MP maintenance therapy, the pre-HD-MTX DNA-TGN levels in neutrophils (P < 0.0001), Ery-MeMP (P < 0.0001) and Ery-6TGN (P = 0.01) levels were significant predictors of post-HD-MTX neutrophil nadirs, whereas Ery-MeMP (P < 0.0001) was the only predictor of post-HD-MTX thrombocyte nadir. In conclusion, pre-HD-MTX 6MP metabolite levels may be applicable for 6MP dose adjustments to prevent HD-MTX-induced myelosuppression.

Benzene: a case study in parent chemical and metabolite interactions.

PubMed

Medinsky, M A; Kenyon, E M; Schlosser, P M

1995-12-28

Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia and pancytopenia, and acute myelogenous leukemia. A combination of metabolites (hydroquinone and phenol for example) is apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus, the potential exists for competition among various enzymes for phenol. However, zonal localization of Phase I and Phase II enzymes in various regions of the liver acinus regulates this competition. Biologically-based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.

After stress comes relax(ation)

NASA Astrophysics Data System (ADS)

Isa, Lucio

2015-11-01

Viscoelastic materials take a finite time to relax and dissipate stress and this time scale is directly connected to the microstructure of the material itself. In their paper, Gomez-Solano and Bechinger (2015 New J. Phys. 17 103032) perform ‘miniaturized’ mechanical tests on a range of viscoelastic materials by dragging a micron-sized bead across them using optical tweezers. Upon switching off all the external forces, they watch the bead recoil to its original position and by tracking its motion they pinpoint the relaxation time of the material. These experiments open up a new range of possibilities to characterize stress relaxation at the microscale just by watching it.

Relaxation-Induced Anxiety: Paradoxical Anxiety Enhancement Due to Relaxation Training.

ERIC Educational Resources Information Center

Heide, Frederick J.; Borkovec, T. D.

1983-01-01

Documented relaxation-induced anxiety in 14 subjects suffering from tension who were given training in progressive relaxation and mantra meditation. Four of the subjects displayed clinical evidence of an anxiety reaction during a preliminary practice period. Progressive relaxation produced less evidence of relaxation-induced anxiety. (Author/JAC)

Acute changes in knee cartilage transverse relaxation time after running and bicycling.

PubMed

Gatti, Anthony A; Noseworthy, Michael D; Stratford, Paul W; Brenneman, Elora C; Totterman, Saara; Tamez-Peña, José; Maly, Monica R

2017-02-28

To compare the acute effect of running and bicycling of an equivalent cumulative load on knee cartilage composition and morphometry in healthy young men. A secondary analysis investigated the relationship between activity history and the change in cartilage composition after activity. In fifteen men (25.8±4.2 years), the vertical ground reaction force was measured to determine the cumulative load exposure of a 15-min run. The vertical pedal reaction force was recorded during bicycling to define the bicycling duration of an equivalent cumulative load. On separate visits that were spaced on average 17 days apart, participants completed these running and bicycling bouts. Mean cartilage transverse relaxation times (T 2 ) were determined for cartilage on the tibia and weight-bearing femur before and after each exercise. T 2 was measured using a multi-echo spin-echo sequence and 3T MRI. Cartilage of the weight bearing femur and tibia was segmented using a highly-automated segmentation algorithm. Activity history was captured using the International Physical Activity Questionnaire. The response of T 2 to bicycling and running was different (p=0.019; mean T 2 : pre-running=34.27ms, pre-bicycling=32.93ms, post-running=31.82ms, post-bicycling=32.36ms). While bicycling produced no change (-1.7%, p=0.300), running shortened T 2 (-7.1%, p<0.001). Greater activity history predicted smaller changes in tibial, but not femoral, T 2 . Changes in knee cartilage vary based on activity type, independent of total load exposure, in healthy young men. Smaller changes in T 2 were observed after bicycling relative to running. Activity history was inversely related to tibial T 2 , suggesting cartilage conditioning. Copyright © 2017 Elsevier Ltd. All rights reserved.

The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors.

PubMed

Cunha, J F; Campestrini, F D; Calixto, J B; Scremin, A; Paulino, N

2001-03-01

We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC(50) values of 18 microM and E(max) of 100% (N = 10) or 20 microM and E(max) of 92% (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 +/- 7.0, 43 +/- 3.9 and 78 +/- 5.6%) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 microM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 microM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 +/- 12%. Glibenclamide (1 or 3 microM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K(+) channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 microM), a selective blocker of the large-conductance Ca(2+)-activated K(+) channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N(G)-nitroarginine (100 microM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 microM, while methylene blue (10 or 30 microM) or ODQ (1 microM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-(P)-Cl-Phe(6),Leu(17

Changes in MR Relaxation Times of the Meniscus With Acute Loading: An In Vivo Pilot Study in Knee Osteoarthritis

PubMed Central

Subburaj, Karupppasamy; Souza, Richard B.; Wyman, Bradley T.; Le Graverand-Gastineau, Marie-Pierre Hellio; Li, Xiaojuan; Link, Thomas M.; Majumdar, Sharmila

2014-01-01

Purpose To prospectively evaluate changes in T1ρ and T2 relaxation times in the meniscal body with acute loading using MRI in osteoarthritic knees and to compare these findings with those of age-matched healthy controls. Materials and Methods Female subjects above 40 years of age with (N1 = 20) and without osteoarthritis (OA) (N2 = 10) were imaged on a 3 Tesla MR scanner using a custom made loading device. MR images were acquired, with the knee flexed at 20°, with and without a compressive load of 50% of the subject's bodyweight. The subjects were categorized based on the radiographic evidence of OA. Three different zones (outer, middle, and inner) of meniscus body were defined (each occupying 1/3rd the width). After adjusting for age and body mass index in the general linear regression model, repeated measures analysis of variance was used to detect significant differences in T1ρ and T2 with and without loading. Results In the unloaded condition, the average T1ρ and T2 times were elevated in the outer and middle zones of the medial meniscus in OA subjects compared with the controls. In the loaded condition, T1ρ and T2 times of the outer zone of the medial meniscus was significantly elevated in OA subjects compared with controls. Finally the change (from unloaded to loaded) was significantly higher in controls than OA subjects (15.1% versus 8.3%; P = 0.039 for ΔT1ρ, and 11.5% versus 6.9%, P = 0.049 for ΔT2). Conclusion These findings suggest that while the OA process appears to affect the relaxation times of all regions within the meniscus, it may affect some regions sooner or to a greater degree. Furthermore, the differences in the change in relaxation times between unloaded and loaded conditions may reveal evidence about load transmission failure of the outer zone of the medial meniscus in subjects with knee OA. It is possible that these metrics (ΔT1ρ and ΔT2) may be valuable as an early biomechanical biomarker, which could be used to predict load

Yoga Nidra relaxation increases heart rate variability and is unaffected by a prior bout of Hatha yoga.

PubMed

Markil, Nina; Whitehurst, Michael; Jacobs, Patrick L; Zoeller, Robert F

2012-10-01

The measurement of heart rate variability (HRV) is often applied as an index of autonomic nervous system (ANS) balance and, therefore, myocardial stability. Previous studies have suggested that relaxation or mind-body exercise can influence ANS balance positively as measured by HRV but may act via different mechanisms. No studies, to the authors' knowledge, have examined the acute response in HRV to interventions combining relaxation and mind-body exercise. The objective of this study was to compare the acute HRV responses to Yoga Nidra relaxation alone versus Yoga Nidra relaxation preceded by Hatha yoga. This was a randomized counter-balanced trial. The trial was conducted in a university exercise physiology laboratory. Subjects included 20 women and men (29.15±6.98 years of age, with a range of 18-47 years). Participants completed a yoga plus relaxation (YR) session and a relaxation only (R) session. The YR condition produced significant changes from baseline in heart rate (HR; beats per minute [bpm], p<0.001) and indices of HRV: R-R (ms, p<0.001), pNN50 (%, p=0.009), low frequency (LF; %, p=0.008) and high frequency (HF; %, p=0.035). The R condition produced significant changes from baseline in heart rate (bpm, p<0.001) as well as indices of HRV: R-R (ms, p<0.001), HF (ms(2), p=0.004), LF (%, p=0.005), HF (%, p=0.008) and LF:HF ratio (%, p=0.008). There were no significant differences between conditions at baseline nor for the changes from baseline for any of the variables. These changes demonstrate a favorable shift in autonomic balance to the parasympathetic branch of the ANS for both conditions, and that Yoga Nidra relaxation produces favorable changes in measures of HRV whether alone or preceded by a bout of Hatha yoga.

Assessment of mercaptopurine (6MP) metabolites and 6MP metabolic key-enzymes in childhood acute lymphoblastic leukemia.

PubMed

Wojtuszkiewicz, Anna; Barcelos, Ana; Dubbelman, Boas; De Abreu, Ronney; Brouwer, Connie; Bökkerink, Jos P; de Haas, Valerie; de Groot-Kruseman, Hester; Jansen, Gerrit; Kaspers, Gertjan L; Cloos, Jacqueline; Peters, G J

2014-01-01

Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this pathway still remains unclear. This study attempted to determine which components of 6MP metabolism in leukemic blasts and red blood cells are important for 6MP's sensitivity and toxicity. In addition, changes in the enzymatic activities and metabolite levels during the treatment were analyzed. In a cohort (N=236) of pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S-methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of selected enzymes and levels of 6MP derivatives were measured at various time points during the course of therapy. The data obtained and the toxicity related parameters available for these patients were correlated with each other. We found several interesting relations, including high concentrations of two active forms of 6MP--TGN and meTIN--showing a trend toward association with better in vitro antileukemic effect of 6MP. High concentrations of TGN and elevated activity of HGPRT were found to be significantly associated with grade III/IV leucopenia. However, a lot of data of enzymatic activities and metabolite concentrations as well as clinical toxicity were missing, thereby limiting the number of assessed relations. Therefore, although a complex study of 6MP metabolism in ALL patients is feasible, it warrants more robust and strict data collection in order to be able to draw more reliable conclusions.

Breathing and Relaxation

MedlinePlus

... Programs Health Information Doctors & Departments Clinical Research & Science Education & Training Home Health Insights Stress & Relaxation Breathing and Relaxation Breathing and Relaxation Make ...

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.

1986-05-01

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM (/sup 14/C)GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentrationmore » was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM (/sup 14/C)GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST« less

Differentiable McCormick relaxations

DOE PAGES

Khan, Kamil A.; Watson, Harry A. J.; Barton, Paul I.

2016-05-27

McCormick's classical relaxation technique constructs closed-form convex and concave relaxations of compositions of simple intrinsic functions. These relaxations have several properties which make them useful for lower bounding problems in global optimization: they can be evaluated automatically, accurately, and computationally inexpensively, and they converge rapidly to the relaxed function as the underlying domain is reduced in size. They may also be adapted to yield relaxations of certain implicit functions and differential equation solutions. However, McCormick's relaxations may be nonsmooth, and this nonsmoothness can create theoretical and computational obstacles when relaxations are to be deployed. This article presents a continuously differentiablemore » variant of McCormick's original relaxations in the multivariate McCormick framework of Tsoukalas and Mitsos. Gradients of the new differentiable relaxations may be computed efficiently using the standard forward or reverse modes of automatic differentiation. Furthermore, extensions to differentiable relaxations of implicit functions and solutions of parametric ordinary differential equations are discussed. A C++ implementation based on the library MC++ is described and applied to a case study in nonsmooth nonconvex optimization.« less

Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

PubMed

Buness, Andreas; Roth, Adrian; Herrmann, Annika; Schmitz, Oliver; Kamp, Hennicke; Busch, Kristina; Suter, Laura

2014-01-01

Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI) using transcriptomics, metabolite profiling (metabolomics) and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine), classical clinical chemistry markers like AST (aspartate aminotransferase), ALT (alanine aminotransferase), and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1) and Egr1 (early growth response protein 1). The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

The effect of relaxation therapy on autonomic functioning, symptoms and daily functioning, in patients with chronic fatigue syndrome or fibromyalgia: a systematic review.

PubMed

Meeus, Mira; Nijs, Jo; Vanderheiden, Tanja; Baert, Isabel; Descheemaeker, Filip; Struyf, Filip

2015-03-01

To establish the effects of relaxation therapy on autonomic function, pain, fatigue and daily functioning in patients with chronic fatigue syndrome or fibromyalgia. A systematic literature study was performed. Using specific keywords related to fibromyalgia or chronic fatigue syndrome and relaxation therapy, the electronic databases PubMed and Web of Science were searched. Included articles were assessed for their risk of bias and relevant information regarding relaxation was extracted. The review was conducted and reported according to the PRISMA-statement. Thirteen randomized clinical trials of sufficient quality were included, resulting in a total of 650 fibromyalgia patients (11 studies) and 88 chronic fatigue syndrome patients (3 studies). None of the studies reported effects on autonomic function. Six studies reported the effect of guided imagery on pain and daily functioning in fibromyalgia. The acute effect of a single session of guided imagery was studied in two studies and seems beneficial for pain relief. For other relaxation techniques (eg. muscle relaxation, autogenic training) no conclusive evidence was found for the effect on pain and functioning in fibromyalgia patients comparison to multimodal treatment programs. For fatigue a multimodal approach seemed better than relaxation, as shown in the sole three studies on chronic fatigue syndrome patients. There is moderate evidence for the acute effect of guided imagery on pain, although the content of the visualization is a matter of debate. Other relaxation formats and the effects on functionality and autonomic function require further study. © The Author(s) 2014.

Acute effects of a guided relaxation routine (body scan) on tobacco withdrawal symptoms and cravings in abstinent smokers.

PubMed

Cropley, Mark; Ussher, Michael; Charitou, Elli

2007-06-01

To examine the acute effects of a guided relaxation routine (body scan) on desire to smoke and tobacco withdrawal symptoms in overnight abstinent smokers. Experimental. Thirty individuals reporting to smoke 10 or more cigarettes daily for at least 3 years. Participants were assigned randomly to complete a 10-minute body scan (experimental group n = 15) or listen to a natural history passage for 10 minutes (control group n = 15). Ratings of strength of desire to smoke and smoking withdrawal symptoms were assessed at baseline, immediately after the interventions, and 5, 10 and 15 minutes post-intervention. There was a significant group x time interaction for strength of desire to smoke. The mean desire to smoke rating was significantly lower in the body scan group relative to the control group immediately after the intervention, and 5 minutes post-intervention. The body scan group also reported lower ratings of irritability, tension and restlessness, relative to the controls. A brief body scan intervention reduces strength of desire to smoke and some tobacco withdrawal symptoms in temporarily abstaining smokers. The body scan may be beneficial as a technique for managing cigarette cravings and withdrawal.

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil.

PubMed

Phelps, Laura E; Peuler, Jacob D

2010-01-01

Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARalpha). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR alpha may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50-400 microM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 microM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or

How does a clinical trial fit into the real world? The RELAX-AHF study population into the EAHFE registry.

PubMed

Miró, Òscar; Gil, Víctor; Müller, Christian; Mebazaa, Alexander; Bueno, Héctor; Martín-Sánchez, Francisco Javier; Herrero, Pablo; Jacob, Javier; Llorens, Pere

2015-10-01

To test how accurate the recently published RELAX-AHF trial was in recruiting real-world patients with acute-decompensated heart failure (ADHF). We compared clinical and outcome data of patients receiving serelaxin in the RELAX-AHF trial (RELAX group, n = 581) with patients included in the EAHFE registry [5497 ADHF from 29 Spanish emergency departments (EDs)]. The EAHFE registry was split into two groups: EAHFE-non-RELAX (patients not fulfilling the RELAX-AHF inclusion criteria; n = 3205, 58.3 %) and EAHFE-RELAX A (patients fulfilling RELAX-AHF inclusion criteria; n = 2292, 41.7 %). The latter group was further refined by also applying exclusion criteria (EAHFE-RELAX B; n = 964, 17.4 %). Both EAHFE-RELAX groups differed from the EAHFE-non-RELAX group in multiple aspects, with the lower the proportion of patients with implantable cardiac defibrillator and with pulmonary diseases the greater the differences found. The RELAX group, compared with the EAHFE-RELAX groups, significantly included fewer females, younger patients, less in NYHA class I/II, less with implantable cardiac defibrillator and on beta-blocker treatment, and patients had lower systolic blood pressure and cardiac and respiratory rates at ED arrival. The EAHFE-RELAX groups had a significantly lower all-cause mortality than EAHFE-non-RELAX group, and qualitative analysis suggested that EAHFE-RELAX groups had a higher mortality than the RELAX group. Patients included in the RELAX-AHF trial showed unanticipated differences when compared with a population from the EAHFE registry fulfilling very similar inclusion and exclusion criteria.

Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls.

PubMed

Coppieters, Iris; Cagnie, Barbara; Nijs, Jo; van Oosterwijck, Jessica; Danneels, Lieven; De Pauw, Robby; Meeus, Mira

2016-03-01

Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. A randomized crossover design was employed. The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies. A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with

Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites.

PubMed

Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N; Nersting, Jacob; Albertsen, Birgitte K; Wehner, Peder S; Rosthøj, Steen; Lähteenmäki, Päivi M; Nilsson, Daniel; Nystad, Tove A; Grell, Kathrine; Frandsen, Thomas L; Schmiegelow, Kjeld

2017-09-01

Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy. In children with ALL treated in Denmark according to the NOPHO ALL2008 protocol, we investigated the risk of SOS during methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy that included PEG-asparaginase until week 33 (randomized to two- vs. six-week intervals), as well as alternating high-dose MTX or vincristine/dexamethasone pulses every four weeks. Among 130 children receiving PEG-asparaginase biweekly, 29 developed SOS (≥2 criteria: hyperbilirubinemia, hepatomegaly, ascites, weight gain ≥2.5%, unexplained thrombocytopenia <75 × 10 9 l -1 ) at a median of 30 days (interquartile range [IQR]: 17-66) into maintenance (cumulative incidence: 27%). SOS cases fulfilling one, two, or three Ponte di Legno criteria were classified as possible (n = 2), probable (n = 8), or verified (n = 19) SOS, respectively. Twenty-six cases (90%) occurred during PEG-asparaginase treatment, including 21 (81%) within 14 days from the last chemotherapy pulse compared with the subsequent 14 days (P = 0.0025). Cytotoxic 6MP metabolites were significantly higher on PEG-asparaginase compared to after its discontinuation. Time-dependent Cox regression analysis showed increased SOS hazard ratio (HR) for erythrocyte levels of methylated 6MP metabolites (HR: 1.09 per 1,000 nmol/mmol hemoglobin increase, 95% confidence interval: 1.05-1.14). Six-week PEG-asparaginase intervals significantly reduced SOS-specific hazards (P < 0.01). PEG-asparaginase increases cytotoxic 6MP metabolite levels and

Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

PubMed

Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

2017-01-01

The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

PubMed Central

Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

2017-01-01

The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension. PMID:28507519

Isolation, synthesis, and pharmacology of metabolites of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone.

PubMed

Schwan, T J; Ellis, K O; Wessels, F L; Pugh, D; Bell, R

1980-10-01

The metabolism of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone, an antianxiety/antidepressant agent, in dogs is reported. Two metabolites, 3-[1-(3,4-dichlorobenzyl)-1-ureido]propanoic acid and 1-(3,4-dichlorobenzyl)uracil, were isolated, characterized, and synthesized. Neither metabolite was acutely toxic, and they did not exhibit antidepressant or antianxiety/anticonvulsant activity.

In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard.

PubMed

Christiansen, P; Henriksen, O; Stubgaard, M; Gideon, P; Larsson, H B

1993-01-01

The reliability of absolute quantification of average metabolite concentrations in the human brain in vivo by 1H-MRS using the fully relaxed water signal as an internal standard was tested in a number of in vitro as well as in vivo measurements. The experiments were carried out on a SIEMENS HELICON SP 63/84 wholebody MR-scanner operating at 1.5 T using a STEAM sequence. In vitro studies indicate a very high correlation between metabolite signals (area under peaks) and concentration, R = 0.99 as well as between metabolite signals and the volume of the selected voxel, R = 1.00. The error in quantification of N-acetyl aspartate (NAA) concentration was about 1-2 mM (6-12%). Also in vivo a good linearity between water signal and selected voxel size was seen. The same was true for the studied metabolites, N-acetyl aspartate (NAA), creatine/phosphocreatine (Cr/PCr), and choline (Cho). Calculated average concentrations of NAA, Cr/PCr, and Cho in the occipital lobe of the brain in five healthy volunteers were (mean +/- 1 SD) 11.6 +/- 1.3 mM, 7.6 +/- 1.4 mM, and 1.7 +/- 0.5 mM. The results indicate that the method presented offers reasonable estimation of metabolite concentrations in the brain in vivo and therefore is useful in clinical research.

Effects of progressive relaxation and classical music on measurements of attention, relaxation, and stress responses.

PubMed

Scheufele, P M

2000-04-01

The present experiment examined relaxation using different experimental conditions to test whether the effects of individual elements of relaxation could be measured, whether specific effects were revealed, or whether relaxation resulted from a generalized "relaxation response." Sixty-seven normal, male volunteers were exposed to a stress manipulation and then to one of two relaxation (Progressive Relaxation, Music) or control (Attention Control, Silence) conditions. Measurements of attention, relaxation, and stress responses were obtained during each phase of the experiment. All four groups exhibited similar performance on behavioral measures of attention that suggested a reduction in physiological arousal following their relaxation or control condition, as well as a decreased heart rate. Progressive Relaxation, however, resulted in the greatest effects on behavioral and self-report measures of relaxation, suggesting that cognitive cues provided by stress management techniques contribute to relaxation.

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

PubMed Central

Nascimento, Alvaro F. S.; Mazzeti, Ana Lia; Marques, Luiz F.; Gonçalves, Karolina R.; Mota, Ludmilla W. R.; Diniz, Lívia de F.; Caldas, Ivo S.; Talvani, André; Shackleford, David M.; Koltun, Maria; Saunders, Jessica; White, Karen L.; Scandale, Ivan; Charman, Susan A.; Chatelain, Eric

2014-01-01

This study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma cruzi were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole. PMID:24841257

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

PubMed

Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

2015-12-25

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Capturing molecular multimode relaxation processes in excitable gases based on decomposition of acoustic relaxation spectra

NASA Astrophysics Data System (ADS)

Zhu, Ming; Liu, Tingting; Wang, Shu; Zhang, Kesheng

2017-08-01

Existing two-frequency reconstructive methods can only capture primary (single) molecular relaxation processes in excitable gases. In this paper, we present a reconstructive method based on the novel decomposition of frequency-dependent acoustic relaxation spectra to capture the entire molecular multimode relaxation process. This decomposition of acoustic relaxation spectra is developed from the frequency-dependent effective specific heat, indicating that a multi-relaxation process is the sum of the interior single-relaxation processes. Based on this decomposition, we can reconstruct the entire multi-relaxation process by capturing the relaxation times and relaxation strengths of N interior single-relaxation processes, using the measurements of acoustic absorption and sound speed at 2N frequencies. Experimental data for the gas mixtures CO2-N2 and CO2-O2 validate our decomposition and reconstruction approach.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

PubMed

Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

2018-03-01

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ACUTE ORAL ADMINISTRATION OF ARSENATE

EPA Science Inventory

ABSTRACT The relationship of exposure dose and tissue concentration of parent chemical and metabolites is a critical issue in cases where toxicity may be mediated by a metabolite or parent chemical and metabolite acting together. This has emerged as an issue for inorganic ars...

Relation between Direct Observation of Relaxation and Self-Reported Mindfulness and Relaxation States

ERIC Educational Resources Information Center

Hites, Lacey S.; Lundervold, Duane A.

2013-01-01

Forty-four individuals, 18-47 (MN 21.8, SD 5.63) years of age, took part in a study examining the magnitude and direction of the relationship between self-report and direct observation measures of relaxation and mindfulness. The Behavioral Relaxation Scale (BRS), a valid direct observation measure of relaxation, was used to assess relaxed behavior…

Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice.

PubMed

Kubo, Hisako; Hoshi, Masato; Mouri, Akihiro; Tashita, Chieko; Yamamoto, Yasuko; Nabeshima, Toshitaka; Saito, Kuniaki

2017-01-01

Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO -/- mice and KMO +/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80 + cells in KMO -/- mice was suppressed compared with those in KMO +/+ mice. KMO -/- mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO -/- mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Structural Relaxation of Vit4Amorphous Alloy by the Enthalpy Relaxation

NASA Astrophysics Data System (ADS)

O'Reilly, James; Hammond, Vincent

2002-03-01

The structural relaxation of an amorphous alloy designated Vit4 has been investigated as a function of thermal history using differential scanning calorimetry. Results indicate that the width of the glass transition region is approximately 30 °C, which is broader than molecular or polymeric glasses but similar to inorganic glasses. The broad transition implies a large distribution of relaxation times, a low activation energy, or a combination of these effects. The Tool-Narayanaswamy model for structural relaxation has been used to analyze the change in fictive temperature that occurs for a series of cooling rates. The activation energy calculated from these data the is 187 kJ/mol, a value that is low compared to other glasses. Using optimization programs, the other relaxation parameters, the characteristic relaxation time, the non-linearity parameter, x, and the fractional exponent of distribution of relaxation times, b, were determined from the experimental specific heat curves. Although the parameters were in good agreement with values typical of other glassy materials, there appears to be less correlation between them than is observed in molecular and polymeric glasses. The results obtained in this study indicate that the structural relaxation of Vit 4 is similar to other glasses except for a low activation energy with high glass transition. This could be due to a low free volume or configurational entropy. The width of the glass transition could result from a large distribution of relaxation times or a low activation energy. The exponent of the distribution of relaxation times, b, is 0.45±0.1 and the non-linearity parameter, x =0.5±0.2. The structural relaxation of Vit 4 is dominated by a low activation energy which is related to the atomic jump motion of hard spheres. The DCp at Tg should be 11.7 J/mol. deg per bead according to Wunderlich’s rule. This means that the change in Cp at Tg in Vit4 can be accounted for by one bead although there are five metal

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

PubMed

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H; Valcour, Victor

2012-01-01

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.

PubMed

Gerová, M; Török, J

2004-01-01

The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.

Urinary metabolite levels and symptoms in Filipino workers using organic solvents.

PubMed

Cucueco, M T; Espinosa, N C; Villanueva, M B; Castro, F T; Sison, S Y; Ortega, V S; Hisanaga, N

1993-01-01

To compare symptoms with urinary metabolite levels, 900 workers from 7 organic solvent-using industries were studied. Urinary metabolites were determined using a high performance liquid chromatograph. Urinary hippuric acid concentrations exceeding the reference value (2.5 g/g creatinine) were found in 78 (8.7%) workers. However, only 3 (0.3%) and 1 (0.1%) of the participants exceeded the reference value for mandelic (0.8 g/g creatinine) and total methylhippuric acid (1.5 g/g creatinine), respectively. The sum of the values of the ratio of measured urinary metabolite concentration to the corresponding ACGIH's biological exposure indices (BEI) [(HA/BEI of HA + MHA/BEI of MHA + MA/BEI of MA)] exceeded 1.0 in 166 (18.4%) workers. Majority of them were from the footwear manufacturing industry (63/129 or 49.2%). Questionnaire interviews were also administered to determine the prevalence of symptoms while at work (acute symptoms) or within the past 6 months (chronic symptoms). Urinary metabolite levels of individual and mixed solvents were compared with the symptoms of all workers. Analysis using Spearman's rank correlation showed in workers whose urinary hippuric acid exceeded 3.75 g/g creatine (1.5 x BEI), significant correlation between their hippuric acid levels and subjective complaints. Workers whose sum of the values of the ratio of measured urinary metabolite concentration to corresponding BEI exceeded 1.5 were selected and comparing this level with their symptoms, significant correlation was also noted in some complaints.

Mozart versus new age music: relaxation states, stress, and ABC relaxation theory.

PubMed

Smith, Jonathan C; Joyce, Carol A

2004-01-01

Smith's (2001) Attentional Behavioral Cognitive (ABC) relaxation theory proposes that all approaches to relaxation (including music) have the potential for evoking one or more of 15 factor-analytically derived relaxation states, or "R-States" (Sleepiness, Disengagement, Rested / Refreshed, Energized, Physical Relaxation, At Ease/Peace, Joy, Mental Quiet, Childlike Innocence, Thankfulness and Love, Mystery, Awe and Wonder, Prayerfulness, Timeless/Boundless/Infinite, and Aware). The present study investigated R-States and stress symptom-patterns associated with listening to Mozart versus New Age music. Students (N = 63) were divided into three relaxation groups based on previously determined preferences. Fourteen listened to a 28-minute tape recording of Mozart's Eine Kleine Nachtmusik and 14 listened to a 28-minute tape of Steven Halpern's New Age Serenity Suite. Others (n = 35) did not want music and instead chose a set of popular recreational magazines. Participants engaged in their relaxation activity at home for three consecutive days for 28 minutes a session. Before and after each session, each person completed the Smith Relaxation States Inventory (Smith, 2001), a comprehensive questionnaire tapping 15 R-States as well as the stress states of somatic stress, worry, and negative emotion. Results revealed no differences at Session 1. At Session 2, those who listened to Mozart reported higher levels of At Ease/Peace and lower levels of Negative Emotion. Pronounced differences emerged at Session 3. Mozart listeners uniquely reported substantially higher levels of Mental Quiet, Awe and Wonder, and Mystery. Mozart listeners reported higher levels, and New Age listeners slightly elevated levels, of At Ease/Peace and Rested/Refreshed. Both Mozart and New Age listeners reported higher levels of Thankfulness and Love. In summary, those who listened to Mozart's Eine Kleine Nachtmusik reported more psychological relaxation and less stress than either those who listened to

Equivalent Relaxations of Optimal Power Flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bose, S; Low, SH; Teeraratkul, T

2015-03-01

Several convex relaxations of the optimal power flow (OPF) problem have recently been developed using both bus injection models and branch flow models. In this paper, we prove relations among three convex relaxations: a semidefinite relaxation that computes a full matrix, a chordal relaxation based on a chordal extension of the network graph, and a second-order cone relaxation that computes the smallest partial matrix. We prove a bijection between the feasible sets of the OPF in the bus injection model and the branch flow model, establishing the equivalence of these two models and their second-order cone relaxations. Our results implymore » that, for radial networks, all these relaxations are equivalent and one should always solve the second-order cone relaxation. For mesh networks, the semidefinite relaxation and the chordal relaxation are equally tight and both are strictly tighter than the second-order cone relaxation. Therefore, for mesh networks, one should either solve the chordal relaxation or the SOCP relaxation, trading off tightness and the required computational effort. Simulations are used to illustrate these results.« less

Parasympathomimetic effect of shilajit accounts for relaxation of rat corpus cavernosum.

PubMed

Kaur, Sarabjeet; Kumar, Pravin; Kumar, Deo; Kharya, M D; Singh, Nityanand

2013-03-01

Previous studies have reported an enhancement of central cholinergic signal cascade by shilajit. For the present study, it was hypothesized that parasympathomimetic effect of shilajit accounting for relaxation of rat corpus cavernosum may be one of the major mechanisms attributing to its traditional role as an aphrodisiac. To test this hypothesis, the acute peripheral effect of standard acetylcholine (ACh), shilajit, and their combination was evaluated on cardiorespiratory parameters such as mean arterial blood pressure (MABP), heart rate (HR), respiratory rate (RR), and neuromuscular transmission (NMT). Furthermore, in vitro effect of standard ACh, shilajit, and their combination was tested on the rat corpus cavernosum. Six groups were used for the in vivo study (N = 5): Group I (control-saline), Group II (ACh), Group III (Sh), Group IV (Sh followed by ACh), Group V (Atropine followed by ACh), and Group VI (Atropine followed by Sh). The in vitro study included four groups: Group I (control-saline), Group II (ACh), Group III (Sh), and Group IV (Sh followed by ACh). The results of the in vivo study confirmed the peripheral parasympathomimetic effect of shilajit (400 µg/mL). The in vitro results revealed that shilajit (400 and 800 µg/mL) relaxed cavernous strips' concentration dependently and enhanced ACh-mediated relaxations. The peripheral parasympathomimetic effects of shilajit were confirmed by blockade of shilajit-induced relaxations (in vitro) and shilajit-induced lowering of MABP and HR (in vivo) by atropine.

OCT-based approach to local relaxations discrimination from translational relaxation motions

NASA Astrophysics Data System (ADS)

Matveev, Lev A.; Matveyev, Alexandr L.; Gubarkova, Ekaterina V.; Gelikonov, Grigory V.; Sirotkina, Marina A.; Kiseleva, Elena B.; Gelikonov, Valentin M.; Gladkova, Natalia D.; Vitkin, Alex; Zaitsev, Vladimir Y.

2016-04-01

Multimodal optical coherence tomography (OCT) is an emerging tool for tissue state characterization. Optical coherence elastography (OCE) is an approach to mapping mechanical properties of tissue based on OCT. One of challenging problems in OCE is elimination of the influence of residual local tissue relaxation that complicates obtaining information on elastic properties of the tissue. Alternatively, parameters of local relaxation itself can be used as an additional informative characteristic for distinguishing the tissue in normal and pathological states over the OCT image area. Here we briefly present an OCT-based approach to evaluation of local relaxation processes in the tissue bulk after sudden unloading of its initial pre-compression. For extracting the local relaxation rate we evaluate temporal dependence of local strains that are mapped using our recently developed hybrid phase resolved/displacement-tracking (HPRDT) approach. This approach allows one to subtract the contribution of global displacements of scatterers in OCT scans and separate the temporal evolution of local strains. Using a sample excised from of a coronary arteria, we demonstrate that the observed relaxation of local strains can be reasonably fitted by an exponential law, which opens the possibility to characterize the tissue by a single relaxation time. The estimated local relaxation times are assumed to be related to local biologically-relevant processes inside the tissue, such as diffusion, leaking/draining of the fluids, local folding/unfolding of the fibers, etc. In general, studies of evolution of such features can provide new metrics for biologically-relevant changes in tissue, e.g., in the problems of treatment monitoring.

Sleep, Stress & Relaxation: Rejuvenate Body & Mind

Cancer.gov

Sleep, Stress & Relaxation: Rejuvenate Body & Mind; Relieve Stress; best ways to relieve stress; best way to relieve stress; different ways to relieve stress; does smoking relieve stress; does tobacco relieve stress; how can I relieve stress; how can you relieve stress; how do I relieve stress; reduce stress; does smoking reduce stress; how can I reduce stress; how to reduce stress; reduce stress; reduce stress levels; reducing stress; smoking reduce stress; smoking reduces stress; stress reducing techniques; techniques to reduce stress; stress relief; best stress relief; natural stress relief; need stress relief; relief for stress; relief from stress; relief of stress; smoking and stress relief; smoking for stress relief; smoking stress relief; deal with stress; dealing with stress; dealing with anger; dealing with stress; different ways of dealing with stress; help dealing with stress; how to deal with anger; how to deal with stress; how to deal with stress when quitting smoking; stress management; free stress management; how can you manage stress; how do you manage stress; how to manage stress; manage stress; management of stress; management stress; managing stress; strategies for managing stress; coping with stress; cope with stress; copeing with stress; coping and stress; coping skills for stress; coping strategies for stress; coping strategies with stress; coping strategy for stress; coping with stress; coping with stress and anxiety; emotional health; emotional health; emotional health article; emotional health articles; deep relaxation; deep breathing relaxation techniques; deep muscle relaxation; deep relaxation; deep relaxation meditation; deep relaxation technique; deep relaxation techniques; meditation exercises; mindful exercises; mindful meditation exercises; online relaxation exercises; relaxation breathing exercises; relaxation exercise; relaxation exercises; stress relaxation; methods of relaxation for stress; relax stress; relax techniques stress

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

PubMed Central

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

2012-01-01

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

PubMed Central

Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

2008-01-01

Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

PubMed

Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

2016-03-01

Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

The effects of progressive muscle relaxation and autogenic relaxation on young soccer players' mood states.

PubMed

Hashim, Hairul Anuar; Hanafi Ahmad Yusof, Hazwani

2011-06-01

This study was designed to compare the effects of two different relaxation techniques, namely progressive muscle relaxation (PMR) and autogenic relaxation (AGR) on moods of young soccer players. sixteen adolescent athletes (mean age: 14.1 ± 1.3) received either PMR or AGR training. Using Profile of Mood States- Adolescents, their mood states were measured one week before relaxation training, before the first relaxation session, and after the twelfth relaxation session. Mixed ANOVA revealed no significant interaction effects and no significant main effects in any of the subscales. However, significant main effects for testing sessions were found for confusion, depression, fatigue, and tension subscales. Post hoc tests revealed post-intervention reductions in the confusion, depression, fatigue, and tension subscale scores. These two relaxation techniques induce equivalent mood responses and may be used to regulate young soccer players' mood states.

Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods.

PubMed

Lloyd, Amanda J; Favé, Gaëlle; Beckmann, Manfred; Lin, Wanchang; Tailliart, Kathleen; Xie, Long; Mathers, John C; Draper, John

2011-10-01

The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context.

Acute effects of tea consumption on attention and mood.

PubMed

Einöther, Suzanne J; Martens, Vanessa E

2013-12-01

Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.

A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

PubMed Central

Everett, Jeremy R.

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field. PMID:25750701

A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

PubMed

Everett, Jeremy R

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

The Effects of Progressive Muscle Relaxation and Autogenic Relaxation on Young Soccer Players’ Mood States

PubMed Central

Hashim, Hairul Anuar; Hanafi@Ahmad Yusof, Hazwani

2011-01-01

Purpose This study was designed to compare the effects of two different relaxation techniques, namely progressive muscle relaxation (PMR) and autogenic relaxation (AGR) on moods of young soccer players. Methods Sixteen adolescent athletes (mean age: 14.1 ± 1.3) received either PMR or AGR training. Using Profile of Mood States- Adolescents, their mood states were measured one week before relaxation training, before the first relaxation session, and after the twelfth relaxation session. Results Mixed ANOVA revealed no significant interaction effects and no significant main effects in any of the subscales. However, significant main effects for testing sessions were found for confusion, depression, fatigue, and tension subscales. Post hoc tests revealed post-intervention reductions in the confusion, depression, fatigue, and tension subscale scores. Conclusion These two relaxation techniques induce equivalent mood responses and may be used to regulate young soccer players’ mood states. PMID:22375225

Tryptophan Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors.

PubMed

Badawy, Abdulla A-B; Bano, Samina

2016-01-01

Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureni-nase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynureninase activity from K and 3-HK. Trp (50 mg/kg) increased kynurenine metabolite concentrations and KAT from K, and exerted a temporary stimulation of TDO. The kynureninase inhibitors BSZ and CBD also inhibited KAT, but stimulated TDO. BSZ abolished or strongly inhibited the Trp-induced increases in liver Trp and kynurenine metabolites. The potential effects of these changes in conditions of immune activation, schizophrenia, and other disease states are discussed.

Distribution of grape seed flavanols and their metabolites in pregnant rats and their fetuses.

PubMed

Arola-Arnal, Anna; Oms-Oliu, Gemma; Crescenti, Anna; del Bas, Josep Maria; Ras, Maria Rosa; Arola, Lluís; Caimari, Antoni

2013-10-01

Polyphenols have been demonstrated to provide health benefits affecting cellular and physiological processes. This study aims to evaluate the bioavailability and distribution of grape seed flavanol compounds during pregnancy and whether fetuses could be exposed to these compounds. The distribution of flavanols and their metabolites in rat plasma, liver, white adipose tissue, brain, amniotic fluid, placenta, and fetuses after 1 and 2 h of an acute intake of a grape seed proanthocyanidin extract was examined by LC-ESI-TOF/MS. Flavanols and their metabolites were widely distributed in both pregnant and nonpregnant rat plasma and tissues. In liver, the conjugated forms of flavanols were less available in pregnant than nonpregnant rats. Flavanol metabolites were abundant in maternal placenta but detected at low levels in fetuses and amniotic fluid. Flavanol metabolization appears to be less active in the liver during pregnancy. Moreover, data indicated that transport across the placenta is not efficient and for flavanols and their metabolites, the placenta seems to act as a barrier. However, these compounds target the fetus and are excreted in the amniotic fluid. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation

PubMed Central

Lam, Maggie; Royce, Simon G.; Donovan, Chantal; Jelinic, Maria; Parry, Laura J.; Samuel, Chrishan S.; Bourke, Jane E.

2016-01-01

Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250–350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX) alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator) or β-adrenoceptor agonists (isoprenaline, salbutamol) were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor), L-NAME (nitric oxide synthase inhibitor), SQ22536 (adenylate cyclase inhibitor) and ODQ (guanylate cyclase inhibitor) were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone, and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in the airways was at higher levels in epithelium than smooth muscle. In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely

Serum Metabolic Profiling of Oocyst-Induced Toxoplasma gondii Acute and Chronic Infections in Mice Using Mass-Spectrometry

PubMed Central

Zhou, Chun-Xue; Cong, Wei; Chen, Xiao-Qing; He, Shen-Yi; Elsheikha, Hany M.; Zhu, Xing-Quan

2018-01-01

Toxoplasma gondii is an obligate intracellular parasite causing severe diseases in immunocompromised individuals and congenitally infected neonates, such as encephalitis and chorioretinitis. This study aimed to determine whether serum metabolic profiling can (i) identify metabolites associated with oocyst-induced T. gondii infection and (ii) detect systemic metabolic differences between T. gondii-infected mice and controls. We performed the first global metabolomics analysis of mice serum challenged with 100 sporulated T. gondii Pru oocysts (Genotype II). Sera from acutely infected mice (11 days post-infection, dpi), chronically infected mice (33 dpi) and control mice were collected and analyzed using LC-MS/MS platform. Following False Discovery Rate filtering, we identified 3871 and 2825 ions in ESI+ or ESI− mode, respectively. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) identified metabolomic profiles that clearly differentiated T. gondii-infected and -uninfected serum samples. Acute infection significantly influenced the serum metabolome. Our results identified common and uniquely perturbed metabolites and pathways. Acutely infected mice showed perturbations in metabolites associated with glycerophospholipid metabolism, biosynthesis of amino acid, and tyrosine metabolism. These findings demonstrated that acute T. gondii infection induces a global perturbation of mice serum metabolome, providing new insights into the mechanisms underlying systemic metabolic changes during early stage of T. gondii infection. PMID:29354104

Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats.

PubMed

Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

2014-01-01

The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. MDMA (1-20 mg·kg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg·kg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats

PubMed Central

Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

2014-01-01

BACKGROUND AND PURPOSE The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. EXPERIMENTAL APPROACH Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. KEY RESULTS MDMA (1–20 mg·kg−1) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1–10 mg·kg−1) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. CONCLUSIONS AND IMPLICATIONS Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. PMID:24328722

[Indications for relaxation in geriatrics].

PubMed

Richard, J; Picot, A; de Bus, P; Andreoli, A; Dalakaki, X

1975-11-01

On a three years base experience in the geriatiic department of Geneva's University Psychiatric Clinic the paper studies the problem of selecting aged patients to be treated by relaxation according to the method of J. De Ajuriaguerra et M. Cahen. Observations are presented in an attempt to define three main points: a) the role played by relaxation when there is an objective [corrected] impairment of the body's integrity; b) relaxation effect on aged persons neurotic states evolution; c) the reality of considering dementia as a counter-indication of relaxation therapy. These remarks complete those presented previously about the training of therapists in relaxation, the type of control to be organized for them and their patients, the technical management of the cure, the place of relaxation in the post graduate psychiatric training, the effects of the therapy on the patients human environnement behavior in and out of the hospital, the way body is perceived through relaxation by the aged patients and it's consequences on the adjustment of an aging person.

High and ultra-high resolution metabolite mapping of the human brain using 1H FID MRSI at 9.4T.

PubMed

Nassirpour, Sahar; Chang, Paul; Henning, Anke

2018-03-01

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique for mapping the spatial distribution of multiple metabolites in the human brain. These metabolite maps can be used as a diagnostic tool to gain insight into several biochemical processes and diseases in the brain. In comparison to lower field strengths, MRSI at ultra-high field strengths benefits from a higher signal to noise ratio (SNR) as well as higher chemical shift dispersion, and hence spectral resolution. This study combines the benefits of an ultra-high field magnet with the advantages of an ultra-short TE and TR single-slice FID-MRSI sequence (such as negligible J-evolution and loss of SNR due to T 2 relaxation effects) and presents the first metabolite maps acquired at 9.4T in the healthy human brain at both high (voxel size of 97.6µL) and ultra-high (voxel size of 24.4µL) spatial resolutions in a scan time of 11 and 46min respectively. In comparison to lower field strengths, more anatomically-detailed maps with higher SNR from a larger number of metabolites are shown. A total of 12 metabolites including glutamate (Glu), glutamine (Gln), N-acetyl-aspartyl-glutamate (NAAG), Gamma-aminobutyric acid (GABA) and glutathione (GSH) are reliably mapped. Comprehensive description of the methodology behind these maps is provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Melatonin metabolite, N(1)-acetyl-N(1)-formyl-5-methoxykynuramine (AFMK), attenuates acute pancreatitis in the rat: in vivo and in vitro studies.

PubMed

Jaworek, J; Szklarczyk, J; Bonior, J; Kot, M; Goralska, M; Pierzchalski, P; Reiter, R J; Czech, U; Tomaszewska, R

2016-06-01

Melatonin protects the pancreas from inflammation and free radical damage but the effect of the melatonin metabolite: N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on acute pancreatitis is unknown. This study assessed the effects of AFMK on acute pancreatitis (AP) in the rats in vivo and on pancreatic cell line AR42J in vitro. AFMK (5, 10 or 20 mg/kg) was given intraperitoneally to the rats 30 min prior to the induction of AP by subcutaneous caerulein infusion (25 μg/kg). Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue. Blood samples were taken for evaluation of amylase activity and TNF-α concentration. GPx, TNF-α, proapoptotic Bax protein, antiapoptotic Bcl-2 protein and the executor of apoptosis, caspase-3, were determined by Western blot in AR42J cells subjected to AFMK or to melatonin (both used at 10(-12), 10(-10), or 10(-8)M), without or with addition of caerulein (10(-8)M). AP was confirmed by histological examination and by serum increases of amylase and TNF-α (by 800% and 300%, respectively). In AP rats, pancreatic MDA + 4-HNE levels were increased by 300%, whereas GPx was reduced by 50%. AFMK significantly diminished histological manifestations of AP, decreased serum amylase activity and TNF-α concentrations, reduced MDA + 4-HNE levels and augmented GPx in the pancreas of AP rats. In AR42J cells, AFMK combined with caerulein markedly increased protein signals for GPx, Bax, caspase-3 and reduced these for TNF-α and Bcl-2. In conclusion, AFMK significantly attenuated acute pancreatitis in the rat. This may relate to the antioxidative and anti-inflammatory effects of this molecule and possibly to the stimulation of proapoptotic signal transduction pathway.

Time scales of relaxation dynamics during transient conditions in two-phase flow: RELAXATION DYNAMICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlüter, Steffen; Berg, Steffen; Li, Tianyi

2017-06-01

The relaxation dynamics toward a hydrostatic equilibrium after a change in phase saturation in porous media is governed by fluid reconfiguration at the pore scale. Little is known whether a hydrostatic equilibrium in which all interfaces come to rest is ever reached and which microscopic processes govern the time scales of relaxation. Here we apply fast synchrotron-based X-ray tomography (X-ray CT) to measure the slow relaxation dynamics of fluid interfaces in a glass bead pack after fast drainage of the sample. The relaxation of interfaces triggers internal redistribution of fluids, reduces the surface energy stored in the fluid interfaces, andmore » relaxes the contact angle toward the equilibrium value while the fluid topology remains unchanged. The equilibration of capillary pressures occurs in two stages: (i) a quick relaxation within seconds in which most of the pressure drop that built up during drainage is dissipated, a process that is to fast to be captured with fast X-ray CT, and (ii) a slow relaxation with characteristic time scales of 1–4 h which manifests itself as a spontaneous imbibition process that is well described by the Washburn equation for capillary rise in porous media. The slow relaxation implies that a hydrostatic equilibrium is hardly ever attained in practice when conducting two-phase experiments in which a flux boundary condition is changed from flow to no-flow. Implications for experiments with pressure boundary conditions are discussed.« less

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons.

PubMed

Song, Kyu-Ho; Baek, Hyeon-Man; Lee, Do-Wan; Choe, Bo-Young

2015-10-01

The aim of this study was to evaluate the transverse relaxation time of methylene resonance as compared to other lipid resonances. The examinations were performed using a 3.0 T scanner with a point-resolved spectroscopy (PRESS) sequence. Lipid relaxation time in a lipid phantom filled with canola oil was estimated with a repetition time (TR) of 6000ms and echo time (TE) of 40-550ms. For in vivo proton magnetic resonance spectroscopy ((1)H-MRS), eight male Sprague-Dawley rats were given free access to a normal-chow (NC) and another eight male Sprague-Dawley rats were given free access to a high-fat (HF) diet. Both groups drank water ad libitum. T2 measurements in the rats' livers were conducted at a fixed TR of 6000ms and TE of 40-220ms. Exponential curve fitting quality was calculated through the coefficients of determination (R(2)). Chemical analyses of the phantom and livers were not performed, but T2 decay curves were acquired. The T2 relaxation time of methylene resonance was estimated as follows: NC rats, 37.1±4.3ms; HF rats, 31.4±1.8ms (p<0.05). The extrapolated M0 values were higher in HF rats than in NC rats (p<0.005). This study of (1)H MRS led to sufficient spectral resolution and signal-to-noise ratio differences to characterize the T2 relaxation times of methylene resonance. (1)H MRS relaxation times may be useful for quantitative characterization of various liver diseases, including fatty liver disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Slow secondary relaxation in a free-energy landscape model for relaxation in glass-forming liquids

NASA Astrophysics Data System (ADS)

Diezemann, Gregor; Mohanty, Udayan; Oppenheim, Irwin

1999-02-01

Within the framework of a free-energy landscape model for the relaxation in supercooled liquids the primary (α) relaxation is modeled by transitions among different free-energy minima. The secondary (β) relaxation then corresponds to intraminima relaxation. We consider a simple model for the reorientational motions of the molecules associated with both processes and calculate the dielectric susceptibility as well as the spin-lattice relaxation times. The parameters of the model can be chosen in a way that both quantities show a behavior similar to that observed in experimental studies on supercooled liquids. In particular we find that it is not possible to obtain a crossing of the time scales associated with α and β relaxation. In our model these processes always merge at high temperatures and the α process remains above the merging temperature. The relation to other models is discussed.

Anomalous relaxation in fractal structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujiwara, S.; Yonezawa, F.

1995-03-01

For the purpose of studying some interesting properties of anomalous relaxation in fractal structures, we carry out Monte Carlo simulations of random walks on two-dimensional fractal structures (Sierpinski carpets with different cutouts and site-percolation clusters in a square lattice at the critical concentration). We find that the relaxation is of the Cole-Cole type [J. Chem. Phys. 9, 341 (1941)], which is one of the empirical laws of anomalous relaxation. Scaling properties are found in the relaxation function as well as in the particle density. We also find that, in strucures with almost the same fractal dimension, relaxation in structures withmore » dead ends is slower than that in structures without them. This paper ascertains that the essential aspects of the anomalous relaxation due to many-body effects can be explained in the framework of the one-body model.« less

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation.

PubMed

Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo

2017-03-01

Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic

Characterization of Microbial Dysbiosis and Metabolomic Changes in Dogs with Acute Diarrhea

PubMed Central

Guard, Blake C.; Barr, James W.; Reddivari, Lavanya; Klemashevich, Cory; Jayaraman, Arul; Steiner, Jörg M.; Vanamala, Jairam; Suchodolski, Jan S.

2015-01-01

Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, Faecalibacterium, and an unclassified genus within Ruminococcaceae were underrepresented, the genus Clostridium was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in Faecalibacterium (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states. PMID:26000959

Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea.

PubMed

Guard, Blake C; Barr, James W; Reddivari, Lavanya; Klemashevich, Cory; Jayaraman, Arul; Steiner, Jörg M; Vanamala, Jairam; Suchodolski, Jan S

2015-01-01

Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, Faecalibacterium, and an unclassified genus within Ruminococcaceae were underrepresented, the genus Clostridium was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in Faecalibacterium (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states.

TEACHING NEUROMUSCULAR RELAXATION.

ERIC Educational Resources Information Center

NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

PubMed

Michelet, Pierre; Carreira, Serge; Demoule, Alexandre; Amour, Julien; Langeron, Olivier; Riou, Bruno; Coirault, Catherine

2015-04-01

Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

A Comparison of Relaxation Strategies.

ERIC Educational Resources Information Center

Matthews, Doris B.

Some researchers argue that all relaxation techniques produce a single relaxation response while others support a specific-effects hypothesis which suggests that progressive relaxation affects the musculoskeletal system and that guided imagery affects cognitive changes. Autogenics is considered a technique which is both somatic and cognitive. This…

Activation of endogenous GABAA channels on airway smooth muscle potentiates isoproterenol-mediated relaxation.

PubMed

Gallos, George; Gleason, Neil R; Zhang, Yi; Pak, Sang-Woo; Sonett, J R; Yang, Jay; Emala, Charles W

2008-12-01

Reactive airway disease predisposes patients to episodes of acute smooth muscle mediated bronchoconstriction. We have for the first time recently demonstrated the expression and function of endogenous ionotropic GABA(A) channels on airway smooth muscle cells. We questioned whether endogenous GABA(A) channels on airway smooth muscle could augment beta-agonist-mediated relaxation. Guinea pig tracheal rings or human bronchial airway smooth muscles were equilibrated in organ baths with continuous digital tension recordings. After pretreatment with or without the selective GABA(A) antagonist gabazine (100 muM), airway muscle was contracted with acetylcholine or beta-ala neurokinin A, followed by relaxation induced by cumulatively increasing concentrations of isoproterenol (1 nM to 1 muM) in the absence or presence of the selective GABA(A) agonist muscimol (10-100 muM). In separate experiments, guinea pig tracheal rings were pretreated with the large conductance K(Ca) channel blocker iberiotoxin (100 nM) after an EC(50) contraction with acetylcholine but before cumulatively increasing concentrations of isoproterenol (1 nM to 1 uM) in the absence or presence of muscimol (100 uM). GABA(A) activation potentiated the relaxant effects of isoproterenol after an acetylcholine or tachykinin-induced contraction in guinea pig tracheal rings or an acetylcholine-induced contraction in human endobronchial smooth muscle. This muscimol-induced potentiation of relaxation was abolished by gabazine pretreatment but persisted after blockade of the maxi K(Ca) channel. Selective activation of endogenous GABA(A) receptors significantly augments beta-agonist-mediated relaxation of guinea pig and human airway smooth muscle, which may have important therapeutic implications for patients in severe bronchospasm.

Application of dried blood spot cards to determine olive oil phenols (hydroxytyrosol metabolites) in human blood.

PubMed

de Las Hazas, María Carmen López; Motilva, Maria José; Piñol, Carme; Macià, Alba

2016-10-01

In this study, a fast and simple blood sampling and sample pre-treatment method based on the use of the dried blood spot (DBS) cards and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for the quantification of olive oil phenolic metabolites in human blood was developed and validated. After validation, the method was applied to determine hydroxytyrosol metabolites in human blood samples after the acute intake of an olive oil phenolic extract. Using the FTA DMPK-A DBS card under optimum conditions, with 20µL as the blood solution volume, 100µL of methanol/Milli-Q water (50/50, v/v) as the extraction solvent and 7 disks punched out from the card, the main hydroxytyrosol metabolites (hydroxytyrosol-3-O-sulphate and hydroxytyrosol acetate sulphate) were identified and quantified. The developed methodology allowed detecting and quantifying the generated metabolites at low μM levels. The proposed method is a significant improvement over existing methods to determine phenolic metabolites circulating in blood and plasma samples, thus making blood sampling possible with the volunteer pricking their own finger, and the subsequent storage of the blood in the DBS cards prior to chromatographic analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.

PubMed

Ren, Xiaobin; Zhang, Mingzhu; Chen, Lingxiang; Zhang, Wanli; Huang, Yu; Luo, Huazhen; Li, Ling; He, Hongbing

2017-10-01

The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess anti‑inflammatory properties, however its mechanism of action remains unclear. It was previously reported that YNB ameliorated depression of arachidonic acid (AA) levels in a rat model of collagen-induced arthritis. In the current study, the capacity of YNB to ameliorate inflammation was compared in carrageenan‑induced and AA‑induced acute inflammation of the rat paw with celecoxib and mizolastine, respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2 (PLA2)/AA pathway (using reverse transcription‑quantitative polymerase chain reaction) and release of inflammatory lipid mediators (by ELISA) were investigated. Celecoxib ameliorated carrageenan‑induced paw edema, and mizolastine ameliorated AA‑induced rat paw edema. YNB alleviated paw edema and inhibited inflammatory cell infiltration in the two models. YNB inhibited production of 5‑LOX AA metabolite leukotriene B4 (LTB4), and suppressed expression of 5‑LOX, cytosolic PLA2 (cPLA2), 5‑LOX‑activating protein, and LTB4 receptor mRNA in the AA‑induced inflammation model (P<0.05). YNB Inhibited the production of the COX‑2 AA metabolite prostaglandin E2 (PGE2) and suppressed expression of COX‑2, cPLA2, PGE2 mRNA in the carrageenan‑induced inflammation mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm.

PubMed

Montaño, Luis M; Espinoza, Julia; Flores-Soto, Edgar; Chávez, Jaime; Perusquía, Mercedes

2014-07-01

Changes in the androgen levels in asthmatic men may be associated with the severity of asthma. Androgens induce a nongenomic relaxation in airway smooth muscle, but the underlying mechanisms remain unclear. The aim of this study was to investigate the potential bronchorelaxing action of testosterone (TES) and its metabolites (5α- and 5β-dihydrotestosterone (DHT). A preventive effect on ovalbumin (OVA)-induced bronchospasm was observed in sensitized guinea pigs for each androgen. Androgens were studied in response to bronchoconstrictors: carbachol (CCh) and KCl in isolated trachea rings with and without epithelium from non-sensitized and sensitized animals as well as on OVA-induced contraction. Androgens concentration-dependently abolished the contraction in response to CCh, KCl, and OVA. There were significant differences in the sensitivity to the relaxation induced by each androgen. 5β-DHT was more potent for relaxing KCl-induced contraction, while TES and 5α-DHT were more potent for CCh- and OVA-induced contraction. No differences were found in preparations with and without epithelium or in the presence of a nitric oxide (NO) synthase inhibitor or an inhibitor of K(+) channels. These data indicate the absence of involvement of the epithelium-, NO- and K(+) channels-dependent pathway in androgen-induced relaxation. However, in dissociated tracheal myocytes loaded with the calcium-binding fluorescent dye Fura -2, physiological concentrations of androgens decreased the KCl-induced [Ca(2+)]i increment. 5β-DHT was the most potent at decreasing KCl-induced [Ca(2+)]i increment and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca(2+) influx through L-type Ca(2+)channels but additional Ca(2+) entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action. © 2014 Society for Endocrinology.

Relaxation Dynamics in Heme Proteins.

NASA Astrophysics Data System (ADS)

Scholl, Reinhard Wilhelm

A protein molecule possesses many conformational substates that are likely arranged in a hierarchy consisting of a number of tiers. A hierarchical organization of conformational substates is expected to give rise to a multitude of nonequilibrium relaxation phenomena. If the temperature is lowered, transitions between substates of higher tiers are frozen out, and relaxation processes characteristic of lower tiers will dominate the observational time scale. This thesis addresses the following questions: (i) What is the energy landscape of a protein? How does the landscape depend on the environment such as pH and viscosity, and how can it be connected to specific structural parts? (ii) What relaxation phenomena can be observed in a protein? Which are protein specific, and which occur in other proteins? How does the environment influence relaxations? (iii) What functional form best describes relaxation functions? (iv) Can we connect the motions to specific structural parts of the protein molecule, and are these motions important for the function of the protein?. To this purpose, relaxation processes after a pressure change are studied in carbonmonoxy (CO) heme proteins (myoglobin-CO, substrate-bound and substrate-free cytochrome P450cam-CO, chloroperoxidase-CO, horseradish peroxidase -CO) between 150 K and 250 K using FTIR spectroscopy to monitor the CO bound to the heme iron. Two types of p -relaxation experiments are performed: p-release (200 to ~eq40 MPa) and p-jump (~eq40 to 200 MPa) experiments. Most of the relaxations fall into one of three groups and are characterized by (i) nonexponential time dependence and non-Arrhenius temperature dependence (FIM1( nu), FIM1(Gamma)); (ii) exponential time dependence and non-Arrhenius temperature dependence (FIM0(A_{i}to A_{j})); exponential time dependence and Arrhenius temperature dependence (FIMX( nu)). The influence of pH is studied in myoglobin-CO and shown to have a strong influence on the substate population of the

Data Normalization of (1)H NMR Metabolite Fingerprinting Data Sets in the Presence of Unbalanced Metabolite Regulation.

PubMed

Hochrein, Jochen; Zacharias, Helena U; Taruttis, Franziska; Samol, Claudia; Engelmann, Julia C; Spang, Rainer; Oefner, Peter J; Gronwald, Wolfram

2015-08-07

Data normalization is an essential step in NMR-based metabolomics. Conducted properly, it improves data quality and removes unwanted biases. The choice of the appropriate normalization method is critical and depends on the inherent properties of the data set in question. In particular, the presence of unbalanced metabolic regulation, where the different specimens and cohorts under investigation do not contain approximately equal shares of up- and down-regulated features, may strongly influence data normalization. Here, we demonstrate the suitability of the Shapiro-Wilk test to detect such unbalanced regulation. Next, employing a Latin-square design consisting of eight metabolites spiked into a urine specimen at eight different known concentrations, we show that commonly used normalization and scaling methods fail to retrieve true metabolite concentrations in the presence of increasing amounts of glucose added to simulate unbalanced regulation. However, by learning the normalization parameters on a subset of nonregulated features only, Linear Baseline Normalization, Probabilistic Quotient Normalization, and Variance Stabilization Normalization were found to account well for different dilutions of the samples without distorting the true spike-in levels even in the presence of marked unbalanced metabolic regulation. Finally, the methods described were applied successfully to a real world example of unbalanced regulation, namely, a set of plasma specimens collected from patients with and without acute kidney injury after cardiac surgery with cardiopulmonary bypass use.

Metabolomics and Its Application to Acute Lung Diseases

PubMed Central

Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

2016-01-01

Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

PubMed

Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

2017-03-01

Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping

Mitochondria control acute and chronic responses to hypoxia.

PubMed

McElroy, G S; Chandel, N S

2017-07-15

There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute increases in respiration triggered by the carotid body chemosensory cells, and chronic changes such as induction of red blood cell proliferation and angiogenesis by hypoxia inducible factor targets erythropoietin and vascular endothelial growth factor, respectively. Mitochondria account for the majority of oxygen consumption in the cell and have recently been appreciated to serve as signaling organelles required for the initiation or propagation of numerous homeostatic mechanisms. Mitochondria can influence cell signaling by production of reactive oxygen species and metabolites. Here we review recent evidence that mitochondrial signals can imitate acute and chronic hypoxia responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Chloride channel blockade relaxes airway smooth muscle and potentiates relaxation by β-agonists

PubMed Central

Yim, Peter; Rinderspacher, Alison; Fu, Xiao Wen; Zhang, Yi; Landry, Donald W.; Emala, Charles W.

2014-01-01

Severe bronchospasm refractory to β-agonists continues to cause significant morbidity and mortality in asthmatic patients. We questioned whether chloride channels/transporters are novel targets for the relaxation of airway smooth muscle (ASM). We have screened a library of compounds, derivatives of anthranilic and indanyloxyacetic acid, that were originally developed to antagonize chloride channels in the kidney. We hypothesized that members of this library would be novel calcium-activated chloride channel blockers for the airway. The initial screen of this compound library identified 4 of 20 compounds that relaxed a tetraethylammonium chloride-induced contraction in guinea pig tracheal rings. The two most effective compounds, compounds 1 and 13, were further studied for their potential to either prevent the initiation of or relax the maintenance phase of an acetylcholine (ACh)-induced contraction or to potentiate β-agonist-mediated relaxation. Both relaxed an established ACh-induced contraction in human and guinea pig ex vivo ASM. In contrast, the prevention of an ACh-induced contraction required copretreatment with the sodium-potassium-chloride cotransporter blocker bumetanide. The combination of compound 13 and bumetanide also potentiated relaxation by the β-agonist isoproterenol in guinea pig tracheal rings. Compounds 1 and 13 hyperpolarized the plasma cell membrane of human ASM cells and blocked spontaneous transient inward currents, a measure of chloride currents in these cells. These functional and electrophysiological data suggest that modulating ASM chloride flux is a novel therapeutic target in asthma and other bronchoconstrictive diseases. PMID:24879056

Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms.

PubMed

Shin, Hwa Kyoung; Salomone, Salvatore; Potts, E Michelle; Lee, Sae-Won; Millican, Eric; Noma, Kensuke; Huang, Paul L; Boas, David A; Liao, James K; Moskowitz, Michael A; Ayata, Cenk

2007-05-01

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.

Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis.

PubMed

Heijne, Wilbert H M; Lamers, Robert-Jan A N; van Bladeren, Peter J; Groten, John P; van Nesselrooij, Joop H J; van Ommen, Ben

2005-01-01

This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute hepatic centrilobular necrosis. Bromobenzene-induced lesions were only observed after treatment with the highest of 3 dose levels. Multivariate statistical analysis showed that metabolite profiles of blood plasma were largely different from controls when the rats were treated with bromobenzene, also at doses that did not elicit histopathological changes. Changes in levels of genes and metabolites were related to the degree of necrosis, providing putative novel markers of hepatotoxicity. Levels of endogenous metabolites like alanine, lactate, tyrosine and dimethylglycine differed in plasma from treated and control rats. The metabolite profiles of urine were found to be reflective of the exposure levels. This integrated analysis of hepatic transcriptomics and plasma metabolomics was able to more sensitively detect changes related to hepatotoxicity and discover novel markers. The relation between gene expression and metabolite levels was explored and additional insight in the role of various biological pathways in bromobenzene-induced hepatic necrosis was obtained, including the involvement of apoptosis and changes in glycolysis and amino acid metabolism. The complete Table 2 is available as a supplemental file online at http://taylorandfrancis.metapress.com/openurlasp?genre=journal&issn=0192-6233. To access the file, click on the issue link for 33(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries.

PubMed

Amemori, Hiroko; Maeda, Yoshinori; Torikai, Arisu; Nakashima, Mikio

2011-12-01

Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10(-6) to 3 × 10(-4) M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K(+) (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca(2+)-induced normal physiologic contraction.

Localized 2D COSY sequences: Method and experimental evaluation for a whole metabolite quantification approach

NASA Astrophysics Data System (ADS)

Martel, Dimitri; Tse Ve Koon, K.; Le Fur, Yann; Ratiney, Hélène

2015-11-01

Two-dimensional spectroscopy offers the possibility to unambiguously distinguish metabolites by spreading out the multiplet structure of J-coupled spin systems into a second dimension. Quantification methods that perform parametric fitting of the 2D MRS signal have recently been proposed for resolved PRESS (JPRESS) but not explicitly for Localized Correlation Spectroscopy (LCOSY). Here, through a whole metabolite quantification approach, correlation spectroscopy quantification performances are studied. The ability to quantify metabolite relaxation constant times is studied for three localized 2D MRS sequences (LCOSY, LCTCOSY and the JPRESS) in vitro on preclinical MR systems. The issues encountered during implementation and quantification strategies are discussed with the help of the Fisher matrix formalism. The described parameterized models enable the computation of the lower bound for error variance - generally known as the Cramér Rao bounds (CRBs), a standard of precision - on the parameters estimated from these 2D MRS signal fittings. LCOSY has a theoretical net signal loss of two per unit of acquisition time compared to JPRESS. A rapid analysis could point that the relative CRBs of LCOSY compared to JPRESS (expressed as a percentage of the concentration values) should be doubled but we show that this is not necessarily true. Finally, the LCOSY quantification procedure has been applied on data acquired in vivo on a mouse brain.

Relaxation System

NASA Technical Reports Server (NTRS)

1987-01-01

Environ Corporation's relaxation system is built around a body lounge, a kind of super easy chair that incorporates sensory devices. Computer controlled enclosure provides filtered ionized air to create a feeling of invigoration, enhanced by mood changing aromas. Occupant is also surrounded by multidimensional audio and the lighting is programmed to change colors, patterns, and intensity periodically. These and other sensory stimulators are designed to provide an environment in which the learning process is stimulated, because research has proven that while an individual is in a deep state of relaxation, the mind is more receptive to new information.

Uninvolved versus target muscle contraction during contract: relax proprioceptive neuromuscular facilitation stretching.

PubMed

Azevedo, Daniel Camara; Melo, Raphael Marques; Alves Corrêa, Ricardo Vidal; Chalmers, Gordon

2011-08-01

The purpose of this study was to compare the acute effect of the contract-relax (CR) stretching technique on knee active range of motion (ROM) using target muscle contraction or an uninvolved muscle contraction. pre-test post-test control experimental design. Clinical research laboratory. Sixty healthy men were randomly assigned to one of three groups. The Contract-Relax group (CR) performed a traditional hamstring CR stretch, the Modified Contract-Relax group (MCR) performed hamstring CR stretching using contraction of an uninvolved muscle distant from the target muscle, and the Control group (CG) did not stretch. Active knee extension test was performed before and after the stretching procedure. Two-way between-within analysis of variance (ANOVA) results showed a significant interaction between group and pre-test to post-test (p < 0.001). Post-hoc examination of individual groups showed no significant change in ROM for the CG (0.8°, p = 0.084), and a significant moderate increase in ROM for both the CR (7.0°, p < 0.001) and MCR (7.0°, p < 0.001) groups. ROM gain following a CR PNF procedure is the same whether the target stretching muscle is contracted, or an uninvolved muscle is contracted. Copyright © 2011 Elsevier Ltd. All rights reserved.

Patulin and secondary metabolite production by marine-derived Penicillium strains.

PubMed

Vansteelandt, Marieke; Kerzaon, Isabelle; Blanchet, Elodie; Fossi Tankoua, Olivia; Robiou Du Pont, Thibaut; Joubert, Yolaine; Monteau, Fabrice; Le Bizec, Bruno; Frisvad, Jens C; Pouchus, Yves François; Grovel, Olivier

2012-09-01

Genus Penicillium represents an important fungal group regarding to its mycotoxin production. Secondary metabolomes of eight marine-derived strains belonging to subgenera Furcatum and Penicillium were investigated using dereplication by liquid chromatography (LC)-Diode Array Detector (DAD)-mass spectrometry (MS)/MS. Each strain was grown on six different culture media to enhance the number of observable metabolites. Thirty-two secondary metabolites were detected in crude extracts with twenty first observations for studied species. Patulin, a major mycotoxin, was classically detected in extracts of Penicillium expansum, and was also isolated from Penicillium antarcticum cultures, whose secondary metabolome is still to be done. These detections constituted the first descriptions of patulin in marine strains of Penicillium, highlighting the risk for shellfish and their consumers due to the presence of these fungi in shellfish farming areas. Patulin induced acute neurotoxicity on Diptera larvae, indicating the interest of this bioassay as an additional tool for detection of this major mycotoxin in crude extracts. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

PubMed

Sanchon-Lopez, Beatriz; Everett, Jeremy R

2016-09-02

A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

[Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

2015-01-01

Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

Idiosyncratic reality claims, relaxation dispositions, and ABC relaxation theory: happiness, literal christianity, miraculous powers, metaphysics, and the paranormal.

PubMed

Smith, Jonathan C; Karmin, Aaron D

2002-12-01

This study examined idiosyncratic reality claims, that is, irrational or paranormal beliefs often claimed to enhance relaxation and happiness and reduce stress. The Smith Idiosyncratic Reality Claims Inventory and the Smith Relaxation Dispositions Inventory (which measures relaxation and stress dispositions, or enduring states of mind frequently associated with relaxation or stress) were given to 310 junior college student volunteers. Principal components factor analysis with varimax rotation identified five idiosyncratic reality claim factors: belief in Literal Christianity; Magic; Space Aliens: After Death experiences; and Miraculous Powers of Meditation, Prayer, and Belief. No factor correlated with increased relaxation dispositions Peace, Energy, or Joy, or reduced dispositional somatic stress, worry, or negative emotion on the Smith Relaxation Dispositions Inventory. It was concluded that idiosyncratic reality claims may not be associated with reported relaxation, happiness, or stress. In contrast, previous research strongly supported self-affirming beliefs with few paranormal assumptions display such an association.

Urinary Metabolite Profiles May be Predictive of Cognitive Performance Under Conditions of Acute Sleep Deprivation

DTIC Science & Technology

2016-01-01

temporal changes in urinary metabolite profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by...profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by cognitive assessments as having a high...field studies and would have little useful application in occupational or military operational environments. Addition - ally, their usefulness is

The relationships between suggestibility, influenceability, and relaxability.

PubMed

Polczyk, Romuald; Frey, Olga; Szpitalak, Malwina

2013-01-01

This research explores the relationships between relaxability and various aspects of suggestibility and influenceability. The Jacobson Progressive Muscle Relaxation procedure was used to induce relaxation. Tests of direct suggestibility, relating to the susceptibility of overt suggestions, and indirect suggestibility, referring to indirect hidden influence, as well as self-description questionnaires on suggestibility and the tendency to comply were used. Thayer's Activation-Deactivation Adjective Check List, measuring various kinds of activation and used as a pre- and posttest, determined the efficacy of the relaxation procedure. Indirect, direct, and self-measured suggestibility proved to be positively related to the ability to relax, measured by Thayer's subscales relating to emotions. Compliance was not related to relaxability. The results are discussed in terms of the aspects of relaxation training connected with suggestibility.

Engineering Microbial Metabolite Dynamics and Heterogeneity.

PubMed

Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

2017-10-01

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rindler fluid with weak momentum relaxation

NASA Astrophysics Data System (ADS)

Khimphun, Sunly; Lee, Bum-Hoon; Park, Chanyong; Zhang, Yun-Long

2018-01-01

We realize the weak momentum relaxation in Rindler fluid, which lives on the time-like cutoff surface in an accelerating frame of flat spacetime. The translational invariance is broken by massless scalar fields with weak strength. Both of the Ward identity and the momentum relaxation rate of Rindler fluid are obtained, with higher order correction in terms of the strength of momentum relaxation. The Rindler fluid with momentum relaxation could also be approached through the near horizon limit of cutoff AdS fluid with momentum relaxation, which lives on a finite time-like cutoff surface in Anti-de Sitter(AdS) spacetime, and further could be connected with the holographic conformal fluid living on AdS boundary at infinity. Thus, in the holographic Wilson renormalization group flow of the fluid/gravity correspondence with momentum relaxation, the Rindler fluid can be considered as the Infrared Radiation(IR) fixed point, and the holographic conformal fluid plays the role of the ultraviolet(UV) fixed point.

Virodhamine relaxes the human pulmonary artery through the endothelial cannabinoid receptor and indirectly through a COX product

PubMed Central

Kozłowska, H; Baranowska, M; Schlicker, E; Kozłowski, M; Laudañski, J; Malinowska, B

2008-01-01

Background and purpose: The endocannabinoid virodhamine is a partial agonist at the cannabinoid CB1 receptor and a full agonist at the CB2 receptor, and relaxes rat mesenteric arteries through endothelial cannabinoid receptors. Its concentration in the periphery exceeds that of the endocannabinoid anandamide. Here, we examined the influence of virodhamine on the human pulmonary artery. Experimental approach: Isolated human pulmonary arteries were obtained during resections for lung carcinoma. Vasorelaxant effects of virodhamine were examined on endothelium-intact vessels precontracted with 5-HT or KCl. Key results: Virodhamine, unlike WIN 55,212-2, relaxed 5-HT-precontracted vessels concentration dependently. The effect of virodhamine was reduced by endothelium denudation, two antagonists of the endothelial cannabinoid receptor, cannabidiol and O-1918, and a high concentration of the CB1 receptor antagonist rimonabant (5 μM), but only slightly attenuated by the NOS inhibitor L-NAME and not affected by a lower concentration of rimonabant (100 nM) or by the CB2 and vanilloid receptor antagonists SR 144528 and capsazepine, respectively. The COX inhibitor indomethacin and the fatty acid amide hydrolase inhibitor URB597 and combined administration of selective blockers of small (apamin) and intermediate and large (charybdotoxin) conductance Ca2+-activated K+ channels attenuated virodhamine-induced relaxation. The vasorelaxant potency of virodhamine was lower in KCl- than in 5-HT-precontracted preparations. Conclusions and implications: Virodhamine relaxes the human pulmonary artery through the putative endothelial cannabinoid receptor and indirectly through a COX-derived vasorelaxant prostanoid formed from the virodhamine metabolite, arachidonic acid. One or both of these mechanisms may stimulate vasorelaxant Ca2+-activated K+ channels. PMID:18806815

The Effects of Suggestibility on Relaxation.

ERIC Educational Resources Information Center

Rickard, Henry C.; And Others

1985-01-01

Selected undergraduates (N=32) on the basis of Creative Imagination Scale scores and randomly assigned high and low suggestibility subjects to progressive relaxation (PR) and suggestions of relaxation (SR) training modes. Results revealed a significant pre-post relaxation effect, and main efffects for both suggestibility and training mode. (NRB)

Relaxation processes in disaccharide sugar glasses

NASA Astrophysics Data System (ADS)

Hwang, Yoon-Hwae; Kwon, Hyun-Joung; Seo, Jeong-Ah; Shin, Dong-Myeong; Ha, Ji-Hye; Kim, Hyung-Kook

2013-02-01

We represented relaxation processes of disaccharide sugars (anhydrous trehalose and maltose) in supercooled and glassy states by using several spectroscopy techniques which include a broadband dielectric loss spectroscopy, photon correlation spectroscopy and X-ray diffraction (Retvield analysis) methods which are powerful tools to measure the dynamics in glass forming materials. In a dielectric loss spectroscopy study, we found that anhydrous trehalose and maltose glasses have an extra relaxation process besides α-, JG β- and γ-relaxations which could be related to a unique property of glycoside bond in disaccharides. In photon correlation spectroscopy study, we found an interesting compressed exponential relaxation at temperatures above 140°C. The q-1 dependence of its relaxation time corresponds to an ultraslow ballistic motion due to the local structure rearrangements. In the same temperature range, we found the glycosidic bond structure changes in trehalose molecule from the Raman and the Retvield X-ray diffraction measurements indicating that the observed compressed exponential relaxation in supercooled liquid trehalose could be resulted in the glycosidic bond structure change. Therefore, the overall results from this study might support the fact that the superior bioprotection ability of disaccharide sugar glasses might originate from this unique relaxation process of glycosidic bond.

Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A

PubMed Central

Zhou, Junxuan; Zhang, Cong

2018-01-01

Ellagitannins in Phyllanthus emblica L. (emblic leafflower fruits) have been thought of as the beneficial constituents for ameliorating endocrinal and metabolic diseases including diabetes. However, the effect of emblic leafflower fruits on diabetic vascular complications involved in ellagitannin-derived urolithin metabolites is still rare. In this study, acetylcholine-induced endothelium-independent relaxation in aortas was facilitated upon emblic leafflower fruit consumption in the single dose streptozotocin-induced hyperglycemic rats. Emblic leafflower fruit consumption also suppressed the phosphorylation of Akt (Thr308) in the hyperglycemic aortas. More importantly, urolithin A (UroA) and its derived phase II metabolites were identified as the metabolites upon emblic leafflower fruit consumption by HPLC-ESI-Q-TOF-MS. Moreover, UroA reduced the protein expressions of phosphor-Akt (Thr308) and β-catenin in a high glucose-induced A7r5 vascular smooth muscle cell proliferation model. Furthermore, accumulation of β-catenin protein and activation of Wnt signaling in LiCl-triggered A7r5 cells were also ameliorated by UroA treatment. In conclusion, our data demonstrate that emblic leafflower fruit consumption facilitates the vascular function in hyperglycemic rats by regulating Akt/β-catenin signaling, and the effects are potentially mediated by the ellagitannin metabolite urolithin A. PMID:29692859

Tyrosol and its metabolites as antioxidative and anti-inflammatory molecules in human endothelial cells.

PubMed

Muriana, Francisco J G; Montserrat-de la Paz, Sergio; Lucas, Ricardo; Bermudez, Beatriz; Jaramillo, Sara; Morales, Juan C; Abia, Rocio; Lopez, Sergio

2017-08-01

Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective.

Relaxation mode analysis and Markov state relaxation mode analysis for chignolin in aqueous solution near a transition temperature

NASA Astrophysics Data System (ADS)

Mitsutake, Ayori; Takano, Hiroshi

2015-09-01

It is important to extract reaction coordinates or order parameters from protein simulations in order to investigate the local minimum-energy states and the transitions between them. The most popular method to obtain such data is principal component analysis, which extracts modes of large conformational fluctuations around an average structure. We recently applied relaxation mode analysis for protein systems, which approximately estimates the slow relaxation modes and times from a simulation and enables investigations of the dynamic properties underlying the structural fluctuations of proteins. In this study, we apply this relaxation mode analysis to extract reaction coordinates for a system in which there are large conformational changes such as those commonly observed in protein folding/unfolding. We performed a 750-ns simulation of chignolin protein near its folding transition temperature and observed many transitions between the most stable, misfolded, intermediate, and unfolded states. We then applied principal component analysis and relaxation mode analysis to the system. In the relaxation mode analysis, we could automatically extract good reaction coordinates. The free-energy surfaces provide a clearer understanding of the transitions not only between local minimum-energy states but also between the folded and unfolded states, even though the simulation involved large conformational changes. Moreover, we propose a new analysis method called Markov state relaxation mode analysis. We applied the new method to states with slow relaxation, which are defined by the free-energy surface obtained in the relaxation mode analysis. Finally, the relaxation times of the states obtained with a simple Markov state model and the proposed Markov state relaxation mode analysis are compared and discussed.

Relaxation Time of High-Density Amorphous Ice

NASA Astrophysics Data System (ADS)

Handle, Philip H.; Seidl, Markus; Loerting, Thomas

2012-06-01

Amorphous water plays a fundamental role in astrophysics, cryoelectron microscopy, hydration of matter, and our understanding of anomalous liquid water properties. Yet, the characteristics of the relaxation processes taking place in high-density amorphous ice (HDA) are unknown. We here reveal that the relaxation processes in HDA at 110-135 K at 0.1-0.2 GPa are of collective and global nature, resembling the alpha relaxation in glassy material. Measured relaxation times suggest liquid-like relaxation characteristics in the vicinity of the crystallization temperature at 145 K. By carefully relaxing pressurized HDA for several hours at 135 K, we produce a state that is closer to the ideal glass state than all HDA states discussed so far in literature.

Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure.

PubMed

Aouey, Bakhta; Derbali, Mohamed; Chtourou, Yassine; Bouchard, Michèle; Khabir, Abdelmajid; Fetoui, Hamadi

2017-02-01

Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1 mg/kg bw of LTC for 7, 30, 45, and 60 days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as

Relaxation in x-space magnetic particle imaging.

PubMed

Croft, Laura R; Goodwill, Patrick W; Conolly, Steven M

2012-12-01

Magnetic particle imaging (MPI) is a new imaging modality that noninvasively images the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIOs). MPI has demonstrated high contrast and zero attenuation with depth, and MPI promises superior safety compared to current angiography methods, X-ray, computed tomography, and magnetic resonance imaging angiography. Nanoparticle relaxation can delay the SPIO magnetization, and in this work we investigate the open problem of the role relaxation plays in MPI scanning and its effect on the image. We begin by amending the x-space theory of MPI to include nanoparticle relaxation effects. We then validate the amended theory with experiments from a Berkeley x-space relaxometer and a Berkeley x-space projection MPI scanner. Our theory and experimental data indicate that relaxation reduces SNR and asymmetrically blurs the image in the scanning direction. While relaxation effects can have deleterious effects on the MPI scan, we show theoretically and experimentally that x-space reconstruction remains robust in the presence of relaxation. Furthermore, the role of relaxation in x-space theory provides guidance as we develop methods to minimize relaxation-induced blurring. This will be an important future area of research for the MPI community.

Hair Dye and Hair Relaxers

MedlinePlus

... For Consumers Consumer Information by Audience For Women Hair Dye and Hair Relaxers Share Tweet Linkedin Pin it More sharing ... products. If you have a bad reaction to hair dyes and relaxers, you should: Stop using the ...

Acute histopathological changes produced by Penicillium aurantiogriseum nephrotoxin in the rat.

PubMed Central

Adatia, R.; Heaton, J. M.; Macgeorge, K. M.; Mantle, P. G.

1991-01-01

Shredded wheat moulded by an isolate of Penicillium aurantiogriseum elicited progressive histopathological changes at the rat renal cortico-medullary junction during 5 days of dosing, when incorporated into diet as a 20% component. The changes of acute tubular necrosis and regeneration were seen in the P3 segment of the nephron. In rats exposed to contaminated diet for 5 days the histopathological changes regressed in severity by about one-half within a further 4 days on normal diet and by 7 days the tubular epithelium was nearly normal. A partially purified fraction of an alcohol extract, selected by preparative high-voltage electrophoresis and anion exchange and notably rich in amino-compounds, was typically nephrotoxic when given in diet over 4 days. Acute marked tubular necrosis also occurred when the same fraction was given intraperitoneally over a similar period. The acute histological changes provide a rapid bioassay for this Penicillium nephrotoxicity and facilitate the search for the toxic metabolite(s). The cumulative expression of necrosis and repair over only a few days in tubular epithelium suggests that chronic exposure will elicit a more complex pathology which might serve as an experimental model for the idiopathic Balkan endemic nephropathy. Images Fig. 1 p51-a Fig. 2 PMID:1888665

Effect of Heat Stress on Concentrations of Faecal Cortisol Metabolites in Dairy Cows.

PubMed

Rees, A; Fischer-Tenhagen, C; Heuwieser, W

2016-06-01

The negative impact of heat stress on health and productivity of dairy cows is well known. Heat stress can be quantified with the temperature-humidity index (THI) and is defined as a THI ≥ 72. Additionally, animal welfare is affected in cows living under heat stress conditions. Finding a way to quantify heat stress in dairy cows has been of increasing interest over the past decades. Therefore, the objective of this study was to evaluate concentrations of faecal glucocorticoid metabolites [i.e. 11,17-dioxoandrostanes (11,17-DOA)] as an indirect stress parameter in dairy cows without heat stress (DOA 0), with heat stress on a single day (acute heat stress, DOA 1) or with more than a single day of heat stress (chronic heat stress, DOA 2). Cows were housed in five farms under moderate European climates. Two statistical approaches (approach 1 and approach 2) were assessed. Using approach 1, concentrations of faecal 11,17-DOA were compared among DOA 0, DOA 1 and DOA 2 samples regardless of their origin (i.e. cow, unpaired comparison with a one-way anova). Using approach 2, a cow was considered as its own control; that is 11,17-DOA was treated as a cow-specific factor and only paired samples were included in the analysis for this approach (paired comparison with t-tests). In approach 1 (p = 0.006) and approach 2 (p = 0.038), 11,17-DOA values of cows under acute heat stress were higher compared to those of cows without heat stress. Our results also indicate that acute heat stress has to be considered as a confounder in studies measuring faecal glucocorticoid metabolites in cows to evaluate other stressful situations. © 2016 Blackwell Verlag GmbH.

Metabolomics for secondary metabolite research.

PubMed

Breitling, Rainer; Ceniceros, Ana; Jankevics, Andris; Takano, Eriko

2013-11-11

Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and the engineered production of bioactive secondary metabolites.

Rotation relaxation splitting for optimizing parallel RF excitation pulses with T1 - and T2 -relaxations in MRI

NASA Astrophysics Data System (ADS)

Majewski, Kurt

2018-03-01

Exact solutions of the Bloch equations with T1 - and T2 -relaxation terms for piecewise constant magnetic fields are numerically challenging. We therefore investigate an approximation for the achieved magnetization in which rotations and relaxations are split into separate operations. We develop an estimate for its accuracy and explicit first and second order derivatives with respect to the complex excitation radio frequency voltages. In practice, the deviation between an exact solution of the Bloch equations and this rotation relaxation splitting approximation seems negligible. Its computation times are similar to exact solutions without relaxation terms. We apply the developed theory to numerically optimize radio frequency excitation waveforms with T1 - and T2 -relaxations in several examples.

Turning Towards or Turning Away: A Comparison of Mindfulness Meditation and Guided Imagery Relaxation in Patients with Acute Depression.

PubMed

Costa, Ana; Barnhofer, Thorsten

2016-07-01

Disengaging from maladaptive thinking is an important imperative in the treatment of depression. Mindfulness training is aimed at helping patients acquire relevant skills for this purpose. It remains unclear, however, whether this practice is helpful when patients are acutely depressed. In order to investigate effects of mindfulness on symptoms and self-regulatory capacities in this group, the current study compared a brief training in mindfulness (n = 19) to guided imagery relaxation (n = 18). Participants were introduced to the respective techniques in a single session, and practised daily over one week. Self-reported severity of symptoms, difficulties in emotion-regulation, attentional control, the ability to decentre, and mindfulness were assessed pre and postintervention, and at a one-week follow-up. Symptoms of depression significantly decreased and self-regulatory functioning significantly increased in both groups, with changes being maintained during follow-up. When controlling for change in depressive symptoms, results showed significantly higher improvements in emotion regulation at follow-up in the mindfulness group. The ability to decentre predicted changes in symptoms from pre to postintervention, while mindfulness skills predicted changes in symptoms during the maintenance phase. The findings suggest that both practices can help to instigate reductions in symptoms and enhance self-regulatory functioning in depression. However, in order to improve emotion regulation above levels explained by reductions in symptoms more intentional mental training seems necessary. Furthermore, while the ability to disengage from negative patterns of thinking seems crucial for initial reduction of symptoms, maintenance of gains might require broader skills in mindfulness.

F-centers mechanism of long-term relaxation in lead zirconate-titanate based piezoelectric ceramics. 2. After-field relaxation

NASA Astrophysics Data System (ADS)

Ishchuk, V. M.; Kuzenko, D. V.

2016-08-01

The paper presents results of experimental study of the dielectric constant relaxation during aging process in Pb(Zr,Ti)O3 based solid solutions (PZT) after action of external DC electric field. The said process is a long-term one and is described by the logarithmic function of time. Reversible and nonreversible relaxation process takes place depending on the field intensity. The relaxation rate depends on the field strength also, and the said dependence has nonlinear and nonmonotonic form, if external field leads to domain disordering. The oxygen vacancies-based model for description of the long-term relaxation processes is suggested. The model takes into account the oxygen vacancies on the sample's surface ends, their conversion into F+- and F0-centers under external effects and subsequent relaxation of these centers into the simple oxygen vacancies after the action termination. F-centers formation leads to the violation of the original sample's electroneutrality, and generate intrinsic DC electric field into the sample. Relaxation of F-centers is accompanied by the reduction of the electric field, induced by them, and relaxation of the dielectric constant, as consequent effect.

Secondary metabolites from marine microorganisms.

PubMed

Kelecom, Alphonse

2002-03-01

After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

Cardiovascular effects of linalyl acetate in acute nicotine exposure.

PubMed

Kim, Ju Ri; Kang, Purum; Lee, Hui Su; Kim, Ka Young; Seol, Geun Hee

2017-04-24

Smoking is a risk factor for cardiovascular diseases as well as pulmonary dysfunction. In particular, adolescent smoking has been reported to have a higher latent risk for cardiovascular disease. Despite the risk to and vulnerability of adolescents to smoking, the mechanisms underlying the effects of acute nicotine exposure on adolescents remain unknown. This study therefore evaluated the mechanism underlying the effects of linalyl acetate on cardiovascular changes in adolescent rats with acute nicotine exposure. Parameters analyzed included heart rate (HR), systolic blood pressure, lactate dehydrogenase (LDH) activity, vascular contractility, and nitric oxide levels. Compared with nicotine alone, those treated with nicotine plus 10 mg/kg (p = 0.036) and 100 mg/kg (p = 0.023) linalyl acetate showed significant reductions in HR. Moreover, the addition of 1 mg/kg (p = 0.011), 10 mg/kg (p = 0.010), and 100 mg/kg (p = 0.011) linalyl acetate to nicotine resulted in significantly lower LDH activity. Nicotine also showed a slight relaxation effect, followed by a sustained recontraction phase, whereas nicotine plus linalyl acetate or nifedipine showed a constant relaxation effect on contraction of mouse aorta (p < 0.001). Furthermore, nicotine-induced increases in nitrite levels were decreased by treatment with linalyl acetate (p < 0.001). Taken together, our findings suggest that linalyl acetate treatment resulted in recovery of cell damage and cardiovascular changes caused by acute nicotine-induced cardiovascular disruption. Our evaluation of the influence of acute nicotine provides potential insights into the effects of environmental tobacco smoke and suggests linalyl acetate as an available mitigating agent.

Evolving fuzzy rules for relaxed-criteria negotiation.

PubMed

Sim, Kwang Mong

2008-12-01

In the literature on automated negotiation, very few negotiation agents are designed with the flexibility to slightly relax their negotiation criteria to reach a consensus more rapidly and with more certainty. Furthermore, these relaxed-criteria negotiation agents were not equipped with the ability to enhance their performance by learning and evolving their relaxed-criteria negotiation rules. The impetus of this work is designing market-driven negotiation agents (MDAs) that not only have the flexibility of relaxing bargaining criteria using fuzzy rules, but can also evolve their structures by learning new relaxed-criteria fuzzy rules to improve their negotiation outcomes as they participate in negotiations in more e-markets. To this end, an evolutionary algorithm for adapting and evolving relaxed-criteria fuzzy rules was developed. Implementing the idea in a testbed, two kinds of experiments for evaluating and comparing EvEMDAs (MDAs with relaxed-criteria rules that are evolved using the evolutionary algorithm) and EMDAs (MDAs with relaxed-criteria rules that are manually constructed) were carried out through stochastic simulations. Empirical results show that: 1) EvEMDAs generally outperformed EMDAs in different types of e-markets and 2) the negotiation outcomes of EvEMDAs generally improved as they negotiated in more e-markets.

Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing.

PubMed

Jacobs, Peter L; Ridder, Lars; Ruijken, Marco; Rosing, Hilde; Jager, Nynke Gl; Beijnen, Jos H; Bas, Richard R; van Dongen, William D

2013-09-01

Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction, high-resolution accurate mass LC-MS and MS vendor independent data processing. Retrospective evaluation of predictions for 14 (14)C-ADME studies published in the period 2007-January 2012 indicates that on average 90% of the major metabolites in human plasma can be identified by searching for accurate masses of predicted metabolites. Furthermore, the workflow can identify unexpected metabolites in the same processing run, by differential analysis of samples of drug-dosed subjects and (placebo-dosed, pre-dose or otherwise blank) control samples. To demonstrate the utility of the workflow we applied it to identify tamoxifen metabolites in serum of a breast cancer patient treated with tamoxifen. Previously published metabolites were confirmed in this study and additional metabolites were identified, two of which are discussed to illustrate the advantages of the workflow.

The in vivo relaxivity of MRI contrast agents

NASA Astrophysics Data System (ADS)

Shuter, Borys

1999-11-01

Post-contrast clinical 1H Magnetic Resonance Images have to date been interpreted with little regard for possible variations in the in-vivo properties of injected magnetic pharmaceuticals (contrast agents), particularly in their relaxivity or ability to alter tissue relaxation rates, T2-1 and T 2-1, per unit concentration. The relaxivities of contrast agents have only rarely been measured in-vivo, measurements usually being performed on excised tissues and at magnetic field strengths lower than used in clinical practice. Some researchers have simply assumed that relaxivities determined in homogeneous tissue phantoms were applicable in-vivo. In this thesis, the relaxivities of two contrast agents, Gd-DTPA and Gd-EOB-DTPA, were measured in simple tissue phantoms and in the kidney and liver of intact, but sacrificed, Wistar rats using a clinical MR scanner with a magnetic field of 1.5 Tesla. T1 and T2 were determined from sets of images acquired using a standard clinical spin-echo pulse sequence. The contrast agent concentration in tissue was assessed by radioassay of 153Gd-DTPA or 153Gd-EOB-DTPA, mixed with the normal compound prior to injection. Relaxivity was taken as the slope of a linear regression fit of relaxation rate against Gd concentration. The relaxivities of Gd-EOB-DTPA were similarly determined in normal and biliary- obstructed guinea pigs. Relaxivities in tissue differed significantly from values obtained in simple phantoms. Kidney T1 relaxivity was reduced for both compounds in normal animals. Three days or more of biliary obstruction produced further reductions in kidney T1 relaxivity of Gd-EOB-DTPA, providing strong evidence that disease affects contrast agent relaxivity. Kidney T2 relaxivity was much greater than T1 relaxivity and was also depressed by biliary obstruction. Liver T1 and T 2 relaxivites were increased above phantom values, but were not affected by the biliary obstruction. Water compartmentalisation, macromolecular binding, proton

Metronidazole pharmacokinetics in patients with acute renal failure.

PubMed

Somogyi, A A; Kong, C B; Gurr, F W; Sabto, J; Spicer, W J; McLean, A J

1984-02-01

The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.

Role of inducible nitric oxide synthase in endothelium‐independent relaxation to raloxifene in rat aorta

PubMed Central

Au, Chak Leung; Tsang, Suk Ying; Lau, Chi Wai; Yao, Xiaoqiang; Cai, Zongwei

2017-01-01

Background and Purpose Raloxifene can induce both endothelium‐dependent and ‐independent relaxation in different arteries. However, the underlying mechanisms by which raloxifene triggers endothelium‐independent relaxation are still incompletely understood. The purpose of present study was to examine the roles of NOSs and Ca2+ channels in the relaxant response to raloxifene in the rat isolated, endothelium‐denuded aorta. Experimental Approach Changes in isometric tension, cGMP, nitrite, inducible NOS protein expression and distribution in response to raloxifene in endothelium‐denuded aortic rings were studied by organ baths, radioimmunoassay, Griess reaction, western blot and immunohistochemistry respectively. Key Results Raloxifene reduced the contraction to CaCl2 in a Ca2+‐free, high K+‐containing solution in intact aortic rings. Raloxifene also acutely relaxed the aorta primarily through an endothelium‐independent mechanism involving NO, mostly from inducible NOS (iNOS) in vascular smooth muscle layers. This effect of raloxifene involved the generation of cGMP and nitrite. Also, it was genomic in nature, as it was inhibited by a classical oestrogen receptor antagonist and inhibitors of RNA and protein synthesis. Raloxifene‐induced stimulation of iNOS gene expression was partly mediated through activation of the NF‐κB pathway. Raloxifene was more potent than 17β‐estradiol or tamoxifen at relaxing endothelium‐denuded aortic rings by stimulation of iNOS. Conclusions and Implications Raloxifene‐mediated vasorelaxation in rat aorta is independent of a functional endothelium and is mediated by oestrogen receptors and NF‐κB. This effect is mainly mediated through an enhanced production of NO, cGMP and nitrite, via the induction of iNOS and inhibition of calcium influx through Ca2+ channels in rat aortic smooth muscle. PMID:28138957

Thermodynamic scaling of α-relaxation time and viscosity stems from the Johari-Goldstein β-relaxation or the primitive relaxation of the coupling model.

PubMed

Ngai, K L; Habasaki, J; Prevosto, D; Capaccioli, S; Paluch, Marian

2012-07-21

By now it is well established that the structural α-relaxation time, τ(α), of non-associated small molecular and polymeric glass-formers obey thermodynamic scaling. In other words, τ(α) is a function Φ of the product variable, ρ(γ)/T, where ρ is the density and T the temperature. The constant γ as well as the function, τ(α) = Φ(ρ(γ)/T), is material dependent. Actually this dependence of τ(α) on ρ(γ)/T originates from the dependence on the same product variable of the Johari-Goldstein β-relaxation time, τ(β), or the primitive relaxation time, τ(0), of the coupling model. To support this assertion, we give evidences from various sources itemized as follows. (1) The invariance of the relation between τ(α) and τ(β) or τ(0) to widely different combinations of pressure and temperature. (2) Experimental dielectric and viscosity data of glass-forming van der Waals liquids and polymer. (3) Molecular dynamics simulations of binary Lennard-Jones (LJ) models, the Lewis-Wahnström model of ortho-terphenyl, 1,4 polybutadiene, a room temperature ionic liquid, 1-ethyl-3-methylimidazolium nitrate, and a molten salt 2Ca(NO(3))(2)·3KNO(3) (CKN). (4) Both diffusivity and structural relaxation time, as well as the breakdown of Stokes-Einstein relation in CKN obey thermodynamic scaling by ρ(γ)/T with the same γ. (5) In polymers, the chain normal mode relaxation time, τ(N), is another function of ρ(γ)/T with the same γ as segmental relaxation time τ(α). (6) While the data of τ(α) from simulations for the full LJ binary mixture obey very well the thermodynamic scaling, it is strongly violated when the LJ interaction potential is truncated beyond typical inter-particle distance, although in both cases the repulsive pair potentials coincide for some distances.

'Relaxers' damage hair: evidence from amino acid analysis.

PubMed

Khumalo, Nonhlanhla P; Stone, Janet; Gumedze, Freedom; McGrath, Emily; Ngwanya, Mzudumile R; de Berker, David

2010-03-01

'Relaxers' are used by more than two thirds of African females to straighten hair, with easy grooming and increased length often cited as reasons. A recent study reported relaxed hair lengths much shorter than expected, suggesting increased fragility; the potential for scalp inflammation and scarring alopecia remains unclear. To investigate the biochemical effects of 'relaxers' on hair. With informed consent, included participants represented 3 groups: natural hair, asymptomatic relaxed hair, and symptomatic (brittle) relaxed hair. Biochemical analysis was performed by using a Biochrom 30 amino acid analyzer. Differences in amino acid levels were assessed using either Wilcoxon rank sum test or matched-pairs signed-rank test. There was a decrease in cystine, citrulline, and arginine; however, an increase in glutamine was found in all relaxed compared to natural hair. Cystine levels (milligram per gram amino acid nitrogen) were similar in natural proximal and distal hair: 14 mg/g (range, 4-15 mg/g) versus 14 mg/g (range, 12-15 mg/g); P = .139. In asymptomatic relaxed hair, cystine levels were higher in less frequently relaxed samples proximal to scalp: 7.5 mg/g (5.6-12) versus 3.3 mg/g (1.3-9.2); P = .005. Cystine levels in distal asymptomatic relaxed and symptomatic relaxed hair were similar to each other and to those in the genetic hair fragility disease trichothiodystrophy. It was not possible to analyze lye and no-lye 'relaxers' separately. 'Relaxers' are associated with reduced cystine consistent with fragile damaged hair. A decrease in citrulline and glutamine has been associated with inflammation; prospective studies are needed to investigate whether or how 'relaxers' induce inflammation. Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue.

PubMed

Rooney, O M; Troke, J; Nicholson, J K; Griffin, J L

2003-11-01

High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T(1) and T(2) relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral-editing using T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T(2) spin echo was included in a standard stimulated gradient spin-echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co-resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO. Copyright 2003 Wiley-Liss, Inc.

Can Black Hole Relax Unitarily?

NASA Astrophysics Data System (ADS)

Solodukhin, S. N.

2005-03-01

We review the way the BTZ black hole relaxes back to thermal equilibrium after a small perturbation and how it is seen in the boundary (finite volume) CFT. The unitarity requires the relaxation to be quasi-periodic. It is preserved in the CFT but is not obvious in the case of the semiclassical black hole the relaxation of which is driven by complex quasi-normal modes. We discuss two ways of modifying the semiclassical black hole geometry to maintain unitarity: the (fractal) brick wall and the worm-hole modification. In the latter case the entropy comes out correctly as well.

Rapid wall relaxation in elongating tissues.

PubMed

Matyssek, R; Maruyama, S; Boyer, J S

1988-04-01

Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision.

Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

PubMed

Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

2018-06-01

Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

Spatially resolved nuclear spin relaxation, electron spin relaxation and light absorption in swift heavy ion irradiated LiF crystals.

PubMed

Stork, H; Dinse, K-P; Ditter, M; Fujara, F; Masierak, W; Neumann, R; Schuster, B; Schwartz, K; Trautmann, C

2010-05-12

Spatially resolved (19)F and (7)Li spin-lattice relaxation rates are measured for LiF single crystals after irradiation with two kinds of swift heavy ions ((12)C of 133 MeV and (208)Pb of 1.78 GeV incident energy). Like in earlier studies on (130)Xe and (238)U irradiated LiF crystals, we found a strong enhancement of the nuclear spin-lattice relaxation rate within the ion penetration depth and a slight--but still significant--enhancement beyond. By evaluating the nuclear relaxation rate enhancement within the ion range after irradiation with different projectiles, a universal relationship between the spin-lattice relaxation rate and the dose is deduced. The results of accompanying X-band electron paramagnetic resonance relaxation measurements and optical absorption spectroscopy are included in a physical interpretation of this relationship. Also the reason for the enhanced relaxation rate beyond the ion range is further discussed.

Reduced myo-inositol and total choline measured with cerebral MRS in acute thyrotoxic Graves' disease.

PubMed

Elberling, T V; Danielsen, E R; Rasmussen, A K; Feldt-Rasmussen, U; Waldemar, G; Thomsen, C

2003-01-14

Neuropsychiatric symptoms in the acute thyrotoxic phase of Graves' disease suggest involvement of brain processes. Short-echo-time proton MRS was used to measure the cerebral metabolite profile in newly diagnosed and untreated Graves' disease. Sixteen patients with Graves' disease and 18 age- and sex-matched healthy volunteers were studied. The patients had significantly reduced total choline and myo-inositol in the acute phase of Graves' thyrotoxicosis compared with the healthy volunteers.

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

PubMed Central

Miller, Desinia B.; Ghio, Andrew J.; Karoly, Edward D.; Bell, Lauren N.; Snow, Samantha J.; Madden, Michael C.; Soukup, Joleen; Cascio, Wayne E.; Gilmour, M. Ian

2016-01-01

Rationale: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism. Objectives: To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers. Methods: Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach. Measurements and Main Results: Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation–derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans. Conclusions: As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01492517

Microsomal metabolism of trenbolone acetate metabolites ...

EPA Pesticide Factsheets

Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

Acute Heart Failure Triggered by Coronary Spasm With Transient Left Ventricular Dysfunction.

PubMed

Adachi, Yusuke; Sakakura, Kenichi; Ibe, Tatsuro; Yoshida, Nanae; Wada, Hiroshi; Fujita, Hideo; Momomura, Shin-Ichi

2017-04-06

Coronary spasm is abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia. Coronary spasm induces not only depressed myocardial contractility, but also incomplete myocardial relaxation, which leads to elevated ventricular filling pressure. We herein report the case of a 55-year-old woman who had repeated acute heart failure caused by coronary spasm. Acetylcholine provocation test with simultaneous right heart catheterization was useful for the diagnosis of elevated ventricular filling pressure as well as coronary artery spasm. We should add coronary spasm to a differential diagnosis for repeated acute heart failure.

Quasiparticle relaxation in superconducting nanostructures

NASA Astrophysics Data System (ADS)

Savich, Yahor; Glazman, Leonid; Kamenev, Alex

2017-09-01

We examine energy relaxation of nonequilibrium quasiparticles in "dirty" superconductors with the electron mean free path much shorter than the superconducting coherence length. Relaxation of low-energy nonequilibrium quasiparticles is dominated by phonon emission. We derive the corresponding collision integral and find the quasiparticle relaxation rate. The latter is sensitive to the breaking of time reversal symmetry (TRS) by a magnetic field (or magnetic impurities). As a concrete application of the developed theory, we address quasiparticle trapping by a vortex and a current-biased constriction. We show that trapping of hot quasiparticles may predominantly occur at distances from the vortex core, or the constriction, significantly exceeding the superconducting coherence length.

Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

PubMed

Mena, Pedro; Ludwig, Iziar A; Tomatis, Virginia B; Acharjee, Animesh; Calani, Luca; Rosi, Alice; Brighenti, Furio; Ray, Sumantra; Griffin, Julian L; Bluck, Les J; Del Rio, Daniele

2018-04-03

There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

Hydroquinone, a benzene metabolite, and leukemia: a case report and review of the literature.

PubMed

Regev, Lee; Wu, Michael; Zlotolow, Ronald; Brautbar, Nachman

2012-02-01

Hydroquinone is a phenolic metabolite of benzene, a known human carcinogen. Hydroquinone is widely used in the industry. We report a case of a 43-year-old male diagnosed with antecedent myelodysplastic syndrome and acute myeloid leukemia following 16 years of occupational exposure to hydroquinone in radiographic developer solution. Cytogenetic studies revealed aberrations in chromosome 5 and chromosome 7. We review the literature on hydroquinone as a potential cause of hematolymphatic cancers and discuss the role of hydroquinone as a genotoxic and leukemogenic agent.

Characterization of macromolecular baseline of human brain using metabolite cycled semi-LASER at 9.4T.

PubMed

Giapitzakis, Ioannis-Angelos; Avdievich, Nikolai; Henning, Anke

2018-08-01

Macromolecular resonances (MM) arise mainly from cytosolic proteins and overlap with metabolites, influencing metabolite quantification. Macromolecules can serve as valuable biomarkers for diseases and pathologies. The objectives of this study were to characterize MM at 9.4T in the human brain (occipital and left parietal lobe) and to describe the RF coil setup used for MM acquisition in the two regions. An adiabatic inversion pulse was optimised for metabolite nulling at 9.4T using double inversion recovery and was combined for the first time with metabolite cycled (MC) semi-LASER and appropriate coil configuration. MM spectra (seven volunteers) from two brain locations were averaged and smoothed creating MM templates, which were then parametrized using simulated Voigt-shaped lines within LCModel. Quantification was performed on individual data sets, including corrections for different tissue composition and the T 1 and T 2 relaxation of water. Our coil configuration method resulted in efficient B1+ (>30 T/√kW) for both brain regions. The 15 MM components were detected and quantified in MM baselines of the two brain areas. No significant differences in concentration levels of MM between different regions were found. Two new MM peaks were reported (M7 & M8). Double inversion, which was combined with MC semi-LASER, enabled the acquisition of high spectral resolution MM spectra for both brain regions at 9.4T. The 15 MM components were detected and quantified. Two new MM peaks were reported for the first time (M7 & M8) and preliminarily assigned to β-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

[Autocontrol of muscle relaxation with vecuronium].

PubMed

Sibilla, C; Zatelli, R; Marchi, M; Zago, M

1990-01-01

The optimal conditions for maintaining desired levels of muscle relaxation with vecuronium are obtained by means of the continuous infusion (I.V.) technique. A frequent correction of the infusion flow is required, since it is impossible to predict the exact amount for the muscle relaxant in single case. In order to overcome such limits the authors propose a very feasible infusion system for the self-control of muscle relaxation; furthermore they positively consider its possible daily clinical application.

Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations.

PubMed

Moyad, Mark A; Combs, Maile A; Vrablic, Angelica S; Velasquez, Janet; Turner, Benilda; Bernal, Samuel

2008-10-01

The objective of this study was to test the effects of acute doses of vitamin C alone, calcium ascorbate with vitamin C metabolites, and placebo, on total plasma and leukocyte vitamin C concentrations over 24 hours. A double-blind, placebo-controlled, four-way crossover study was performed consisting of four separate phases lasting 24 hours each and utilizing one of four oral 1000-mg preparations within each phase (one of vitamin C alone, two separate vitamin C formulations of calcium ascorbate with vitamin C metabolites, and placebo). There was a 7-day washout between phases, and blood draws at seven time points within each phase of the study for a total of 28 serologic measurements per subject and 420 total measurements for the entire clinical trial. Vitamin C concentration in plasma and leukocytes were measured by high-performance liquid chromatography at baseline and at six sequential time periods over 24 hours. Fifteen healthy males were enrolled, aged 18-39 years; nine were had never smoked and six were chronic smokers. No significant difference in plasma vitamin C levels was observed when comparing the different preparations. However, at 24 hours, calcium ascorbate with metabolites resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) compared with vitamin C alone. These results were similar for both metabolite formulations, and independent of smoking status. Regardless of smoking status, vitamin C metabolites may enhance leukocyte utilization of vitamin C itself, despite no consistent difference in plasma levels among the different preparations. A larger clinical investigation is warranted to confirm these preliminary findings, and to determine the clinical relevance of this impact on overall immune function.

LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards.

PubMed

Zhang, Donglu; Raghavan, Nirmala; Chando, Theodore; Gambardella, Janice; Fu, Yunlin; Zhang, Duxi; Unger, Steve E; Humphreys, W Griffith

2007-12-01

An LC-MS/MS-based approach that employs authentic radioactive metabolites as reference standards was developed to estimate metabolite exposures in early drug development studies. This method is useful to estimate metabolite levels in studies done with non-radiolabeled compounds where metabolite standards are not available to allow standard LC-MS/MS assay development. A metabolite mixture obtained from an in vivo source treated with a radiolabeled compound was partially purified, quantified, and spiked into human plasma to provide metabolite standard curves. Metabolites were analyzed by LC-MS/MS using the specific mass transitions and an internal standard. The metabolite concentrations determined by this approach were found to be comparable to those determined by valid LC-MS/MS assays. This approach does not requires synthesis of authentic metabolites or the knowledge of exact structures of metabolites, and therefore should provide a useful method to obtain early estimates of circulating metabolites in early clinical or toxicological studies.

New Pioglitazone Metabolites and Absence of Opened-Ring Metabolites in New N-Substituted Thiazolidinedione.

PubMed

Campos, Michel Leandro; Cerqueira, Letícia Bonancio; Silva, Bruna Cristina Ulian; Franchin, Taísa Busaranho; Galdino-Pitta, Marina Rocha; Pitta, Ivan Rocha; Peccinini, Rosângela Gonçalves; Pontarolo, Roberto

2018-06-01

Thiazolidinediones (TZDs) are drugs used to treat type 2 diabetes mellitus; however, several safety concerns remain regarding the available drugs in this class. Therefore, the search for new TZD candidates is ongoing; metabolism studies play a crucial step in the development of new candidates. Pioglitazone, one of the most commonly used TZDs, and GQ-11, a new N -substituted TZD, were investigated in terms of their metabolic activity in rat and human liver microsomes to assess their metabolic stability and investigate their metabolites. Methods for preparation of samples were based on liquid-liquid extraction and protein precipitation. Quantitation was performed using liquid chromatography (LC)-tandem mass spectrometry, and the metabolite investigation was performed using ultraperformance LC coupled to a hybrid quadrupole-time of flight mass spectrometer. The predicted intrinsic clearance of GQ-11 was 70.3 and 46.1 ml/kg per minute for rats and humans, respectively. The predicted intrinsic clearance of pioglitazone was 24.1 and 15.9 ml/kg per minute for rats and humans, respectively. The pioglitazone metabolite investigation revealed two unpublished metabolites (M-D and M-A). M-A is a hydration product and may be related to the mechanism of ring opening and the toxicity of pioglitazone. The metabolites of GQ-11 are products of oxidation; no ring-opening metabolite was observed for GQ-11. In conclusion, under the same experimental conditions, a ring-opening metabolite was observed only for pioglitazone. The resistance of GQ-11 to the ring opening is probably related to N -substitution in the TZD ring. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Magnetic Resonance Fingerprinting with short relaxation intervals.

PubMed

Amthor, Thomas; Doneva, Mariya; Koken, Peter; Sommer, Karsten; Meineke, Jakob; Börnert, Peter

2017-09-01

The aim of this study was to investigate a technique for improving the performance of Magnetic Resonance Fingerprinting (MRF) in repetitive sampling schemes, in particular for 3D MRF acquisition, by shortening relaxation intervals between MRF pulse train repetitions. A calculation method for MRF dictionaries adapted to short relaxation intervals and non-relaxed initial spin states is presented, based on the concept of stationary fingerprints. The method is applicable to many different k-space sampling schemes in 2D and 3D. For accuracy analysis, T 1 and T 2 values of a phantom are determined by single-slice Cartesian MRF for different relaxation intervals and are compared with quantitative reference measurements. The relevance of slice profile effects is also investigated in this case. To further illustrate the capabilities of the method, an application to in-vivo spiral 3D MRF measurements is demonstrated. The proposed computation method enables accurate parameter estimation even for the shortest relaxation intervals, as investigated for different sampling patterns in 2D and 3D. In 2D Cartesian measurements, we achieved a scan acceleration of more than a factor of two, while maintaining acceptable accuracy: The largest T 1 values of a sample set deviated from their reference values by 0.3% (longest relaxation interval) and 2.4% (shortest relaxation interval). The largest T 2 values showed systematic deviations of up to 10% for all relaxation intervals, which is discussed. The influence of slice profile effects for multislice acquisition is shown to become increasingly relevant for short relaxation intervals. In 3D spiral measurements, a scan time reduction of 36% was achieved, maintaining the quality of in-vivo T1 and T2 maps. Reducing the relaxation interval between MRF sequence repetitions using stationary fingerprint dictionaries is a feasible method to improve the scan efficiency of MRF sequences. The method enables fast implementations of 3D spatially

Active Components of Ginger Potentiate β-Agonist–Induced Relaxation of Airway Smooth Muscle by Modulating Cytoskeletal Regulatory Proteins

PubMed Central

Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W.

2014-01-01

β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist–induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C–potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist–induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms

MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS

EPA Science Inventory

In order to characterize the potential developmental effects of atrazine (ATR) metabolites at low doses, an environmentally-based mixture (EBM) of ATR and its metabolites hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine was formulated based on surv...

Relaxation and Distraction in Experimental Desensitization.

ERIC Educational Resources Information Center

Weir, R. O.; Marshall, W. L.

1980-01-01

Compared experimental desensitization with a procedure that replaced relaxation with a distraction task and with an approach that combined both relaxation and distraction. Desensitization generally was more effective than the other two procedures. (Author)

Distributed Relaxation for Conservative Discretizations

NASA Technical Reports Server (NTRS)

Diskin, Boris; Thomas, James L.

2001-01-01

A multigrid method is defined as having textbook multigrid efficiency (TME) if the solutions to the governing system of equations are attained in a computational work that is a small (less than 10) multiple of the operation count in one target-grid residual evaluation. The way to achieve this efficiency is the distributed relaxation approach. TME solvers employing distributed relaxation have already been demonstrated for nonconservative formulations of high-Reynolds-number viscous incompressible and subsonic compressible flow regimes. The purpose of this paper is to provide foundations for applications of distributed relaxation to conservative discretizations. A direct correspondence between the primitive variable interpolations for calculating fluxes in conservative finite-volume discretizations and stencils of the discretized derivatives in the nonconservative formulation has been established. Based on this correspondence, one can arrive at a conservative discretization which is very efficiently solved with a nonconservative relaxation scheme and this is demonstrated for conservative discretization of the quasi one-dimensional Euler equations. Formulations for both staggered and collocated grid arrangements are considered and extensions of the general procedure to multiple dimensions are discussed.

Ultra-Slow Dielectric Relaxation Process in Polyols

NASA Astrophysics Data System (ADS)

Yomogida, Yoshiki; Minoguchi, Ayumi; Nozaki, Ryusuke

2004-04-01

Dielectric relaxation processes with relaxation times larger than that for the structural α process are reported for glycerol, xylitol, sorbitol and their mixtures for the first time. Appearance of this ultra-slow process depends on cooling rate. More rapid cooling gives larger dielectric relaxation strength. However, relaxation time is not affected by cooling rate and shows non-Arrhenius temperature dependence with correlation to the α process. It can be considered that non-equilibrium dynamic structure causes the ultra-slow process. Scale of such structure would be much larger than that of the region for the cooperative molecular orientations for the α process.

Burkholderia pseudomallei Colony Morphotypes Show a Synchronized Metabolic Pattern after Acute Infection

PubMed Central

Steinmetz, Ivo; Lalk, Michael

2016-01-01

Background Burkholderia pseudomallei is a water and soil bacterium and the causative agent of melioidosis. A characteristic feature of this bacterium is the formation of different colony morphologies which can be isolated from environmental samples as well as from clinical samples, but can also be induced in vitro. Previous studies indicate that morphotypes can differ in a number of characteristics such as resistance to oxidative stress, cellular adhesion and intracellular replication. Yet the metabolic features of B. pseudomallei and its different morphotypes have not been examined in detail so far. Therefore, this study aimed to characterize the exometabolome of B. pseudomallei morphotypes and the impact of acute infection on their metabolic characteristics. Methods and Principal Findings We applied nuclear magnetic resonance spectroscopy (1H-NMR) in a metabolic footprint approach to compare nutrition uptake and metabolite secretion of starvation induced morphotypes of the B. pseudomallei strains K96243 and E8. We observed gluconate production and uptake in all morphotype cultures. Our study also revealed that among all morphotypes amino acids could be classified with regard to their fast and slow consumption. In addition to these shared metabolic features, the morphotypes varied highly in amino acid uptake profiles, secretion of branched chain amino acid metabolites and carbon utilization. After intracellular passage in vitro or murine acute infection in vivo, we observed a switch of the various morphotypes towards a single morphotype and a synchronization of nutrient uptake and metabolite secretion. Conclusion To our knowledge, this study provides first insights into the basic metabolism of B. pseudomallei and its colony morphotypes. Furthermore, our data suggest, that acute infection leads to the synchronization of B. pseudomallei colony morphology and metabolism through yet unknown host signals and bacterial mechanisms. PMID:26943908

Convex relaxations for gas expansion planning

DOE PAGES

Borraz-Sanchez, Conrado; Bent, Russell Whitford; Backhaus, Scott N.; ...

2016-01-01

Expansion of natural gas networks is a critical process involving substantial capital expenditures with complex decision-support requirements. Here, given the non-convex nature of gas transmission constraints, global optimality and infeasibility guarantees can only be offered by global optimisation approaches. Unfortunately, state-of-the-art global optimisation solvers are unable to scale up to real-world size instances. In this study, we present a convex mixed-integer second-order cone relaxation for the gas expansion planning problem under steady-state conditions. The underlying model offers tight lower bounds with high computational efficiency. In addition, the optimal solution of the relaxation can often be used to derive high-quality solutionsmore » to the original problem, leading to provably tight optimality gaps and, in some cases, global optimal solutions. The convex relaxation is based on a few key ideas, including the introduction of flux direction variables, exact McCormick relaxations, on/off constraints, and integer cuts. Numerical experiments are conducted on the traditional Belgian gas network, as well as other real larger networks. The results demonstrate both the accuracy and computational speed of the relaxation and its ability to produce high-quality solution« less

Accuracy investigation of phthalate metabolite standards.

PubMed

Langlois, Éric; Leblanc, Alain; Simard, Yves; Thellen, Claude

2012-05-01

Phthalates are ubiquitous compounds whose metabolites are usually determined in urine for biomonitoring studies. Following suspect and unexplained results from our laboratory in an external quality-assessment scheme, we investigated the accuracy of all phthalate metabolite standards in our possession by comparing them with those of several suppliers. Our findings suggest that commercial phthalate metabolite certified solutions are not always accurate and that lot-to-lot discrepancies significantly affect the accuracy of the results obtained with several of these standards. These observations indicate that the reliability of the results obtained from different lots of standards is not equal, which reduces the possibility of intra-laboratory and inter-laboratory comparisons of results. However, agreements of accuracy have been observed for a majority of neat standards obtained from different suppliers, which indicates that a solution to this issue is available. Data accuracy of phthalate metabolites should be of concern for laboratories performing phthalate metabolite analysis because of the standards used. The results of our investigation are presented from the perspective that laboratories performing phthalate metabolite analysis can obtain accurate and comparable results in the future. Our findings will contribute to improving the quality of future phthalate metabolite analyses and will affect the interpretation of past results.

Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in Shanghai.

PubMed

Ding, Guodong; Shi, Rong; Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Wang, Guoquan; Feng, Chao; Tian, Ying

2012-12-18

Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.

Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry.

PubMed

Feliciano, Rodrigo P; Istas, Geoffrey; Heiss, Christian; Rodriguez-Mateos, Ana

2016-08-25

Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%-48% in plasma and 47%-54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption.

Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis.

PubMed

Chan, Wui Ling; Wood, David M; Hudson, Simon; Dargan, Paul I

2013-09-01

There is evidence from around Europe of the availability and use of 6-(2-aminopropyl)benzofuran (6-APB) as a recreational drug. However, there is currently limited information on the acute toxicity of this compound. We describe here a case of acute toxicity associated with recreational use of legal high (6-APB) and cannabis, in which the comprehensive toxicological analysis confirmed the presence of a significant amount of 6-APB together with metabolites of both tetrahydrocannabinol and the synthetic cannabinoid receptor agonist (JWH-122). A 21-year-old gentleman with no previous medical and psychiatric history was brought to the emergency department (ED) after he had developed agitation and paranoid behaviour following the use of 6-APB purchased over the Internet. There was no obvious medical cause for his acute psychosis. He required diazepam to control his agitation and was subsequently transferred to a psychiatric hospital for ongoing management of his psychosis. Toxicological screening of a urine sample collected after presentation to the ED detected 6-APB, with an estimated urinary concentration of 2,000 ng/ml; other drugs were also detected, but at lower concentrations including metabolites of the synthetic cannabinoid receptor agonist JWH-122 and tetrahydrocannabinol. This is the first case of analytically confirmed acute toxicity associated with the detection of 6-APB which will provide some information on acute toxicity of this drug to help clinicians with the management of such patients and legislative authorities in their consideration for the need of its control.

Lavender fragrance cleansing gel effects on relaxation.

PubMed

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Cisneros, Wendy; Feijo, Larissa; Vera, Yanexy; Gil, Karla; Grina, Diana; Claire He, Qing

2005-02-01

Alertness, mood, and math computations were assessed in 11 healthy adults who sniffed a cosmetic cleansing gel with lavender floral blend aroma, developed to be relaxing using Mood Mapping. EEG patterns and heart rate were also recorded before, during, and after the aroma session. The lavender fragrance blend had a significant transient effect of improving mood, making people feel more relaxed, and performing the math computation faster. The self-report and physiological data are consistent with relaxation profiles during other sensory stimuli such as massage and music, as reported in the literature. The data suggest that a specific cosmetic fragrance can have a significant role in enhancing relaxation.

Enhanced metabolite generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chidambaram, Devicharan

The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

Acute bilateral ureteral obstruction secondary to guaifenesin toxicity.

PubMed

Cockerill, Patrick A; de Cógáin, Mitra R; Krambeck, Amy E

2013-10-01

Several medications or their metabolites have been associated with urolithiasis, although overall they remain an infrequent cause of urolithiasis. Guaifenesin stones were originally reported as complexed with ephedrine, and subsequent reports have demonstrated pure guaifenesin stones, occurring after long term abuse. We report a case of a 23-year-old male who ingested a large, one time dose of guaifenesin, resulting in acute bilateral ureteral obstruction, which, to our knowledge, is the first such reported case in the literature.

Acute renal failure after ingestion of guaifenesin and dextromethorphan.

PubMed

Small, Evan; Sandefur, Benjamin J

2014-07-01

Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of proflavine metabolites in rainbow trout.

PubMed

Yu, Z; Hayton, W L; Chan, K K

1997-04-01

Proflavine (3,6-diaminoacridine) has potential for use as an antiinfective in fish, and its metabolism by rainbow trout was therefore studied. Fourteen hours after intraarterial bolus administration of 10 mg/kg of proflavine, three metabolites were found in liver and bile, and one metabolite was found in plasma using reversed-phase HPLC with UV detection at 262 nm. Treatment with hydrochloric acid converted the three metabolites to proflavine, which suggested that the metabolites were proflavine conjugates. Treatment with beta-glucuronidase and saccharic acid 1,4-lactone, a specific beta-glucuronidase inhibitor, revealed that two metabolites were proflavine glucuronides. For determination of UV-VIS absorption and mass spectra, HPLC-purified metabolites were isolated from liver. Data from these experiments suggested that the proflavine metabolites were 3-N-glucuronosyl proflavine (PG), 3-N-glucuronosyl,6-N-acetyl proflavine (APG), and 3-N-acetylproflavine (AP). The identities of the metabolites were verified by chemical synthesis. When synthetic PG and AP were compared with the two metabolites isolated from trout, they had the same molecular weight as determined by matrix-assisted, laser desorption ionization, time-of-flight MS. In addition, they coeluted on HPLC under different mobile phase conditions. Finally, the in vitro incubation with liver subcellular preparations confirmed this characterization and provided the evidence that APG can be formed by glucuronidation of AP or acetylation of PG.

Magnetic relaxation pathways in lanthanide single-molecule magnets.

PubMed

Blagg, Robin J; Ungur, Liviu; Tuna, Floriana; Speak, James; Comar, Priyanka; Collison, David; Wernsdorfer, Wolfgang; McInnes, Eric J L; Chibotaru, Liviu F; Winpenny, Richard E P

2013-08-01

Single-molecule magnets are compounds that exhibit magnetic bistability caused by an energy barrier for the reversal of magnetization (relaxation). Lanthanide compounds are proving promising as single-molecule magnets: recent studies show that terbium phthalocyanine complexes possess large energy barriers, and dysprosium and terbium complexes bridged by an N2(3-) radical ligand exhibit magnetic hysteresis up to 13 K. Magnetic relaxation is typically controlled by single-ion factors rather than magnetic exchange (whether one or more 4f ions are present) and proceeds through thermal relaxation of the lowest excited states. Here we report polylanthanide alkoxide cage complexes, and their doped diamagnetic yttrium analogues, in which competing relaxation pathways are observed and relaxation through the first excited state can be quenched. This leads to energy barriers for relaxation of magnetization that exceed 800 K. We investigated the factors at the lanthanide sites that govern this behaviour.

Analysis of variability of concentrations of valproic acid (VPA) and its selected metabolites in the blood serum of patients treated with VPA and patients hospitalized because of VPA poisoning.

PubMed

Wilimowska, J; Kłys, M; Jawień, W

2014-01-01

To compare the metabolic profile of valproic acid (VPA) in the studied groups of cases through an analysis of variability of concentrations of VPA with its selected metabolites (2-ene-VPA, 4-ene-VPA, 3-keto-VPA). Blood serum samples collected from 27 patients treated with VPA drugs in the Psychiatry Unit and in the Neurology and Cerebral Strokes Unit at the Ludwik Rydygier Provincial Specialist Hospital in Krakow, and blood serum samples collected from 26 patients hospitalized because of suspected acute VPA poisoning at the Toxicology Department, Chair of Toxicology and Environmental Diseases, Jagiellonian University Medical College in Krakow. The analysis of concentrations of VPA and its selected metabolites has shown that the metabolic profile of VPA determined in cases of acute poisoning is different from cases of VPA therapy. One of VPA's metabolic pathways - the process of desaturation - is unchanged in acute poisoning and prevails over the process of β-oxidation. The ingestion of toxic VPA doses results in an increased formation of 4-ene-VPA, proportional to an increase in VPA concentration. Acute VPA poisoning involves the saturation of VPA's metabolic transformations at the stage of β-oxidation. The process of oxidation of 2-ene-VPA to 3-keto-VPA is slowed down after the ingestion of toxic doses.

Relaxation versus adiabatic quantum steady-state preparation

NASA Astrophysics Data System (ADS)

Venuti, Lorenzo Campos; Albash, Tameem; Marvian, Milad; Lidar, Daniel; Zanardi, Paolo

2017-04-01

Adiabatic preparation of the ground states of many-body Hamiltonians in the closed-system limit is at the heart of adiabatic quantum computation, but in reality systems are always open. This motivates a natural comparison between, on the one hand, adiabatic preparation of steady states of Lindbladian generators and, on the other hand, relaxation towards the same steady states subject to the final Lindbladian of the adiabatic process. In this work we thus adopt the perspective that the goal is the most efficient possible preparation of such steady states, rather than ground states. Using known rigorous bounds for the open-system adiabatic theorem and for mixing times, we are then led to a disturbing conclusion that at first appears to doom efforts to build physical quantum annealers: relaxation seems to always converge faster than adiabatic preparation. However, by carefully estimating the adiabatic preparation time for Lindbladians describing thermalization in the low-temperature limit, we show that there is, after all, room for an adiabatic speedup over relaxation. To test the analytically derived bounds for the adiabatic preparation time and the relaxation time, we numerically study three models: a dissipative quasifree fermionic chain, a single qubit coupled to a thermal bath, and the "spike" problem of n qubits coupled to a thermal bath. Via these models we find that the answer to the "which wins" question depends for each model on the temperature and the system-bath coupling strength. In the case of the "spike" problem we find that relaxation during the adiabatic evolution plays an important role in ensuring a speedup over the final-time relaxation procedure. Thus, relaxation-assisted adiabatic preparation can be more efficient than both pure adiabatic evolution and pure relaxation.

Rapid Wall Relaxation in Elongating Tissues 1

PubMed Central

Matyssek, Rainer; Maruyama, Sachio; Boyer, John S.

1988-01-01

Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max [L.] Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, we investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. We found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached to the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. Previous reports of wall relaxation in pea included slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold should be constant during so short a time, thus reflecting the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species. The presence of slowly growing or mature tissue delays wall relaxation and should be avoided during such measurements. However, this delay can be used to advantage when turgor of intact growing tissues is being measured using excised tissues because turgor does not change for a considerable time after excision. PMID:16666048

The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: correlation with beta-glucuronidase activity.

PubMed

Perez, Almudena; Gonzalez-Manzano, Susana; Jimenez, Rosario; Perez-Abud, Rocío; Haro, Jose M; Osuna, Antonio; Santos-Buelga, Celestino; Duarte, Juan; Perez-Vizcaino, Francisco

2014-11-01

Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in hypertensive humans and animal models. We hypothesized that oral quercetin might induce vasodilator effects in humans and that they might be related to the deconjugation of quercetin-3-O-glucuronide (Q3GA). double blind, randomized, placebo-controlled trial. Fifteen healthy volunteers (26±5 years, 6 female) were given a capsule containing placebo, 200 or 400mg of quercetin in random order in three consecutive weeks. At 2h a dose-dependent increase in Q3GA was observed in plasma (∼0.4 and 1μM for 200 and 400mg, respectively) with minor levels of quercetin and isorhamnetin. No changes were observed in blood pressure. At 5h quercetin induced and increase in brachial arterial diameter that correlated with the product of the levels of Q3GA by the plasma glucuronidase activity. There was an increase in urinary levels of glutathione but there was no increase in nitrites plus nitrates. Quercetin and isorhamnetin also relaxed human umbilical arteries in vitro while Q3GA was without effect. In conclusions, quercetin exerts acute vasodilator effects in vivo in normotensive, normocholesterolemic human subjects. These results are consistent with the effects being due to the deconjugation of the metabolite Q3GA. Copyright © 2014 Elsevier Ltd. All rights reserved.

SERUM metabolomics of acute lymphoblastic leukaemia and acute myeloid leukaemia for probing biomarker molecules.

PubMed

Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Naz, Arshi

2017-12-01

Acute leukaemia (AL) is a critical neoplasm of white blood cells. Diagnosing AL requires bone marrow puncture procedure, which many patients do not consent to for it is invasive. Hence sensitive and specific early diagnostic biomarkers are essential for non-invasive diagnosis, new therapeutics and improving the disease prognosis. To differentiate the metabolic alterations associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), we investigated serum of ALL and AML patients in comparison with two controls using gas chromatography coupled with triple quadrupole tandem mass spectrometry and multivariate statistical analysis. Twenty seven out of 1425 metabolites were found differentiative among ALL, AML, aplastic anaemia (APA) patients and healthy control using p-value ≤ 0.001. ALL is the most dissimilar group from other three groups as in hierarchical clustering showed 72.1% dissimilarity. Model generation using PLSDA gave an overall accuracy of 91.9%. This study helps in metabolic fingerprinting of control and disease serum at high significance levels and could be used for early diagnosing of AL. Based on pathways analysis, fatty acid metabolism is deregulated in patients with AL and may represent an underlying metabolic pathway associated with disease progression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Functional metabolite assemblies—a review

NASA Astrophysics Data System (ADS)

Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

2018-05-01

Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

Nuclear magnetic relaxation induced by exchange-mediated orientational randomization: longitudinal relaxation dispersion for a dipole-coupled spin-1/2 pair.

PubMed

Chang, Zhiwei; Halle, Bertil

2013-10-14

In complex biological or colloidal samples, magnetic relaxation dispersion (MRD) experiments using the field-cycling technique can characterize molecular motions on time scales ranging from nanoseconds to microseconds, provided that a rigorous theory of nuclear spin relaxation is available. In gels, cross-linked proteins, and biological tissues, where an immobilized macromolecular component coexists with a mobile solvent phase, nuclear spins residing in solvent (or cosolvent) species relax predominantly via exchange-mediated orientational randomization (EMOR) of anisotropic nuclear (electric quadrupole or magnetic dipole) couplings. The physical or chemical exchange processes that dominate the MRD typically occur on a time scale of microseconds or longer, where the conventional perturbation theory of spin relaxation breaks down. There is thus a need for a more general relaxation theory. Such a theory, based on the stochastic Liouville equation (SLE) for the EMOR mechanism, is available for a single quadrupolar spin I = 1. Here, we present the corresponding theory for a dipole-coupled spin-1/2 pair. To our knowledge, this is the first treatment of dipolar MRD outside the motional-narrowing regime. Based on an analytical solution of the spatial part of the SLE, we show how the integral longitudinal relaxation rate can be computed efficiently. Both like and unlike spins, with selective or non-selective excitation, are treated. For the experimentally important dilute regime, where only a small fraction of the spin pairs are immobilized, we obtain simple analytical expressions for the auto-relaxation and cross-relaxation rates which generalize the well-known Solomon equations. These generalized results will be useful in biophysical studies, e.g., of intermittent protein dynamics. In addition, they represent a first step towards a rigorous theory of water (1)H relaxation in biological tissues, which is a prerequisite for unravelling the molecular basis of soft

Multi-region relaxed Hall magnetohydrodynamics with flow

DOE PAGES

Lingam, Manasvi; Abdelhamid, Hamdi M.; Hudson, Stuart R.

2016-08-03

The recent formulations of multi-region relaxed magnetohydrodynamics (MRxMHD) have generalized the famous Woltjer-Taylor states by incorporating a collection of “ideal barriers” that prevent global relaxation and flow. In this paper, we generalize MRxMHD with flow to include Hall effects, and thereby obtain the partially relaxed counterparts of the famous double Beltrami states as a special subset. The physical and mathematical consequences arising from the introduction of the Hall term are also presented. We demonstrate that our results (in the ideal MHD limit) constitute an important subset of ideal MHD equilibria, and we compare our approach against other variational principles proposedmore » for deriving the partially relaxed states.« less

Bimodal dielectric relaxation of electrolyte solutions in weakly polar solvents.

PubMed

Yamaguchi, Tsuyoshi; Koda, Shinobu

2014-12-28

The dielectric relaxation spectra of dilute electrolyte solutions in solvents of small dielectric constants are investigated both theoretically and experimentally. The theoretical calculation in our previous work [T. Yamaguchi, T. Matsuoka, and S. Koda, J. Chem. Phys. 135, 164511 (2011)] is reanalyzed, and it is shown that the dielectric relaxation spectra are composed of three components, namely, the relaxation of ionic atmosphere, the reorientational relaxation of ion pairs, and the collision between ions. The relaxation frequency of the slowest one increases with increasing the concentration, and the slower two relaxations, those of ionic atmosphere and ion pairs, merge into one at the concentration where the Debye length is comparable to the size of ions. Experimentally, the dielectric relaxation spectra of some electrolytes in two solvents, tetrahydrofuran and tetraglyme, are determined at frequencies from 300 kHz to 200 MHz, and the presence of the slower two relaxations was confirmed. The concentration dependence of the relaxation frequency is also in harmony with the theoretical calculation. The relationship between the dielectric relaxation spectra and the concentration dependence of the ionic conductivity is discussed.

Bimodal dielectric relaxation of electrolyte solutions in weakly polar solvents

NASA Astrophysics Data System (ADS)

Yamaguchi, Tsuyoshi; Koda, Shinobu

2014-12-01

The dielectric relaxation spectra of dilute electrolyte solutions in solvents of small dielectric constants are investigated both theoretically and experimentally. The theoretical calculation in our previous work [T. Yamaguchi, T. Matsuoka, and S. Koda, J. Chem. Phys. 135, 164511 (2011)] is reanalyzed, and it is shown that the dielectric relaxation spectra are composed of three components, namely, the relaxation of ionic atmosphere, the reorientational relaxation of ion pairs, and the collision between ions. The relaxation frequency of the slowest one increases with increasing the concentration, and the slower two relaxations, those of ionic atmosphere and ion pairs, merge into one at the concentration where the Debye length is comparable to the size of ions. Experimentally, the dielectric relaxation spectra of some electrolytes in two solvents, tetrahydrofuran and tetraglyme, are determined at frequencies from 300 kHz to 200 MHz, and the presence of the slower two relaxations was confirmed. The concentration dependence of the relaxation frequency is also in harmony with the theoretical calculation. The relationship between the dielectric relaxation spectra and the concentration dependence of the ionic conductivity is discussed.

Isothermal enthalpy relaxation of glassy 1,2,6-hexanetriol

NASA Astrophysics Data System (ADS)

Fransson, Å.; Bäckström, G.

The isothermal enthalpy relaxation of glassy 1,2,6-hexanetriol has been measured at six temperatures. The relaxation time and the distribution parameters extracted from fits of the Williams-Watts relaxation function are compared with parameters obtained by other techniques and on other substances. A detailed comparison of the Williams-Watts and the Davidson-Cole relaxation functions is presented.

The Efficacy of Relaxation Training in Treating Anxiety

ERIC Educational Resources Information Center

Francesco, Pagnini; Mauro, Manzoni Gian; Gianluca, Castelnuovo; Enrico, Molinari

2009-01-01

This paper provides a review of scientific literature about relaxation training and its effects on anxiety. Research investigating progressive relaxation, meditation, applied relaxation and autogenic training were considered. All these methods proved to be effective in reducing anxiety in all kind of samples, affected or not by physical or…

Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

PubMed

Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

2015-08-01

Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal.

Secondary Metabolites in Allergic Plant Pollen Samples Modulate Afferent Neurons and Murine Tracheal Rings.

PubMed

Božičević, Alen; De Mieri, Maria; Nassenstein, Christina; Wiegand, Silke; Hamburger, Matthias

2017-11-22

Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy. Polyamine conjugates, flavonoids, and sesquiterpene lactones were identified. Polyamine conjugates were characteristic of all Asteraceae species. The presence of sesquiterpene lactones in Asteraceae pollen varied between species and pollen lots. All plant pollen, including those from non-Asteraceae species, contained to some extent electrophiles as determined by their reaction with N-acetyl-l-cysteine. Selected pollen extracts and pure compounds were tested in murine afferent neurons and in murine tracheal preparations. Tetrahydrofuran extracts of Ambrosia artemisiifolia and Ambrosia psilostachya pollen and a mixture of sesquiterpene lactones coronopilin/parthenin increased the intracellular Ca 2+ concentration in 15%, 32%, and 37% of cinnamaldehyde-responsive neurons, respectively. In organ bath experiments, only the sesquiterpene lactones tested induced a weak dilatation of naïve tracheas and strongly lowered the maximal methacholine-induced tracheal constriction. A tetrahydrofuran extract of A. psilostachya and coronopilin/parthenin led to a time-dependent relaxation of the methacholine-preconstricted trachea. These results provide the first evidence for a potential role of pollen secondary metabolites in the modulation of the tracheal tone.

Relaxation dynamics of a multihierarchical polymer network

NASA Astrophysics Data System (ADS)

Jurjiu, Aurel; Biter, Teodor Lucian; Turcu, Flaviu

2017-01-01

In this work, we study the relaxation dynamics of a multihierarchical polymer network built by replicating the Vicsek fractal in dendrimer shape. The relaxation dynamics is investigated in the framework of the generalized Gaussian structure model by employing both Rouse and Zimm approaches. In the Rouse-type approach, we show the iterative procedure whereby the whole eigenvalue spectrum of the connectivity matrix of the multihierarchical structure can be obtained. Remarkably, the general picture that emerges from both approaches, even though we have a mixed growth algorithm, is that the obtained multihierarchical structure preserves the individual relaxation behaviors of its components. The theoretical findings with respect to the splitting of the intermediate domain of the relaxation quantities are well supported by experimental results.

Effects of water on the primary and secondary relaxation of xylitol and sorbitol: Implication on the origin of the Johari-Goldstein relaxation

NASA Astrophysics Data System (ADS)

Psurek, T.; Maslanka, S.; Paluch, M.; Nozaki, R.; Ngai, K. L.

2004-07-01

Dielectric spectroscopy was employed to study the effects of water on the primary α -relaxation and the secondary β -relaxation of xylitol. The measurements were made on anhydrous xylitol and mixtures of xylitol with water with three different water concentrations over a temperature range from 173K to 293K . The α -relaxation speeds up with increasing concentration of water in xylitol, whereas the rate of the β -relaxation is essentially unchanged. Some systematic differences in the behavior of α -relaxation for anhydrous xylitol and the mixtures were observed. Our findings confirm all the observations of Nozaki [R. Nozaki, H. Zenitani, A. Minoguchi, and K. Kitai, J. Non-Cryst. Solids 307, 349 (2002)] in sorbitol/water mixtures. Effects of water on both the α - and β -relaxation dynamics in xylitol and sorbitol are explained by using the coupling model.

Alpha3beta4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo

PubMed Central

McCallum, Sarah E.; Cowe, Matthew A.; Lewis, Samuel W.; Glick, Stanley D.

2012-01-01

Habenulo-interpeduncular nicotinic receptors, particularly those containing α3, β4 and α5 subunits, have recently been implicated in the reinforcing effects of nicotine. Our laboratory has shown that injection of α3β4 nicotinic receptor antagonists into the medial habenula (MHb) decreases self-administration of multiple abused drugs, including nicotine (Glick et al., 2006; 2008; 2011). However, it is unclear whether blockade of MHb nicotinic receptors has a direct effect on mesolimbic dopamine. Here, we performed in vivo microdialysis in female rats. Microdialysis probes were implanted into the nucleus accumbens (NAcc) and α3β4 nicotinic receptor antagonists (18-methoxycoronaridine; 18-MC or α-conotoxin AuIB; AuIB), were injected into the ipsilateral MHb, just prior to systemic nicotine (0.4 mg/kg, s.c.). Dialysate samples were collected before and after drug administration and levels of extracellular dopamine and its metabolites were measured using HPLC. Acute nicotine administration increased levels of extracellular dopamine and its metabolites in the NAcc. Pre-treatment with intra-habenular AuIB or 18-MC prevented nicotine-induced increases in accumbal dopamine. Neither drug had an effect on nicotine-induced increases in dopamine metabolites, suggesting that α3β4 receptors do not play a role in dopamine metabolism. The effect of intra-habenular blockade of α3β4 receptors on NAcc dopamine was selective for acute nicotine: neither AuIB nor 18-MC prevented increases in NAcc dopamine stimulated by acute d-amphetamine or morphine. These results suggest the mesolimbic response to acute nicotine, but not to acute administration of other drugs of abuse, is directly modulated by α3β4 nicotinic receptors in the MHb, and emphasize a critical role for habenular nicotinic receptors in nicotine’s reinforcing effects. PMID:22561751

46 CFR 46.10-1 - Relaxation from regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Relaxation from regulations. 46.10-1 Section 46.10-1... PASSENGER VESSELS Administration § 46.10-1 Relaxation from regulations. (a) New passenger vessels making... engaged in foreign voyages by sea may be permitted relaxation from the requirements of this part if, in...

46 CFR 46.10-1 - Relaxation from regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Relaxation from regulations. 46.10-1 Section 46.10-1... PASSENGER VESSELS Administration § 46.10-1 Relaxation from regulations. (a) New passenger vessels making... engaged in foreign voyages by sea may be permitted relaxation from the requirements of this part if, in...

Secondary metabolites in fungus-plant interactions

PubMed Central

Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

2015-01-01

Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

Magnetic resonance imaging relaxation time in Alzheimer's disease.

PubMed

Tang, Xiang; Cai, Feng; Ding, Dong-Xue; Zhang, Lu-Lu; Cai, Xiu-Ying; Fang, Qi

2018-05-05

The magnetic resonance imaging (MRI) relaxation time constants, T1 and T2, are sensitive to changes in brain tissue microstructure integrity. Quantitative T1 and T2 relaxation times have been proposed to serve as non-invasive biomarkers of Alzheimer's disease (AD), in which alterations are believed to not only reflect AD-related neuropathology but also cognitive impairment. In this review, we summarize the applications and key findings of MRI techniques in the context of both AD subjects and AD transgenic mouse models. Furthermore, the possible mechanisms of relaxation time alterations in AD will be discussed. Future studies could focus on relaxation time alterations in the early stage of AD, and longitudinal studies are needed to further explore relaxation time alterations during disease progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Interface roughness mediated phonon relaxation rates in Si quantum dots.

NASA Astrophysics Data System (ADS)

Ferdous, Rifat; Hsueh, Yuling; Klimeck, Gerhard; Rahman, Rajib

2015-03-01

Si QDs are promising candidates for solid-state quantum computing due to long spin coherence times. However, the valley degeneracy in Si adds an additional degree of freedom to the electronic structure. Although the valley and orbital indices can be uniquely identified in an ideal Si QD, interface roughness mixes valley and orbital states in realistic dots. Such valley-orbit coupling can strongly influence T1 times in Si QDs. Recent experimental measurements of various relaxation rates differ from previous predictions of phonon relaxation in ideal Si QDs. To understand how roughness affects different relaxation rates, for example spin relaxation due to spin-valley coupling, which is a byproduct of spin-orbit and valley-orbit coupling, we need to understand the effect of valley-orbit coupling on valley relaxation first. Using a full-band atomistic tight-binding description for both the system's electron and electron-phonon hamiltonian, we analyze the effect of atomic-scale interface disorder on phonon induced valley relaxation and spin relaxation in a Si QD. We find that, the valley splitting dependence of valley relaxation rate governs the magnetic field dependence of spin relaxation rate. Our results help understand experimentally measured relaxation times.

Metabolite damage and repair in metabolic engineering design.

PubMed

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Metabolite damage and repair in metabolic engineering design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields,more » and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.« less

Extended MHD Modeling of Tearing-Driven Magnetic Relaxation

NASA Astrophysics Data System (ADS)

Sauppe, Joshua

2016-10-01

Driven plasma pinch configurations are characterized by the gradual accumulation and episodic release of free energy in discrete relaxation events. The hallmark of this relaxation in a reversed-field pinch (RFP) plasma is flattening of the parallel current density profile effected by a fluctuation-induced dynamo emf in Ohm's law. Nonlinear two-fluid modeling of macroscopic RFP dynamics has shown appreciable coupling of magnetic relaxation and the evolution of plasma flow. Accurate modeling of RFP dynamics requires the Hall effect in Ohm's law as well as first order ion finite Larmor radius (FLR) effects, represented by the Braginskii ion gyroviscous stress tensor. New results find that the Hall dynamo effect from < J × B > / ne can counter the MHD effect from - < V × B > in some of the relaxation events. The MHD effect dominates these events and relaxes the current profile toward the Taylor state, but the opposition of the two dynamos generates plasma flow in the direction of equilibrium current density, consistent with experimental measurements. Detailed experimental measurements of the MHD and Hall emf terms are compared to these extended MHD predictions. Tracking the evolution of magnetic energy, helicity, and hybrid helicity during relaxation identifies the most important contributions in single-fluid and two-fluid models. Magnetic helicity is well conserved relative to the magnetic energy during relaxation. The hybrid helicity is dominated by magnetic helicity in realistic low-beta pinch conditions and is also well conserved. Differences of less than 1 % between magnetic helicity and hybrid helicity are observed with two-fluid modeling and result from cross helicity evolution through ion FLR effects, which have not been included in contemporary relaxation theories. The kinetic energy driven by relaxation in the computations is dominated by velocity components perpendicular to the magnetic field, an effect that had not been predicted. Work performed at

Dielectric relaxation of gamma irradiated muscovite mica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, Navjeet; Singh, Mohan, E-mail: mohansinghphysics@gmail.com; Singh, Lakhwant

2015-03-15

Highlights: • The present article reports the effect of gamma irradiation on the dielectric relaxation characteristics of muscovite mica. • Dielectric and electrical relaxations have been analyzed in the framework of dielectric permittivity, electric modulus and Cole–Cole formalisms. • The frequency dependent electrical conductivity has been rationalized using Johnsher’s universal power law. • The experimentally measured electric modulus and conductivity data have been fitted using Havriliak–Negami dielectric relaxation function. - Abstract: In the present research, the dielectric relaxation of gamma irradiated muscovite mica was studied in the frequency range of 0.1 Hz–10 MHz and temperature range of 653–853 K, usingmore » the dielectric permittivity, electric modulus and conductivity formalisms. The dielectric constants (ϵ′ and ϵ′′) are found to be high for gamma irradiated muscovite mica as compared to the pristine sample. The frequency dependence of the imaginary part of complex electric modulus (M′′) and dc conductivity data conforms Arrhenius law with single value of activation energy for pristine sample and two values of activation energy for gamma irradiated mica sample. The experimentally assessed electric modulus and conductivity information have been interpreted by the Havriliak–Negami dielectric relaxation explanation. Using the Cole–Cole framework, an analysis of real and imaginary characters of the electric modulus for pristine and gamma irradiated sample was executed which reflects the non-Debye relaxation mechanism.« less

Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized (1)H MRS study.

PubMed

Iltis, Isabelle; Koski, Dee M; Eberly, Lynn E; Nelson, Christopher D; Deelchand, Dinesh K; Valette, Julien; Ugurbil, Kamil; Lim, Kelvin O; Henry, Pierre-Gilles

2009-08-01

Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single-voxel (1)H-MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short-echo time sequence (STEAM) was used to acquire spectra in a 32-microL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre- vs. post-injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti-psychotic drugs in vivo. 2009 John Wiley & Sons, Ltd.

Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis.

PubMed

DeLuca, Jennifer Aa; Allred, Kimberly F; Menon, Rani; Riordan, Rebekah; Weeks, Brad R; Jayaraman, Arul; Allred, Clinton D

2018-06-01

Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut

Bayesian Modeling of NMR Data: Quantifying Longitudinal Relaxation in Vivo, and in Vitro with a Tissue-Water-Relaxation Mimic (Crosslinked Bovine Serum Albumin).

PubMed

Meinerz, Kelsey; Beeman, Scott C; Duan, Chong; Bretthorst, G Larry; Garbow, Joel R; Ackerman, Joseph J H

2018-01-01

Recently, a number of MRI protocols have been reported that seek to exploit the effect of dissolved oxygen (O 2 , paramagnetic) on the longitudinal 1 H relaxation of tissue water, thus providing image contrast related to tissue oxygen content. However, tissue water relaxation is dependent on a number of mechanisms, and this raises the issue of how best to model the relaxation data. This problem, the model selection problem, occurs in many branches of science and is optimally addressed by Bayesian probability theory. High signal-to-noise, densely sampled, longitudinal 1 H relaxation data were acquired from rat brain in vivo and from a cross-linked bovine serum albumin (xBSA) phantom, a sample that recapitulates the relaxation characteristics of tissue water in vivo . Bayesian-based model selection was applied to a cohort of five competing relaxation models: (i) monoexponential, (ii) stretched-exponential, (iii) biexponential, (iv) Gaussian (normal) R 1 -distribution, and (v) gamma R 1 -distribution. Bayesian joint analysis of multiple replicate datasets revealed that water relaxation of both the xBSA phantom and in vivo rat brain was best described by a biexponential model, while xBSA relaxation datasets truncated to remove evidence of the fast relaxation component were best modeled as a stretched exponential. In all cases, estimated model parameters were compared to the commonly used monoexponential model. Reducing the sampling density of the relaxation data and adding Gaussian-distributed noise served to simulate cases in which the data are acquisition-time or signal-to-noise restricted, respectively. As expected, reducing either the number of data points or the signal-to-noise increases the uncertainty in estimated parameters and, ultimately, reduces support for more complex relaxation models.

129 Xe NMR Relaxation-Based Macromolecular Sensing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomes, Muller D.; Dao, Phuong; Jeong, Keunhong

2016-07-29

A 129Xe NMR relaxation-based sensing approach is reported on that exploits changes in the bulk xenon relaxation rate induced by slowed tumbling of a cryptophane-based sensor upon target binding. The amplification afforded by detection of the bulk dissolved xenon allows sensitive detection of targets. The sensor comprises a xenon-binding cryptophane cage, a target interaction element, and a metal chelating agent. Xenon associated with the target-bound cryptophane cage is rapidly relaxed and then detected after exchange with the bulk. Here we show that large macromolecular targets increase the rotational correlation time of xenon, increasing its relaxation rate. Upon binding of amore » biotin-containing sensor to avidin at 1.5 μM concentration, the free xenon T 2 is reduced by a factor of 4.« less

Picosecond absorption relaxation measured with nanosecond laser photoacoustics.

PubMed

Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin; Wang, Lihong V

2010-10-18

Picosecond absorption relaxation-central to many disciplines-is typically measured by ultrafast (femtosecond or picosecond) pump-probe techniques, which however are restricted to optically thin and weakly scattering materials or require artificial sample preparation. Here, we developed a reflection-mode relaxation photoacoustic microscope based on a nanosecond laser and measured picosecond absorption relaxation times. The relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, were measured at 576 nm. The added advantages in dispersion susceptibility, laser-wavelength availability, reflection sensing, and expense foster the study of natural-including strongly scattering and nonfluorescent-materials.

Calorimetric and relaxation properties of xylitol-water mixtures

NASA Astrophysics Data System (ADS)

Elamin, Khalid; Sjöström, Johan; Jansson, Helén; Swenson, Jan

2012-03-01

We present the first broadband dielectric spectroscopy (BDS) and differential scanning calorimetry study of supercooled xylitol-water mixtures in the whole concentration range and in wide frequency (10-2-106 Hz) and temperature (120-365 K) ranges. The calorimetric glass transition, Tg, decreases from 247 K for pure xylitol to about 181 K at a water concentration of approximately 37 wt. %. At water concentrations in the range 29-35 wt. % a plentiful calorimetric behaviour is observed. In addition to the glass transition, almost simultaneous crystallization and melting events occurring around 230-240 K. At higher water concentrations ice is formed during cooling and the glass transition temperature increases to a steady value of about 200 K for all higher water concentrations. This Tg corresponds to an unfrozen xylitol-water solution containing 20 wt. % water. In addition to the true glass transition we also observed a glass transition-like feature at 220 K for all the ice containing samples. However, this feature is more likely due to ice dissolution [A. Inaba and O. Andersson, Thermochim. Acta, 461, 44 (2007)]. In the case of the BDS measurements the presence of water clearly has an effect on both the cooperative α-relaxation and the secondary β-relaxation. The α-relaxation shows a non-Arrhenius temperature dependence and becomes faster with increasing concentration of water. The fragility of the solutions, determined by the temperature dependence of the α-relaxation close to the dynamic glass transition, decreases with increasing water content up to about 26 wt. % water, where ice starts to form. This decrease in fragility with increasing water content is most likely caused by the increasing density of hydrogen bonds, forming a network-like structure in the deeply supercooled regime. The intensity of the secondary β-relaxation of xylitol decreases noticeably already at a water content of 2 wt. %, and at a water content above 5 wt. % it has been replaced by a

Vasodilating effect of norethisterone and its 5 alpha metabolites: a novel nongenomic action.

PubMed

Perusquía, Mercedes; Villalón, Carlos M; Navarrete, Erika; García, Gustavo A; Pérez-Palacios, Gregorio; Lemus, Ana E

2003-08-15

Estrogens are generally administered in hormone replacement therapy in combination with synthetic progestins. Studies of cardiovascular risk factors in postmenopausal women have shown a variety of responses according to the molecular structure of the progestin used in hormone replacement therapy schemes. The present study sets out to determine the vasoactive effects of norethisterone and its 5alpha-dihydro (5alpha-norethisterone) and -tetrahydro (3alpha,5alpha-norethisterone and 3beta,5alpha-norethisterone) metabolites in isolated precontracted rat thoracic aorta. The addition of norethisterone and 3alpha,5alpha-norethisterone in rat aorta exhibited a potent, concentration-response inhibition of noradrenaline-induced contraction, while 5alpha- and 3beta,5alpha-norethisterone had very little, if any, vasorelaxing effect. Relaxation to norethisterone and 3alpha,5alpha-norethisterone had very rapid time-courses and it was neither affected by the absence of endothelium nor by the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine methyl ester (L-NAME). The addition of specific anti-androgen, anti-progestin and anti-estrogen compounds and protein synthesis inhibitors did not preclude the vasorelaxing effect of norethisterone and its 3alpha,5alpha-reduced metabolite. The results strongly suggest that these effects are not mediated by nuclear sex steroid hormone receptors. The overall data document a novel nongenomic endothelium-independent vasorelaxing action of a 19-nor synthetic progestin and one of its A-ring-reduced derivatives.

The Unquiet State of Violent Relaxation

NASA Astrophysics Data System (ADS)

Henriksen, Richard

2005-08-01

In 1967 Lynden-Bell presented a statistical mechanical theory for the relaxation of collisionless systems. Since then this theory has been studied numerically and theoretically by many authors. Nakamura in 2000 gave an alternate theory that differed from that of Lynden- Bell by predicting a Gaussian equilibrium distribution function rather than Fermi-Dirac. More recently Henriksen in 2004 has used a coarsegraining technique on cosmological infall systems that also predicts a Gaussian equilibrium distribution function. These relaxed states are thought to occur from the centre of the system outwards. Simulations of cosmological cold dark-matter halos however persist in finding central density cusps (the NFWprofile), which are inconsistent with the predicted distribution functions and perhaps with the observations of some galaxies. Some numerical studies (e.g.Merrall & Henriksen 2003) that attempt to measure the distribution function of dark matter do find Gaussian functions, provided that the initial asymmetry is not too great. Moreover recent work at Queen's reported here by MacMillan, suggests that it is the growth of asymmetry during the infall that produces the cusped behaviour. So put briefly, the essential physics of dark-matter relaxation remains "obscure" as does the validity of the theoretical predictions. "Violent virialization" occurs rapidly, well before subscale relaxation, but the scale at which the relaxation stops (and why) remains unclear. I will present some results that argue for wave-particle relaxation (Landau damping as frequently suggested by Kandrup) and in addition I will suggest that the evolution of isolated systems is very different from that of systems constantly disturbed by infall. Isolated systems may become trapped in an unrelaxed state by the development or existence of multipolar internal structure. Nevertheless a suitable coarse graining of the system may restore the predicted distribution functions.

[Molecular regulation of microbial secondary metabolites--a review].

PubMed

Wang, Linqi; Tan, Huarong

2009-04-01

Microbial secondary metabolites play an important role in the field of industry, agriculture, medicine and human health. The molecular regulation of secondary metabolites is gradually becoming noticeable and intriguing. In recent years, many researches have demonstrated that secondary metabolite biosynthesis is tightly linked to the physiological and developmental status in its producer. It is suggested that the biosynthesis of secondary metabolites involves in complex process concerning multi-level regulation. Here we reviewed the recent research progress on the molecular regulation of secondary metabolites in microorganisms. In known about ten thousand kinds of natural secondary metabolites, most of them (about 60%) were produced by Streptomycete. Therefore, the regulation of secondary metabolites in Streptomyces is chosen as the mainline in this review. Additionally, several well-studied antibiotics as the representative members were targeted. Finally, some suggestions, in response to the issues at present, have been presented in this paper.

Relaxing music counters heightened consolidation of emotional memory.

PubMed

Rickard, Nikki S; Wong, Wendy Wing; Velik, Lauren

2012-02-01

Emotional events tend to be retained more strongly than other everyday occurrences, a phenomenon partially regulated by the neuromodulatory effects of arousal. Two experiments demonstrated the use of relaxing music as a means of reducing arousal levels, thereby challenging heightened long-term recall of an emotional story. In Experiment 1, participants (N=84) viewed a slideshow, during which they listened to either an emotional or neutral narration, and were exposed to relaxing or no music. Retention was tested 1 week later via a forced choice recognition test. Retention for both the emotional content (Phase 2 of the story) and material presented immediately after the emotional content (Phase 3) was enhanced, when compared with retention for the neutral story. Relaxing music prevented the enhancement for material presented after the emotional content (Phase 3). Experiment 2 (N=159) provided further support to the neuromodulatory effect of music by post-event presentation of both relaxing music and non-relaxing auditory stimuli (arousing music/background sound). Free recall of the story was assessed immediately afterwards and 1 week later. Relaxing music significantly reduced recall of the emotional story (Phase 2). The findings provide further insight into the capacity of relaxing music to attenuate the strength of emotional memory, offering support for the therapeutic use of music for such purposes. Copyright © 2011 Elsevier Inc. All rights reserved.

Ultrafast energy relaxation in single light-harvesting complexes.

PubMed

Malý, Pavel; Gruber, J Michael; Cogdell, Richard J; Mančal, Tomáš; van Grondelle, Rienk

2016-03-15

Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub-100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump-probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changes in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations.

Secondary metabolites from Ganoderma.

PubMed

Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

2015-06-01

Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of choline on blood metabolites associated with lipid metabolism and digestion by steers fed corn-based diets.

PubMed

Bindel, D J; Titgemeyer, E C; Drouillard, J S; Ives, S E

2005-07-01

Ruminally cannulated steers (281 +/- 18 kg) were used to evaluate effects of choline on digestion and metabolism. Four steers were implanted with 24 mg of estradiol and 120 mg of trenbolone acetate, and four steers were not implanted. Cattle were assigned to concurrent 4 x 4 Latin squares. Dietary treatments were a 2 x 2 factorial: 0 or 4% tallow (DM basis) in corn-based diets, and 0 or 5 g/d supplemental choline administered abomasally. Blood collected before and 6 h after the initial choline infusion was used to assess acute responses to choline. Digestibility and blood metabolites were measured after adaptation to choline, as well as after an abomasal dose of 100 g of lipid. Digestibilities of dietary DM (P = 0.29) and of dietary total fatty acids (P = 0.42) were not affected by choline. Apparent digestibilities of C18:0 and C18:1 fatty acids were greater (P < 0.05) when diets contained 4% tallow. Digestibilities of fatty acids in the lipid dose were less than those in the diet, and no biologically important differences in fatty acid disappearance resulted from the treatments. No significant acute responses to choline were detected. After adaptation to choline, no important differences in plasma metabolites occurred in response to choline infusion. Plasma urea was less (P < 0.05) for implanted cattle, reflecting increased deposition of protein. Plasma cholesterol was greater (P < 0.05) for steers fed 4% tallow. Changes in plasma triglycerides in response to an abomasal lipid dose were less (P < 0.05) for steers fed 4% tallow, probably due to greater triglyceride concentrations at the time of lipid dosing. In summary, few responses to abomasally infused choline were observed in either digestion or plasma metabolites.

Relaxation as a Factor in Semantic Desensitization

ERIC Educational Resources Information Center

Bechtel, James E.; McNamara, J. Regis

1975-01-01

Relaxation and semantic desensitization were used to alleviate the fear of phobic females. Results showed that semantic desensitization, alone or in combination with relaxation, failed to modify the evaluative meanings evoked by the feared object. (SE)

Nuclear spin-lattice relaxation in nitroxide spin-label EPR.

PubMed

Marsh, Derek

2016-11-01

Nuclear relaxation is a sensitive monitor of rotational dynamics in spin-label EPR. It also contributes competing saturation transfer pathways in T 1 -exchange spectroscopy, and the determination of paramagnetic relaxation enhancement in site-directed spin labelling. A survey shows that the definition of nitrogen nuclear relaxation rate W n commonly used in the CW-EPR literature for 14 N-nitroxyl spin labels is inconsistent with that currently adopted in time-resolved EPR measurements of saturation recovery. Redefinition of the normalised 14 N spin-lattice relaxation rate, b=W n /(2W e ), preserves the expressions used for CW-EPR, whilst rendering them consistent with expressions for saturation recovery rates in pulsed EPR. Furthermore, values routinely quoted for nuclear relaxation times that are deduced from EPR spectral diffusion rates in 14 N-nitroxyl spin labels do not accord with conventional analysis of spin-lattice relaxation in this three-level system. Expressions for CW-saturation EPR with the revised definitions are summarised. Data on nitrogen nuclear spin-lattice relaxation times are compiled according to the three-level scheme for 14 N-relaxation: T 1 n =1/W n . Results are compared and contrasted with those for the two-level 15 N-nitroxide system. Copyright © 2016 Elsevier Inc. All rights reserved.

Definition, evaluation, and management of brain relaxation during craniotomy.

PubMed

Li, J; Gelb, A W; Flexman, A M; Ji, F; Meng, L

2016-06-01

The term 'brain relaxation' is routinely used to describe the size and firmness of the brain tissue during craniotomy. The status of brain relaxation is an important aspect of neuroanaesthesia practice and is relevant to the operating conditions, retraction injury, and likely patient outcomes. Brain relaxation is determined by the relationship between the volume of the intracranial contents and the capacity of the intracranial space (i.e. a content-space relationship). It is a concept related to, but distinct from, intracranial pressure. The evaluation of brain relaxation should be standardized to facilitate clinical communication and research collaboration. Both advantageous and disadvantageous effects of the various interventions for brain relaxation should be taken into account in patient care. The outcomes that matter the most to patients should be emphasized in defining, evaluating, and managing brain relaxation. To date, brain relaxation has not been reviewed specifically, and the aim of this manuscript is to discuss the current approaches to the definition, evaluation, and management of brain relaxation, knowledge gaps, and targets for future research. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

PubMed

Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

2017-06-01

Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Occurrence of Pre- and Post-Harvest Mycotoxins and Other Secondary Metabolites in Danish Maize Silage

PubMed Central

Storm, Ida M. L. Drejer; Rasmussen, Rie Romme; Rasmussen, Peter Have

2014-01-01

Maize silage is a widely used feed product for cattle worldwide, which may be contaminated with mycotoxins, pre- and post-harvest. This concerns both farmers and consumers. To assess the exposure of Danish cattle to mycotoxins from maize silage, 99 samples of whole-crop maize (ensiled and un-ensiled) were analyzed for their contents of 27 mycotoxins and other secondary fungal metabolites by liquid chromatography-tandem mass spectrometry. The method specifically targets the majority of common pre- and post-harvest fungi associated with maize silage in Denmark. Sixty-one samples contained one or more of the 27 analytes in detectable concentrations. The most common mycotoxins were zearalenone, enniatin B nivalenol and andrastin A, found in 34%, 28%, 16% and 15% of the samples, respectively. None of the samples contained mycotoxins above the EU recommended maximum concentrations for Fusarium toxins in cereal-based roughage. Thus, the present study does not indicate that Danish maize silage in general is a cause of acute single mycotoxin intoxications in cattle. However, 31 of the samples contained multiple analytes; two samples as much as seven different fungal metabolites. Feed rations with maize silage may therefore contain complex mixtures of fungal secondary metabolites with unknown biological activity. This emphasizes the need for a thorough examination of the effects of chronic exposure and possible synergistic effects. PMID:25089350

Repeatability and reliability of muscle relaxation properties induced by motor cortical stimulation.

PubMed

Molenaar, Joery P; Voermans, Nicol C; de Jong, Lysanne A; Stegeman, Dick F; Doorduin, Jonne; van Engelen, Baziel G

2018-03-15

Impaired muscle relaxation is a feature of many neuromuscular disorders. However, there are few tests available to quantify muscle relaxation. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly inhibiting corticospinal drive. The aim of our study is to investigate if repeatability and reliability of TMS-induced relaxation is greater than voluntary relaxation. Furthermore, effects of sex, cooling and fatigue on muscle relaxation properties were studied. Muscle relaxation of deep finger flexors was assessed in twenty-five healthy subjects (14 M and 11 F, aged 39.1{plus minus}12.7 and 45.3{plus minus}8.7 years old, respectively) using handgrip dynamometry. All outcome measures showed greater repeatability and reliability in TMS-induced relaxation compared to voluntary relaxation. The within-subject coefficient of variability of normalized peak relaxation rate was lower in TMS-induced relaxation than in voluntary relaxation (3.0 vs 19.7% in men, and 6.1 vs 14.3% in women). The repeatability coefficient was lower (1.3 vs 6.1 s -1 in men and 2.3 vs 3.1 s -1 in women), and the intraclass correlation coefficient was higher (0.95 vs 0.53 in men and 0.78 vs 0.69 in women), for TMS-induced relaxation compared to voluntary relaxation. TMS enabled to demonstrate slowing effects of sex, muscle cooling, and muscle fatigue on relaxation properties that voluntary relaxation could not. In conclusion, repeatability and reliability of TMS-induced muscle relaxation was greater compared to voluntary muscle relaxation. TMS-induced muscle relaxation has the potential to be used in clinical practice for diagnostic purposes and therapy effect monitoring in patients with impaired muscle relaxation.

Relaxation-optimized transfer of spin order in Ising spin chains

NASA Astrophysics Data System (ADS)

Stefanatos, Dionisis; Glaser, Steffen J.; Khaneja, Navin

2005-12-01

In this paper, we present relaxation optimized methods for the transfer of bilinear spin correlations along Ising spin chains. These relaxation optimized methods can be used as a building block for the transfer of polarization between distant spins on a spin chain, a problem that is ubiquitous in multidimensional nuclear magnetic resonance spectroscopy of proteins. Compared to standard techniques, significant reduction in relaxation losses is achieved by these optimized methods when transverse relaxation rates are much larger than the longitudinal relaxation rates and comparable to couplings between spins. We derive an upper bound on the efficiency of the transfer of the spin order along a chain of spins in the presence of relaxation and show that this bound can be approached by the relaxation optimized pulse sequences presented in the paper.

Rounded stretched exponential for time relaxation functions.

PubMed

Powles, J G; Heyes, D M; Rickayzen, G; Evans, W A B

2009-12-07

A rounded stretched exponential function is introduced, C(t)=exp{(tau(0)/tau(E))(beta)[1-(1+(t/tau(0))(2))(beta/2)]}, where t is time, and tau(0) and tau(E) are two relaxation times. This expression can be used to represent the relaxation function of many real dynamical processes, as at long times, t>tau(0), the function converges to a stretched exponential with normalizing relaxation time, tau(E), yet its expansion is even or symmetric in time, which is a statistical mechanical requirement. This expression fits well the shear stress relaxation function for model soft soft-sphere fluids near coexistence, with tau(E)relaxation (both the modulus and viscosity forms). It is shown that both the dielectric spectra and dynamic shear modulus imaginary parts approach the real axis with a slope equal to 0 at high frequency, whereas the dynamic viscosity has an infinite slope in the same limit. This indicates that inertial effects at high frequency are best discerned in the modulus rather than the viscosity Cole-Cole plot. As a consequence of the even expansion in time of the shear stress relaxation function, the value of the storage modulus derived from it at very high frequency exceeds that in the infinite frequency limit (i.e., G(infinity)).

Nitric oxide metabolites as biomarkers for influenza-like acute respiratory infections presenting to the emergency room.

PubMed

Mian, Asad I; Laham, Federico R; Cruz, Andrea T; Garg, Harsha; Macias, Charles G; Caviness, A Chantal; Piedra, Pedro A

2012-01-01

Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic. Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR. Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002). Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner.

Weak nanoscale chaos and anomalous relaxation in DNA

NASA Astrophysics Data System (ADS)

Mazur, Alexey K.

2017-06-01

Anomalous nonexponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack. To this end, the earlier computational approach in combination with an analytical theory is applied to the experimental DNA fragment. It is found that the intensity of breathing dynamics is strongly increased in the internal base pairs that flank the photoprobe, with anomalous relaxation quantitatively close to that in terminal base pairs. A physical mechanism is proposed to explain the coupling between the relaxation of base-pair breathing and the experimental response signal. It is concluded that the algebraic relaxation observed experimentally is very likely a manifestation of weakly chaotic dynamics of hydrogen-bond breathing in the base pairs stacked to the photoprobe and that the weak nanoscale chaos can represent an ubiquitous hidden source of nonexponential relaxation in ultrafast spectroscopy.

Weak nanoscale chaos and anomalous relaxation in DNA.

PubMed

Mazur, Alexey K

2017-06-01

Anomalous nonexponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack. To this end, the earlier computational approach in combination with an analytical theory is applied to the experimental DNA fragment. It is found that the intensity of breathing dynamics is strongly increased in the internal base pairs that flank the photoprobe, with anomalous relaxation quantitatively close to that in terminal base pairs. A physical mechanism is proposed to explain the coupling between the relaxation of base-pair breathing and the experimental response signal. It is concluded that the algebraic relaxation observed experimentally is very likely a manifestation of weakly chaotic dynamics of hydrogen-bond breathing in the base pairs stacked to the photoprobe and that the weak nanoscale chaos can represent an ubiquitous hidden source of nonexponential relaxation in ultrafast spectroscopy.

Load relaxation of olivine single crystals

NASA Astrophysics Data System (ADS)

Cooper, Reid F.; Stone, Donald S.; Plookphol, Thawatchai

2016-10-01

Single crystals of ferromagnesian olivine (San Carlos, AZ, peridot; Fo88-90) have been deformed in both uniaxial creep and load relaxation under conditions of ambient pressure, T = 1500°C and pO2 = 10-10 atm; creep stresses were in the range 40 ≤ σ1 (MPa) ≤ 220. The crystals were oriented such that the applied stress was parallel to [011]c, which promotes single slip on the slowest slip system in olivine, (010)[001]. The creep rates at steady state match well the results of earlier investigators, as does the stress sensitivity (a power law exponent of n = 3.6). Dislocation microstructures, including spatial distribution of low-angle (subgrain) boundaries, additionally confirm previous investigations. Inverted primary creep (an accelerating strain rate with an increase in stress) was observed. Load relaxation, however, produced a singular response—a single hardness curve—regardless of the magnitude of creep stress or total accumulated strain preceding relaxation. The log stress versus log strain rate data from load-relaxation and creep experiments overlap to within experimental error. The load-relaxation behavior is distinctly different than that described for other crystalline solids, where the flow stress is affected strongly by work hardening such that a family of distinct hardness curves is generated, which are related by a scaling function. The response of olivine for the conditions studied, we argue, indicates flow that is rate limited by dislocation glide, reflecting specifically a high intrinsic lattice resistance (Peierls stress).

Load Relaxation of Olivine Single Crystals

NASA Astrophysics Data System (ADS)

Cooper, R. F.; Stone, D. S.; Plookphol, T.

2016-12-01

Single crystals of ferromagnesian olivine (San Carlos, AZ, peridot; Fo90-92) have been deformed in both uniaxial creep and load relaxation under conditions of ambient pressure, T = 1500ºC and pO2 = 10-10 atm; creep stresses were in the range 40 ≤ σ1 (MPa) ≤ 220. The crystals were oriented such that the applied stress was parallel to [011]c, which promotes single slip on the slowest slip system in olivine, (010)[001]. The creep rates at steady state match well the results of earlier investigators, as does the stress sensitivity (a power-law exponent of n = 3.6). Dislocation microstructures, including spatial distribution of low-angle (subgrain) boundaries, additionally confirm previous investigations. Inverted primary creep (an accelerating strain rate with an increase in stress) was observed. Load-relaxation, however, produced a singular response—a single hardness curve—regardless of the magnitude of creep stress or total accumulated strain preceding relaxation. The log-stress v. log-strain rate data from load-relaxation and creep experiments overlap to within experimental error. The load-relaxation behavior is distinctly different that that described for other crystalline solids, where the flow stress is affected strongly by work hardening such that a family of distinct hardness curves is generated, which are related by a scaling function. The response of olivine for the conditions studied, thus, indicates flow that is rate-limited by dislocation glide, reflecting specifically a high intrinsic lattice resistance (Peierls stress).

Ultraslow dielectric relaxation process in supercooled polyhydric alcohols

NASA Astrophysics Data System (ADS)

Yomogida, Yoshiki; Minoguchi, Ayumi; Nozaki, Ryusuke

2006-04-01

Complex permittivity was obtained on glycerol, xylitol, sorbitol and sorbitol-xylitol mixtures in the supercooled liquid state in the frequency range between 10μHz and 500MHz at temperatures near and above the glass transition temperature. For all the materials, a dielectric relaxation process was observed in addition to the well-known structural α and Johari-Goldstein β relaxation process [G. P. Johari and M. Goldstein, J. Chem. Phys. 53, 2372 (1970)]. The relaxation time for the new process is always larger than that for the α process. The relaxation time shows non-Arrhenius temperature dependence with correlation to the behavior of the α process and it depends on the molecular size systematically. The dielectric relaxation strength for the new process shows the effect of thermal history and decreases exponentially with time at a constant temperature. It can be considered that a nonequilibrium dynamics causes the new process.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus

PubMed Central

Zawaski, Janice A.; Sahnoune, Iman

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT. PMID:27242931

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

PubMed

Rodgers, Shaefali P; Zawaski, Janice A; Sahnoune, Iman; Leasure, J Leigh; Gaber, M Waleed

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

Antifungal activity of microbial secondary metabolites.

PubMed

Coleman, Jeffrey J; Ghosh, Suman; Okoli, Ikechukwu; Mylonakis, Eleftherios

2011-01-01

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi.

Antifungal Activity of Microbial Secondary Metabolites

PubMed Central

Okoli, Ikechukwu; Mylonakis, Eleftherios

2011-01-01

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi. PMID:21966496

Relaxation-phenomena in LiAl/FeS-cells

NASA Astrophysics Data System (ADS)

Borger, W.; Kappus, W.; Panesar, H. S.

A theoretical model of the capacity of strongly relaxing electrochemical systems is applied to the LiAl/FeS system. Relaxation phenomena in LiAl and FeS electrodes can be described by this model. Experimental relaxation data indicate that lithium transport through the alpha-LiAl layer to the particle surface is the capacity limiting process at high discharge current density in the LiAl electrode in LiCl-KCl and LiF-LiCl-LiBr mixtures. Strong relaxation is observed in the FeS electrode with LiCl-KCl electrolyte caused by lithium concentration gradients and precipitation of KCl in the pores.

Developing a Learning Algorithm-Generated Empirical Relaxer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, Wayne; Kallman, Josh; Toreja, Allen

2016-03-30

One of the main difficulties when running Arbitrary Lagrangian-Eulerian (ALE) simulations is determining how much to relax the mesh during the Eulerian step. This determination is currently made by the user on a simulation-by-simulation basis. We present a Learning Algorithm-Generated Empirical Relaxer (LAGER) which uses a regressive random forest algorithm to automate this decision process. We also demonstrate that LAGER successfully relaxes a variety of test problems, maintains simulation accuracy, and has the potential to significantly decrease both the person-hours and computational hours needed to run a successful ALE simulation.

Escape time, relaxation, and sticky states of a softened Henon-Heiles model: Low-frequency vibrational mode effects and glass relaxation

NASA Astrophysics Data System (ADS)

Toledo-Marín, J. Quetzalcóatl; Naumis, Gerardo G.

2018-04-01

Here we study the relaxation of a chain consisting of three masses joined by nonlinear springs and periodic conditions when the stiffness is weakened. This system, when expressed in their normal coordinates, yields a softened Henon-Heiles system. By reducing the stiffness of one low-frequency vibrational mode, a faster relaxation is enabled. This is due to a reduction of the energy barrier heights along the softened normal mode as well as for a widening of the opening channels of the energy landscape in configurational space. The relaxation is for the most part exponential, and can be explained by a simple flux equation. Yet, for some initial conditions the relaxation follows as a power law, and in many cases there is a regime change from exponential to power-law decay. We pinpoint the initial conditions for the power-law decay, finding two regions of sticky states. For such states, quasiperiodic orbits are found since almost for all components of the initial momentum orientation, the system is trapped inside two pockets of configurational space. The softened Henon-Heiles model presented here is intended as the simplest model in order to understand the interplay of rigidity, nonlinear interactions and relaxation for nonequilibrium systems such as glass-forming melts or soft matter. Our softened system can be applied to model β relaxation in glasses and suggest that local reorientational jumps can have an exponential and a nonexponential contribution for relaxation, the latter due to asymmetric molecules sticking in cages for certain orientations.

Gaussian signal relaxation around spin echoes: Implications for precise reversible transverse relaxation quantification of pulmonary tissue at 1.5 and 3 Tesla.

PubMed

Zapp, Jascha; Domsch, Sebastian; Weingärtner, Sebastian; Schad, Lothar R

2017-05-01

To characterize the reversible transverse relaxation in pulmonary tissue and to study the benefit of a quadratic exponential (Gaussian) model over the commonly used linear exponential model for increased quantification precision. A point-resolved spectroscopy sequence was used for comprehensive sampling of the relaxation around spin echoes. Measurements were performed in an ex vivo tissue sample and in healthy volunteers at 1.5 Tesla (T) and 3 T. The goodness of fit using χred2 and the precision of the fitted relaxation time by means of its confidence interval were compared between the two relaxation models. The Gaussian model provides enhanced descriptions of pulmonary relaxation with lower χred2 by average factors of 4 ex vivo and 3 in volunteers. The Gaussian model indicates higher sensitivity to tissue structure alteration with increased precision of reversible transverse relaxation time measurements also by average factors of 4 ex vivo and 3 in volunteers. The mean relaxation times of the Gaussian model in volunteers are T2,G' = (1.97 ± 0.27) msec at 1.5 T and T2,G' = (0.83 ± 0.21) msec at 3 T. Pulmonary signal relaxation was found to be accurately modeled as Gaussian, providing a potential biomarker T2,G' with high sensitivity. Magn Reson Med 77:1938-1945, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Milrinone Relaxes Pulmonary Veins in Guinea Pigs and Humans

PubMed Central

Rieg, Annette D.; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W.; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

2014-01-01

Introduction The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Material and Methods Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). Results In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of KATP-, BKCa 2+- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Discussion Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on KATP-, BKCa 2+- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease. PMID:24498166

Milrinone relaxes pulmonary veins in guinea pigs and humans.

PubMed

Rieg, Annette D; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

2014-01-01

The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+)- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+)- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

Modelling the acid/base 1H NMR chemical shift limits of metabolites in human urine.

PubMed

Tredwell, Gregory D; Bundy, Jacob G; De Iorio, Maria; Ebbels, Timothy M D

2016-01-01

Despite the use of buffering agents the 1 H NMR spectra of biofluid samples in metabolic profiling investigations typically suffer from extensive peak frequency shifting between spectra. These chemical shift changes are mainly due to differences in pH and divalent metal ion concentrations between the samples. This frequency shifting results in a correspondence problem: it can be hard to register the same peak as belonging to the same molecule across multiple samples. The problem is especially acute for urine, which can have a wide range of ionic concentrations between different samples. To investigate the acid, base and metal ion dependent 1 H NMR chemical shift variations and limits of the main metabolites in a complex biological mixture. Urine samples from five different individuals were collected and pooled, and pre-treated with Chelex-100 ion exchange resin. Urine samples were either treated with either HCl or NaOH, or were supplemented with various concentrations of CaCl 2 , MgCl 2 , NaCl or KCl, and their 1 H NMR spectra were acquired. Nonlinear fitting was used to derive acid dissociation constants and acid and base chemical shift limits for peaks from 33 identified metabolites. Peak pH titration curves for a further 65 unidentified peaks were also obtained for future reference. Furthermore, the peak variations induced by the main metal ions present in urine, Na + , K + , Ca 2+ and Mg 2+ , were also measured. These data will be a valuable resource for 1 H NMR metabolite profiling experiments and for the development of automated metabolite alignment and identification algorithms for 1 H NMR spectra.

Multiscale Relaxation Dynamics in Ultrathin Metallic Glass-Forming Films

NASA Astrophysics Data System (ADS)

Bi, Q. L.; Lü, Y. J.; Wang, W. H.

2018-04-01

The density layering phenomenon originating from a free surface gives rise to the layerlike dynamics and stress heterogeneity in ultrathin Cu-Zr glassy films, which facilitates the occurrence of multistep relaxations in the timescale of computer simulations. Taking advantage of this condition, we trace the relaxation decoupling and evolution with temperature simply via the intermediate scattering function. We show that the β relaxation hierarchically follows fast and slow modes in films, and there is a β -relaxation transition as the film is cooled close to the glass transition. We provide the direct observation of particle motions responsible for the β relaxation and reveal the dominant mechanism varying from the thermal activated to the cooperative jumps across the transition.

Stress Relaxation in Tensile Deformation of 304 Stainless Steel

NASA Astrophysics Data System (ADS)

Li, Xifeng; Li, Jiaojiao; Ding, Wei; Zhao, Shuangjun; Chen, Jun

2017-02-01

Improved ductility by stress relaxation has been reported in different kinds of steels. The influence of stress relaxation and its parameters on the ductility of 304 stainless steel has not been established so far. Stress relaxation behavior during tensile tests at different strain rates is studied in 304 stainless steel. It is observed that stress relaxation can obviously increase the elongation of 304 stainless steel in all cases. The elongation improvement of interrupted tension reaches to 14.9% compared with monotonic tension at 0.05 s-1. Contradicting with the published results, stress drop during stress relaxation increases with strain at all strain rates. It is related with dislocation motion velocity variation and martensitic transformation.

Relaxed Poisson cure rate models.

PubMed

Rodrigues, Josemar; Cordeiro, Gauss M; Cancho, Vicente G; Balakrishnan, N

2016-03-01

The purpose of this article is to make the standard promotion cure rate model (Yakovlev and Tsodikov, ) more flexible by assuming that the number of lesions or altered cells after a treatment follows a fractional Poisson distribution (Laskin, ). It is proved that the well-known Mittag-Leffler relaxation function (Berberan-Santos, ) is a simple way to obtain a new cure rate model that is a compromise between the promotion and geometric cure rate models allowing for superdispersion. So, the relaxed cure rate model developed here can be considered as a natural and less restrictive extension of the popular Poisson cure rate model at the cost of an additional parameter, but a competitor to negative-binomial cure rate models (Rodrigues et al., ). Some mathematical properties of a proper relaxed Poisson density are explored. A simulation study and an illustration of the proposed cure rate model from the Bayesian point of view are finally presented. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultrafast energy relaxation in single light-harvesting complexes

DOE PAGES

Maly, Pavel; Gruber, J. Michael; Cogdell, Richard J.; ...

2016-02-22

Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub–100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump–probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changesmore » in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Lastly, our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations.« less

Ultrafast energy relaxation in single light-harvesting complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maly, Pavel; Gruber, J. Michael; Cogdell, Richard J.

Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub–100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump–probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changesmore » in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Lastly, our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations.« less

Dielectric relaxation of high-k oxides

PubMed Central

2013-01-01

Frequency dispersion of high-k dielectrics was observed and classified into two parts: extrinsic cause and intrinsic cause. Frequency dependence of dielectric constant (dielectric relaxation), that is the intrinsic frequency dispersion, could not be characterized before considering the effects of extrinsic frequency dispersion. Several mathematical models were discussed to describe the dielectric relaxation of high-k dielectrics. For the physical mechanism, dielectric relaxation was found to be related to the degree of polarization, which depended on the structure of the high-k material. It was attributed to the enhancement of the correlations among polar nanodomain. The effect of grain size for the high-k materials' structure mainly originated from higher surface stress in smaller grain due to its higher concentration of grain boundary. PMID:24180696

Yeast synthetic biology for high-value metabolites.

PubMed

Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

2015-02-01

Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

The effects of music relaxation and muscle relaxation techniques on sleep quality and emotional measures among individuals with posttraumatic stress disorder

PubMed Central

Blanaru, Monica; Bloch, Boaz; Vadas, Limor; Arnon, Zahi; Ziv, Naomi; Kremer, Ilana; Haimov, Iris

2012-01-01

Posttraumatic stress disorder (PTSD), an anxiety disorder with lifetime prevalence of 7.8%, is characterized by symptoms that develop following exposure to traumatic life events and that cause an immediate experience of intense fear, helplessness or horror. PTSD is marked by recurrent nightmares typified by the recall of intrusive experiences and by extended disturbance throughout sleep. Individuals with PTSD respond poorly to drug treatments for insomnia. The disadvantages of drug treatment for insomnia underline the importance of non-pharmacological alternatives. Thus, the present study had three aims: first, to compare the efficiency of two relaxation techniques (muscular relaxation and progressive music relaxation) in alleviating insomnia among individuals with PTSD using both objective and subjective measures of sleep quality; second, to examine whether these two techniques have different effects on psychological indicators of PTSD, such as depression and anxiety; and finally, to examine how initial PTSD symptom severity and baseline emotional measures are related to the efficiency of these two relaxation methods. Thirteen PTSD patients with no other major psychiatric or neurological disorders participated in the study. The study comprised one seven-day running-in, no-treatment period, followed by two seven-day experimental periods. The treatments constituted either music relaxation or muscle relaxation techniques at desired bedtime. These treatments were randomly assigned. During each of these three experimental periods, subjects' sleep was continuously monitored with a wrist actigraph (Ambulatory Monitoring, Inc.), and subjects were asked to fill out several questionnaires concerned with a wide spectrum of issues, such as sleep, depression, and anxiety. Analyses revealed a significant increase in objective and subjective sleep efficiency and a significant reduction in depression level following music relaxation. Moreover, following music relaxation, a highly

Electron-impact vibrational relaxation in high-temperature nitrogen

NASA Technical Reports Server (NTRS)

Lee, Jong-Hun

1992-01-01

Vibrational relaxation process of N2 molecules by electron-impact is examined for the future planetary entry environments. Multiple-quantum transitions from excited states to higher/lower states are considered for the electronic ground state of the nitrogen molecule N2 (X 1Sigma-g(+)). Vibrational excitation and deexcitation rate coefficients obtained by computational quantum chemistry are incorporated into the 'diffusion model' to evaluate the time variations of vibrational number densities of each energy state and total vibrational energy. Results show a non-Boltzmann distribution of number densities at the earlier stage of relaxation, which in turn suppresses the equilibrium process but affects little the time variation of total vibrational energy. An approximate rate equation and a corresponding relaxation time from the excited states, compatible with the system of flow conservation equations, are derived. The relaxation time from the excited states indicates the weak dependency of the initial vibrational temperature. The empirical curve-fit formula for the improved e-V relaxation time is obtained.

Bolt clampup relaxation in a graphite/epoxy laminate

NASA Technical Reports Server (NTRS)

Shivakumar, K. N.; Crews, J. H., Jr.

1982-01-01

A simple bolted joint was analyzed to calculate bolt clampup relaxation for a graphite/epoxy (T300/5208) laminate. A viscoelastic finite element analysis of a double-lap joint with a steel bolt was conducted. Clampup forces were calculated for various steady-state temperature-moisture conditions using a 20-year exposure duration. The finite element analysis predicted that clampup forces relax even for the room-temperature-dry condition. The relaxations were 8, 13, 20, and 30 percent for exposure durations of 1 day, 1 month, 1 year, and 20 years, respectively. As expected, higher temperatures and moisture levels each increased the relaxation rate. The combined viscoelastic effects of steady-state temperature and moisture appeared to be additive. From the finite-element analysis, a simple equation was developed for clampup force relaxation. This generalized equation was used to calculate clampup forces for the same temperature-moisture conditions as used in the finite-element analysis. The two sets of calculated results agreed well.

Aging of Johari-Goldstein Relaxation in Structural Glasses

NASA Astrophysics Data System (ADS)

Yardimci, Hasan; Leheny, Robert L.

2006-03-01

Using frequency-dependent dielectric susceptibility measurements we characterize the aging in two supercooled liquids, sorbitol and xylitol, below their calorimetric glass transition temperatures, Tg. In addition to the alpha relaxation that tracks the structural dynamics, the susceptibilities of both liquids possess a secondary Johari-Goldstein relaxation at higher frequencies. Following a quench below Tg, the susceptibility slowly approaches equilibrium behavior. For both liquids, features of the Johari-Goldstein relaxation display a dependence on the time since the quench, or aging time, that is very similar to the age dependence of the alpha peak. However, one can not assign a single fictive temperature to both the alpha and Johari-Goldstein relaxations. For example, the peak frequency of the Johari-Goldstein relaxation remains constant during aging for sorbitol while it increases with age for xylitol, inconsistent with a decreasing fictive temperature. This behavior contrasts with that of the high frequency tail of the alpha peak whose shape and position track the aging of the main part of the peak.

Slow relaxation of cascade-induced defects in Fe

DOE PAGES

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.; ...

2015-02-17

On-the-fly kinetic Monte Carlo (KMC) simulations are performed to investigate slow relaxation of non-equilibrium systems. Point defects induced by 25 keV cascades in α -Fe are shown to lead to a characteristic time-evolution, described by the replenish and relax mechanism. Then, we produce an atomistically-based assessment of models proposed to explain the slow structural relaxation by focusing on the aggregation of 50 vacancies and 25 self-interstital atoms (SIA) in 10-lattice-parameter α-Fe boxes, two processes that are closely related to cascade annealing and exhibit similar time signature. Four atomistic effects explain the timescales involved in the evolution: defect concentration heterogeneities, concentration-enhancedmore » mobility, cluster-size dependent bond energies and defect-induced pressure. In conclusion, these findings suggest that the two main classes of models to explain slow structural relaxation, the Eyring model and the Gibbs model, both play a role to limit the rate of relaxation of these simple point-defect systems.« less

Relaxation Techniques for Handicapped Children: A Review of Literature.

ERIC Educational Resources Information Center

Zipkin, Dvora

1985-01-01

The paper discusses four major relaxation training approaches used with handicapped children: progressive muscle relaxation, biofeedback, yoga, and mental relaxation, which includes guided fantasy, imagery, and meditation. Descriptions of these techniques, the effects of their use with various populations, and reviews of recent studies of their…

Relaxation Training: Its Usefulness in the Middle School Curriculum.

ERIC Educational Resources Information Center

Matthews, Doris B.

A study examined multiple outcomes of relaxation training simultaneously in seventh grade classrooms. "Project Relaxation" measured cognitive (achievement) and affective (discipline, attendance, tardiness, and self-concept) changes with a program of relaxation training for 532 seventh grade students in 10 private and public middle schools in South…

Le Chatelier's principle with multiple relaxation channels

NASA Astrophysics Data System (ADS)

Gilmore, R.; Levine, R. D.

1986-05-01

Le Chatelier's principle is discussed within the constrained variational approach to thermodynamics. The formulation is general enough to encompass systems not in thermal (or chemical) equilibrium. Particular attention is given to systems with multiple constraints which can be relaxed. The moderation of the initial perturbation increases as additional constraints are removed. This result is studied in particular when the (coupled) relaxation channels have widely different time scales. A series of inequalities is derived which describes the successive moderation as each successive relaxation channel opens up. These inequalities are interpreted within the metric-geometry representation of thermodynamics.

Slow relaxation in weakly open rational polygons.

PubMed

Kokshenev, Valery B; Vicentini, Eduardo

2003-07-01

The interplay between the regular (piecewise-linear) and irregular (vertex-angle) boundary effects in nonintegrable rational polygonal billiards (of m equal sides) is discussed. Decay dynamics in polygons (of perimeter P(m) and small opening Delta) is analyzed through the late-time survival probability S(m) approximately equal t(-delta). Two distinct slow relaxation channels are established. The primary universal channel exhibits relaxation of regular sliding orbits, with delta=1. The secondary channel is given by delta>1 and becomes open when m>P(m)/Delta. It originates from vertex order-disorder dual effects and is due to relaxation of chaoticlike excitations.

Hydrophobicity and Charge Shape Cellular Metabolite Concentrations

PubMed Central

Bar-Even, Arren; Noor, Elad; Flamholz, Avi; Buescher, Joerg M.; Milo, Ron

2011-01-01

What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108) of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ∼100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts. PMID:21998563

Communication: Relaxation-limited electronic currents in extended reservoir simulations

NASA Astrophysics Data System (ADS)

Gruss, Daniel; Smolyanitsky, Alex; Zwolak, Michael

2017-10-01

Open-system approaches are gaining traction in the simulation of charge transport in nanoscale and molecular electronic devices. In particular, "extended reservoir" simulations, where explicit reservoir degrees of freedom are present, allow for the computation of both real-time and steady-state properties but require relaxation of the extended reservoirs. The strength of this relaxation, γ, influences the conductance, giving rise to a "turnover" behavior analogous to Kramers turnover in chemical reaction rates. We derive explicit, general expressions for the weak and strong relaxation limits. For weak relaxation, the conductance increases linearly with γ and every electronic state of the total explicit system contributes to the electronic current according to its "reduced" weight in the two extended reservoir regions. Essentially, this represents two conductors in series—one at each interface with the implicit reservoirs that provide the relaxation. For strong relaxation, a "dual" expression-one with the same functional form-results, except now proportional to 1/γ and dependent on the system of interest's electronic states, reflecting that the strong relaxation is localizing electrons in the extended reservoirs. Higher order behavior (e.g., γ2 or 1/γ2) can occur when there is a gap in the frequency spectrum. Moreover, inhomogeneity in the frequency spacing can give rise to a pseudo-plateau regime. These findings yield a physically motivated approach to diagnosing numerical simulations and understanding the influence of relaxation, and we examine their occurrence in both simple models and a realistic, fluctuating graphene nanoribbon.

Broadband spectral analysis of non-Debye dielectric relaxation in percolating heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuncer, Enis; Bellatar, J; Achour, M E

2011-01-01

In this study, the main features of dielectric relaxation in carbon black epoxy composites are discussed using several types of complementary modelling (i.e., the Cole-Cole phenomenological equation, Jonscher s universal dielectric response, and an approach that relies on a continuous distribution of relaxation times). These methods of characterizing the relaxation were conducted below Tg. Through the numerical model we can obtain the characteristic effective relaxation time and exponents straightforwardly. However, the true relaxation spectrum can be obtained from the distribution of relaxation times calculated from the complex dielectric permittivity. Over the compositional range explored, relaxation occurs by a Vogel-Tammam-Fulcher-like temperaturemore » dependence within the limits of experimental accuracy.« less

Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

PubMed Central

Frisvad, Jens C.; Kocev, Dragi; Džeroski, Sašo; Gunde-Cimerman, Nina

2016-01-01

The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A and UCA 1064-B). In particular an increase in NaCl concentration from 5% to 15% in the growth media increased the production of the toxic metabolites wallimidione, walleminol and walleminone. PMID:28036382

Substrate stress relaxation regulates cell spreading

NASA Astrophysics Data System (ADS)

Chaudhuri, Ovijit; Gu, Luo; Darnell, Max; Klumpers, Darinka; Bencherif, Sidi A.; Weaver, James C.; Huebsch, Nathaniel; Mooney, David J.

2015-02-01

Studies of cellular mechanotransduction have converged upon the idea that cells sense extracellular matrix (ECM) elasticity by gauging resistance to the traction forces they exert on the ECM. However, these studies typically utilize purely elastic materials as substrates, whereas physiological ECMs are viscoelastic, and exhibit stress relaxation, so that cellular traction forces exerted by cells remodel the ECM. Here we investigate the influence of ECM stress relaxation on cell behaviour through computational modelling and cellular experiments. Surprisingly, both our computational model and experiments find that spreading for cells cultured on soft substrates that exhibit stress relaxation is greater than cells spreading on elastic substrates of the same modulus, but similar to that of cells spreading on stiffer elastic substrates. These findings challenge the current view of how cells sense and respond to the ECM.

High resolution NMR study of T{sub 1} magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L., E-mail: ivanov@tomo.nsc.ru

2014-10-21

Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I–III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T{sub 1}-relaxation timesmore » at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.« less

A quantum relaxation-time approximation for finite fermion systems

NASA Astrophysics Data System (ADS)

Reinhard, P.-G.; Suraud, E.

2015-03-01

We propose a relaxation time approximation for the description of the dynamics of strongly excited fermion systems. Our approach is based on time-dependent density functional theory at the level of the local density approximation. This mean-field picture is augmented by collisional correlations handled in relaxation time approximation which is inspired from the corresponding semi-classical picture. The method involves the estimate of microscopic relaxation rates/times which is presently taken from the well established semi-classical experience. The relaxation time approximation implies evaluation of the instantaneous equilibrium state towards which the dynamical state is progressively driven at the pace of the microscopic relaxation time. As test case, we consider Na clusters of various sizes excited either by a swift ion projectile or by a short and intense laser pulse, driven in various dynamical regimes ranging from linear to strongly non-linear reactions. We observe a strong effect of dissipation on sensitive observables such as net ionization and angular distributions of emitted electrons. The effect is especially large for moderate excitations where typical relaxation/dissipation time scales efficiently compete with ionization for dissipating the available excitation energy. Technical details on the actual procedure to implement a working recipe of such a quantum relaxation approximation are given in appendices for completeness.

State resolved vibrational relaxation modeling for strongly nonequilibrium flows

NASA Astrophysics Data System (ADS)

Boyd, Iain D.; Josyula, Eswar

2011-05-01

Vibrational relaxation is an important physical process in hypersonic flows. Activation of the vibrational mode affects the fundamental thermodynamic properties and finite rate relaxation can reduce the degree of dissociation of a gas. Low fidelity models of vibrational activation employ a relaxation time to capture the process at a macroscopic level. High fidelity, state-resolved models have been developed for use in continuum gas dynamics simulations based on computational fluid dynamics (CFD). By comparison, such models are not as common for use with the direct simulation Monte Carlo (DSMC) method. In this study, a high fidelity, state-resolved vibrational relaxation model is developed for the DSMC technique. The model is based on the forced harmonic oscillator approach in which multi-quantum transitions may become dominant at high temperature. Results obtained for integrated rate coefficients from the DSMC model are consistent with the corresponding CFD model. Comparison of relaxation results obtained with the high-fidelity DSMC model shows significantly less excitation of upper vibrational levels in comparison to the standard, lower fidelity DSMC vibrational relaxation model. Application of the new DSMC model to a Mach 7 normal shock wave in carbon monoxide provides better agreement with experimental measurements than the standard DSMC relaxation model.

Rice Protein Matrix Enhances Circulating Levels of Xanthohumol Following Acute Oral Intake of Spent Hops in Humans.

PubMed

O'Connor, Annalouise; Konda, Veera; Reed, Ralph L; Christensen, J Mark; Stevens, Jan F; Contractor, Nikhat

2018-03-01

Xanthohumol (XN), a prenylated flavonoid found in hops, exhibits anti-inflammatory and antioxidant properties. However, poor bioavailability may limit therapeutic applications. As food components are known to modulate polyphenol absorption, the objective is to determine whether a protein matrix could enhance the bioavailability of XN post oral consumption in humans. This is a randomized, double-blind, crossover study in healthy participants (n = 6) evaluating XN and its major metabolites (isoxanthohumol [IX], 6- and 8-prenylnaringenin [6-PN, 8-PN]) for 6 h following consumption of 12.4 mg of XN delivered via a spent hops-rice protein matrix preparation or a control spent hops preparation. Plasma XN and metabolites are measured by LC-MS/MS. C max , T max , and area-under-the-curve (AUC) values were determined. Circulating XN and metabolite response to each treatment was not bioequivalent. Plasma concentrations of XN and XN + metabolites (AUC) are greater with consumption of the spent hops-rice protein matrix preparation. Compared to a standard spent hops powder, a protein-rich spent hops matrix demonstrates enhanced plasma levels of XN and metabolites following acute oral intake. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determinants of relaxation rate in rabbit skinned skeletal muscle fibres

PubMed Central

Luo, Ye; Davis, Jonathan P; Smillie, Lawrence B; Rall, Jack A

2002-01-01

The influence of Ca2+-activated force, the rate of dissociation of Ca2+ from troponin C (TnC) and decreased crossbridge detachment rate on the time course of relaxation induced by flash photolysis of diazo-2 in rabbit skinned psoas fibres was investigated at 15 °C. The rate of relaxation increased as the diazo-2 chelating capacity (i.e. free [diazo-2]/free [Ca2+]) increased. At a constant diazo-2 chelating capacity, the rate of relaxation was independent of the pre-photolysis Ca2+-activated force in the range 0.3-0.8 of maximum isometric force. A TnC mutant that exhibited increased Ca2+ sensitivity caused by a decreased Ca2+ dissociation rate in solution (M82Q TnC) also increased the Ca2+ sensitivity of steady-state force and decreased the rate of relaxation in fibres by approximately twofold. In contrast, a TnC mutant with decreased Ca2+ sensitivity caused by an increased Ca2+ dissociation rate in solution (NHdel TnC) decreased the Ca2+ sensitivity of steady-state force but did not accelerate relaxation. Decreasing the rate of crossbridge kinetics by reducing intracellular inorganic phosphate concentration ([Pi]) slowed relaxation by approximately twofold and led to two phases of relaxation, a slow linear phase followed by a fast exponential phase. In fibres, M82Q TnC further slowed relaxation in low [Pi] conditions by approximately twofold, whereas NHdel TnC had no significant effect on relaxation. These results are consistent with the interpretation that the Ca2+-dissociation rate and crossbridge detachment rate are similar in fast-twitch skeletal muscle, such that decreasing either rate slows relaxation, but accelerating Ca2+ dissociation has little effect on relaxation. PMID:12482894

Dynamics of human serum albumin studied by acoustic relaxation spectroscopy.

PubMed

Hushcha, T; Kaatze, U; Peytcheva, A

Sonic absorption spectra of solutions of human serum albumin (SA) in water and in aqueous phosphate buffer systems have been measured between 0.2 and 2000 MHz at different temperatures (15-35 degrees C), pH values (1.8-12.3), and protein concentrations (1-40 g/L). Several spectra, indicating relaxation processes in the whole frequency range, have been found. The spectra at neutral pH could be fitted well with an analytical function consisting of the asymptotic high frequency absorption and two relaxation contributions, a Debye-type relaxation term with discrete relaxation time and a term with asymmetric continuous distribution of relaxation times. Both relaxation contributions were observed in water and in buffer solutions and increased with protein concentration. The contribution represented by a Debye-type term is practically independent of temperature and was attributed to cooperative conformational changes of the polypeptide chain featuring a relaxation time of about 400 ns. The distribution of the relaxation times corresponding to the second relaxation contribution was characterized by a short time cutoff, between about 0.02 and 0.4 ns depending on temperature, and a long time tail extending to microseconds. Such relaxation behavior was interpreted in terms of solute-solvent interactions reflecting various hydration layers of HSA molecules. At acid and alkaline pH, an additional Debye-type contribution with relaxation time in the range of 30-100 ns exists. It seems to be due to proton transfer reactions of protein side-chain groups. The kinetic and thermodynamic parameters of these processes have been estimated from these first measurements to indicate the potential of acoustic spectra for the investigation of the elementary kinetics of albumin processes. Copyright 2004 Wiley Periodicals, Inc. Biopolymers, 2004

Viscous relaxation of Ganymede's impact craters: Constraints on heat flux

USGS Publications Warehouse

Bland, Michael T.; Singer, Kelsi N.; McKinnon, William B.; Schenk, Paul M.

2017-01-01

Measurement of crater depths in Ganymede’s dark terrain have revealed substantial numbers of unusually shallow craters indicative of viscous relaxation [see companion paper: Singer, K.N., Schenk, P. M., Bland, M.T., McKinnon, W.B., (2017). Relaxed impact craters on Ganymede: Regional variations and high heat flow. Icarus, submitted]. These viscously relaxed craters provide insight into the thermal history of the dark terrain: the rate of relaxation depends on the size of the crater and the thermal structure of the lithosphere. Here we use finite element simulations of crater relaxation to constrain the heat flux within the dark terrain when relaxation occurred. We show that the degree of viscous relaxation observed cannot be achieved through radiogenic heating alone, even if all of the relaxed craters are ancient and experienced the high radiogenic fluxes present early in the satellite’s history. For craters with diameter ≥ 10 km, heat fluxes of 40–50 mW m-2−2"> can reproduce the observed crater depths, but only if the fluxes are sustained for ∼1 Gyr. These craters can also be explained by shorter-lived “heat pulses” with magnitudes of ∼100 mW m-2−2"> and timescales of 10–100 Myr. At small crater diameters (4 km) the observed shallow depths are difficult to achieve even when heat fluxes as high as 150 mW m-2−2"> are sustained for 1 Gyr. The extreme thermal conditions required to viscously relax small craters may indicate that mechanisms other than viscous relaxation, such as topographic degradation, are also in play at small crater diameters. The timing of the relaxation event(s) is poorly constrained due to the sparsity of adequate topographic information, though it likely occurred in Ganymede’s middle history (neither recently, nor shortly after satellite formation). The consistency between the timing and magnitude of the heat fluxes derived here and those inferred from other tectonic features suggests that a single event

Viscous relaxation of Ganymede's impact craters: Constraints on heat flux

NASA Astrophysics Data System (ADS)

Bland, Michael T.; Singer, Kelsi N.; McKinnon, William B.; Schenk, Paul M.

2017-11-01

Measurement of crater depths in Ganymede's dark terrain have revealed substantial numbers of unusually shallow craters indicative of viscous relaxation [see companion paper: Singer, K.N., Schenk, P. M., Bland, M.T., McKinnon, W.B., (2017). Relaxed impact craters on Ganymede: Regional variations and high heat flow. Icarus, submitted]. These viscously relaxed craters provide insight into the thermal history of the dark terrain: the rate of relaxation depends on the size of the crater and the thermal structure of the lithosphere. Here we use finite element simulations of crater relaxation to constrain the heat flux within the dark terrain when relaxation occurred. We show that the degree of viscous relaxation observed cannot be achieved through radiogenic heating alone, even if all of the relaxed craters are ancient and experienced the high radiogenic fluxes present early in the satellite's history. For craters with diameter ≥ 10 km, heat fluxes of 40-50 mW m-2 can reproduce the observed crater depths, but only if the fluxes are sustained for ∼1 Gyr. These craters can also be explained by shorter-lived "heat pulses" with magnitudes of ∼100 mW m-2 and timescales of 10-100 Myr. At small crater diameters (4 km) the observed shallow depths are difficult to achieve even when heat fluxes as high as 150 mW m-2 are sustained for 1 Gyr. The extreme thermal conditions required to viscously relax small craters may indicate that mechanisms other than viscous relaxation, such as topographic degradation, are also in play at small crater diameters. The timing of the relaxation event(s) is poorly constrained due to the sparsity of adequate topographic information, though it likely occurred in Ganymede's middle history (neither recently, nor shortly after satellite formation). The consistency between the timing and magnitude of the heat fluxes derived here and those inferred from other tectonic features suggests that a single event caused both Ganymede's tectonic deformation and

Multilayer Relaxation and Surface Energies of Metallic Surfaces

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Rodriguez, Agustin M.; Ferrante, John

1994-01-01

The perpendicular and parallel multilayer relaxations of fcc (210) surfaces are studied using equivalent crystal theory (ECT). A comparison with experimental and theoretical results is made for AI(210). The effect of uncertainties in the input parameters on the magnitudes and ordering of surface relaxations for this semiempirical method is estimated. A new measure of surface roughness is proposed. Predictions for the multilayer relaxations and surface energies of the (210) face of Cu and Ni are also included.

Vibrational Relaxation and Dynamical Transitions in Atactic Polystyrene

NASA Astrophysics Data System (ADS)

Zhao, Hanqing; Park, Yung; Painter, Paul

2009-03-01

Infrared bands and Raman lines recorded in the frequency domain have a counterpart in the time domain in the form of time-correlation functions, which are sensitive to molecular dynamics on the picosecond time scale. This is explored by calculating time correlation functions and their variation with temperature for the conformationally insensitive modes observed near 1601 cm-1 and 1583 cm-1 in the infrared spectrum of atactic polystyrene. The correlation functions were modeled by assuming that there is a fast relaxation process characterized by a single relaxation time that is inhomogeneously broadened by a slower process, also characterized by a single relaxation time. The fundamental mode, near 1583 cm-1, is inhomogeneously broadened, but the relaxation time calculated for this mode is sensitive to temperature as a result of anharmonic coupling to a combination mode. A change in the modulation of the 1583 cm-1 band becomes apparent about 10--20 degrees below the thermally measured Tg. Relaxation times at first increase then decrease and becomes negligible at temperatures near 180 degrees. These results are consistent with theories of the glass transition.

Biologically Active Secondary Metabolites from the Fungi.

PubMed

Bills, Gerald F; Gloer, James B

2016-11-01

Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly limitless potential for metabolic variation and an untapped resource for drug discovery and synthetic biology. Much of the ecological success of the filamentous fungi in colonizing the planet is owed to their ability to deploy their secondary metabolites in concert with their penetrative and absorptive mode of life. Fungal secondary metabolites exhibit biological activities that have been developed into life-saving medicines and agrochemicals. Toxic metabolites, known as mycotoxins, contaminate human and livestock food and indoor environments. Secondary metabolites are determinants of fungal diseases of humans, animals, and plants. Secondary metabolites exhibit a staggering variation in chemical structures and biological activities, yet their biosynthetic pathways share a number of key characteristics. The genes encoding cooperative steps of a biosynthetic pathway tend to be located contiguously on the chromosome in coregulated gene clusters. Advances in genome sequencing, computational tools, and analytical chemistry are enabling the rapid connection of gene clusters with their metabolic products. At least three fungal drug precursors, penicillin K and V, mycophenolic acid, and pleuromutilin, have been produced by synthetic reconstruction and expression of respective gene clusters in heterologous hosts. This review summarizes general aspects of fungal secondary metabolism and recent developments in our understanding of how and why fungi make secondary metabolites, how these molecules are produced, and how their biosynthetic genes are distributed across the Fungi. The breadth of fungal secondary metabolite diversity is highlighted by recent information on the biosynthesis of important fungus-derived metabolites that have contributed to human health and agriculture and that have negatively impacted crops

NMR spin-rotation relaxation and diffusion of methane

NASA Astrophysics Data System (ADS)

Singer, P. M.; Asthagiri, D.; Chapman, W. G.; Hirasaki, G. J.

2018-05-01

The translational diffusion-coefficient and the spin-rotation contribution to the 1H NMR relaxation rate for methane (CH4) are investigated using MD (molecular dynamics) simulations, over a wide range of densities and temperatures, spanning the liquid, supercritical, and gas phases. The simulated diffusion-coefficients agree well with measurements, without any adjustable parameters in the interpretation of the simulations. A minimization technique is developed to compute the angular velocity for non-rigid spherical molecules, which is used to simulate the autocorrelation function for spin-rotation interactions. With increasing diffusivity, the autocorrelation function shows increasing deviations from the single-exponential decay predicted by the Langevin theory for rigid spheres, and the deviations are quantified using inverse Laplace transforms. The 1H spin-rotation relaxation rate derived from the autocorrelation function using the "kinetic model" agrees well with measurements in the supercritical/gas phase, while the relaxation rate derived using the "diffusion model" agrees well with measurements in the liquid phase. 1H spin-rotation relaxation is shown to dominate over the MD-simulated 1H-1H dipole-dipole relaxation at high diffusivity, while the opposite is found at low diffusivity. At high diffusivity, the simulated spin-rotation correlation time agrees with the kinetic collision time for gases, which is used to derive a new expression for 1H spin-rotation relaxation, without any adjustable parameters.

Synoptic forcing of wind relaxations at Pt. Conception, California

NASA Astrophysics Data System (ADS)

Fewings, Melanie R.; Washburn, Libe; Dorman, Clive E.; Gotschalk, Christopher; Lombardo, Kelly

2016-08-01

Over the California Current upwelling system in summer, the prevailing upwelling-favorable winds episodically weaken (relax) or reverse direction for a few days. Near Pt. Conception, California, the wind usually does not reverse, but wind relaxation allows poleward oceanic coastal flow with ecological consequences. To determine the offshore extent and synoptic forcing of these wind relaxations, we formed composite averages of wind stress from the QuikSCAT satellite and atmospheric pressure from the North American Regional Reanalysis (NARR) using 67 wind relaxations during summer 2000-2009. Wind relaxations at Pt. Conception are the third stage of an event sequence that repeatedly affects the west coast of North America in summer. First, 5-7 days before the wind weakens near Pt. Conception, the wind weakens or reverses off Oregon and northern California. Second, the upwelling-favorable wind intensifies along central California. Third, the wind relaxes at Pt. Conception, and the area of weakened winds extends poleward to northern California over 3-5 days. The NARR underestimates the wind stress within ˜200 km of coastal capes by a factor of 2. Wind relaxations at Pt. Conception are caused by offshore extension of the desert heat low. This synoptic forcing is related to event cycles that cause wind reversal as in Halliwell and Allen (1987) and Mass and Bond (1996), but includes weaker events. The wind relaxations extend ˜600 km offshore, similarly to the California-scale hydraulic expansion fan shaping the prevailing winds, and ˜1000 km alongshore, limited by an opposing pressure gradient force at Cape Mendocino.

Relaxation dispersion in MRI induced by fictitious magnetic fields.

PubMed

Liimatainen, Timo; Mangia, Silvia; Ling, Wen; Ellermann, Jutta; Sorce, Dennis J; Garwood, Michael; Michaeli, Shalom

2011-04-01

A new method entitled Relaxation Along a Fictitious Field (RAFF) was recently introduced for investigating relaxations in rotating frames of rank ≥ 2. RAFF generates a fictitious field (E) by applying frequency-swept pulses with sine and cosine amplitude and frequency modulation operating in a sub-adiabatic regime. In the present work, MRI contrast is created by varying the orientation of E, i.e. the angle ε between E and the z″ axis of the second rotating frame. When ε > 45°, the amplitude of the fictitious field E generated during RAFF is significantly larger than the RF field amplitude used for transmitting the sine/cosine pulses. Relaxation during RAFF was investigated using an invariant-trajectory approach and the Bloch-McConnell formalism. Dipole-dipole interactions between identical (like) spins and anisochronous exchange (e.g., exchange between spins with different chemical shifts) in the fast exchange regime were considered. Experimental verifications were performed in vivo in human and mouse brain. Theoretical and experimental results demonstrated that changes in ε induced a dispersion of the relaxation rate constants. The fastest relaxation was achieved at ε ≈ 56°, where the averaged contributions from transverse components during the pulse are maximal and the contribution from longitudinal components are minimal. RAFF relaxation dispersion was compared with the relaxation dispersion achieved with off-resonance spin lock T(₁ρ) experiments. As compared with the off-resonance spin lock T(₁ρ) method, a slower rotating frame relaxation rate was observed with RAFF, which under certain experimental conditions is desirable. Copyright © 2011 Elsevier Inc. All rights reserved.

Drug repositioning for enzyme modulator based on human metabolite-likeness.

PubMed

Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

2017-05-31

Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for

Unravelling the mechanisms of vibrational relaxation in solution.

PubMed

Grubb, Michael P; Coulter, Philip M; Marroux, Hugo J B; Orr-Ewing, Andrew J; Ashfold, Michael N R

2017-04-01

We present a systematic study of the mode-specific vibrational relaxation of NO 2 in six weakly-interacting solvents (perfluorohexane, perfluoromethylcyclohexane, perfluorodecalin, carbon tetrachloride, chloroform, and d-chloroform), chosen to elucidate the dominant energy transfer mechanisms in the solution phase. Broadband transient vibrational absorption spectroscopy has allowed us to extract quantum state-resolved relaxation dynamics of the two distinct NO 2 fragments produced from the 340 nm photolysis of N 2 O 4 → NO 2 (X) + NO 2 (A) and their separate paths to thermal equilibrium. Distinct relaxation pathways are observed for the NO 2 bending and stretching modes, even at energies as high as 7000 cm -1 above the potential minimum. Vibrational energy transfer is governed by different interaction mechanisms in the various solvent environments, and proceeds with timescales ranging from 20-1100 ps. NO 2 relaxation rates in the perfluorocarbon solvents are identical despite differences in acceptor mode state densities, infrared absorption cross sections, and local solvent structure. Vibrational energy is shown to be transferred to non-vibrational solvent degrees of freedom (V-T) through impulsive collisions with the perfluorocarbon molecules. Conversely, NO 2 relaxation in chlorinated solvents is reliant on vibrational resonances (V-V) while V-T energy transfer is inefficient and thermal excitation of the surrounding solvent molecules inhibits faster vibrational relaxation through direct complexation. Intramolecular vibrational redistribution allows the symmetric stretch of NO 2 to act as a gateway for antisymmetric stretch energy to exit the molecule. This study establishes an unprecedented level of detail for the cooling dynamics of a solvated small molecule, and provides a benchmark system for future theoretical studies of vibrational relaxation processes in solution.

The WEIZMASS spectral library for high-confidence metabolite identification

NASA Astrophysics Data System (ADS)

Shahaf, Nir; Rogachev, Ilana; Heinig, Uwe; Meir, Sagit; Malitsky, Sergey; Battat, Maor; Wyner, Hilary; Zheng, Shuning; Wehrens, Ron; Aharoni, Asaph

2016-08-01

Annotation of metabolites is an essential, yet problematic, aspect of mass spectrometry (MS)-based metabolomics assays. The current repertoire of definitive annotations of metabolite spectra in public MS databases is limited and suffers from lack of chemical and taxonomic diversity. Furthermore, the heterogeneity of the data prevents the development of universally applicable metabolite annotation tools. Here we present a combined experimental and computational platform to advance this key issue in metabolomics. WEIZMASS is a unique reference metabolite spectral library developed from high-resolution MS data acquired from a structurally diverse set of 3,540 plant metabolites. We also present MatchWeiz, a multi-module strategy using a probabilistic approach to match library and experimental data. This strategy allows efficient and high-confidence identification of dozens of metabolites in model and exotic plants, including metabolites not previously reported in plants or found in few plant species to date.

Excited-state relaxation in PbSe quantum dots

NASA Astrophysics Data System (ADS)

An, Joonhee M.; Califano, Marco; Franceschetti, Alberto; Zunger, Alex

2008-04-01

In solids the phonon-assisted, nonradiative decay from high-energy electronic excited states to low-energy electronic excited states is picosecond fast. It was hoped that electron and hole relaxation could be slowed down in quantum dots, due to the unavailability of phonons energy matched to the large energy-level spacings ("phonon-bottleneck"). However, excited-state relaxation was observed to be rather fast (⩽1ps) in InP, CdSe, and ZnO dots, and explained by an efficient Auger mechanism, whereby the excess energy of electrons is nonradiatively transferred to holes, which can then rapidly decay by phonon emission, by virtue of the densely spaced valence-band levels. The recent emergence of PbSe as a novel quantum-dot material has rekindled the hope for a slow down of excited-state relaxation because hole relaxation was deemed to be ineffective on account of the widely spaced hole levels. The assumption of sparse hole energy levels in PbSe was based on an effective-mass argument based on the light effective mass of the hole. Surprisingly, fast intraband relaxation times of 1-7ps were observed in PbSe quantum dots and have been considered contradictory with the Auger cooling mechanism because of the assumed sparsity of the hole energy levels. Our pseudopotential calculations, however, do not support the scenario of sparse hole levels in PbSe: Because of the existence of three valence-band maxima in the bulk PbSe band structure, hole energy levels are densely spaced, in contradiction with simple effective-mass models. The remaining question is whether the Auger decay channel is sufficiently fast to account for the fast intraband relaxation. Using the atomistic pseudopotential wave functions of Pb2046Se2117 and Pb260Se249 quantum dots, we explicitly calculated the electron-hole Coulomb integrals and the P →S electron Auger relaxation rate. We find that the Auger mechanism can explain the experimentally observed P →S intraband decay time scale without the need to

Relaxation phenomena in AOT-water-decane critical and dense microemulsions

NASA Astrophysics Data System (ADS)

Letamendia, L.; Pru-Lestret, E.; Panizza, P.; Rouch, J.; Sciortino, F.; Tartaglia, P.; Hashimoto, C.; Ushiki, H.; Risso, D.

2001-11-01

We report on extensive measurements of the low and high frequencies sound velocity and sound absorption in AOT-water-decane microemulsions deduced from ultrasonic and, for the first time as far as the absorption is concerned, from Brillouin scattering experiments. New experimental results on dielectric relaxation are also reported. Our results, which include data taken for critical as well as dense microemulsions, show new interesting relaxation phenomena. The relaxation frequencies deduced from very high frequency acoustical measurements are in good agreement with new high frequency dielectric relaxation measurements. We show that along the critical isochore, sound dispersion, relaxation frequency, and static dielectric permittivity can be accurately fitted to power laws. The absolute values of the new exponents we derived from experimental data are nearly equal, and they are very close to β=0.33 characterising the shape of the coexistence curve. The exponent characterising the infinite frequency permittivity is very close to 0.04 relevant to the diverging shear viscosity. For dense microemulsions, two well defined relaxation domains have been identified and the temperature variations of the sound absorption and the zero frequency dielectric permittivity bear striking similarities. We also show that the relaxation frequency of the slow relaxation process is almost independent of temperature and volume fraction and so cannot be attributed to percolation phenomena, whereas it can more likely be attributed to an intrinsic relaxation process probably connected to membrane fluctuations.

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

PubMed Central

Karoum, F.

1987-01-01

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on

Testosterone metabolism revisited: discovery of new metabolites.

PubMed

Pozo, Oscar J; Marcos, Josep; Ventura, Rosa; Fabregat, Andreu; Segura, Jordi

2010-10-01

The metabolism of testosterone is revisited. Four previously unreported metabolites were detected in urine after hydrolysis with KOH using a liquid chromatography-tandem mass spectrometry method and precursor ion scan mode. The metabolites were characterized by a product ion scan obtained with accurate mass measurements. Androsta-4,6-dien-3,17-dione, androsta-1,4-dien-3,17-dione, 17-hydroxy-androsta-4,6-dien-3-one and 15-androsten-3,17-dione were proposed as feasible structures for these metabolites on the basis of the mass spectrometry data. The proposed structures were confirmed by analysis of synthetic reference compounds. Only 15-androsten-3,17-dione could not be confirmed, owing to the lack of a commercially available standard. That all four compounds are testosterone metabolites was confirmed by the qualitative analysis of several urine samples collected before and after administration of testosterone undecanoate. The metabolite androsta-1,4-dien-3,17-dione has a structure analogous to that of the exogenous anabolic steroid boldenone. Specific transitions for boldenone and its metabolite 17β-hydroxy-5β-androst-1-en-3-one were also monitored. Both compounds were also detected after KOH treatment, suggesting that this metabolic pathway is involved in the endogenous detection of boldenone previously reported by several authors.

Dynamics in supercooled polyalcohols: Primary and secondary relaxation

NASA Astrophysics Data System (ADS)

Döß, A.; Paluch, M.; Sillescu, H.; Hinze, G.

2002-10-01

We have studied details of the molecular dynamics in a series of pure polyalcohols by means of dielectric spectroscopy and 2H nuclear magnetic resonance (NMR). From glycerol to threitol, xylitol and sorbitol a systematic change in the dynamics of the primary and secondary relaxation is found. With increasing molecular weight and fragility an increase in the width of the α-peak is observed. Details of the molecular reorientation process responsible for the α-relaxation were exploited by two-dimensional NMR experiments. It is found that in the same sequence of polyalcohols the appearance of the secondary relaxation changes gradually from a wing type scenario to a pronounced β-peak. From NMR experiments using selectively deuterated samples the molecular origin of the secondary relaxation could be elucidated in more detail.

Non-targeted metabolite profiling of citrus juices as a tool for variety discrimination and metabolite flow analysis.

PubMed

Arbona, Vicent; Iglesias, Domingo J; Gómez-Cadenas, Aurelio

2015-02-05

Genetic diversity of citrus includes intrageneric hybrids, cultivars arising from cross-pollination and/or somatic mutations with particular biochemical compounds such as sugar, acids and secondary metabolite composition. Secondary metabolite profiles of juices from 12 commercial varieties grouped into blonde and navel types, mandarins, lemons and grapefruits were analyzed by LC/ESI-QTOF-MS. HCA on metabolite profiling data revealed the existence of natural groups demarcating fruit types and varieties associated to specific composition patterns. The unbiased classification provided by HCA was used for PLS-DA to find the potential variables (mass chromatographic features) responsible for the classification. Abscisic acid and derivatives, several flavonoids and limonoids were identified by analysis of mass spectra. To facilitate interpretation, metabolites were represented as flow charts depicting biosynthetic pathways. Mandarins 'Fortune' and 'Hernandina' along with oranges showed higher ABA contents and ABA degradation products were present as glycosylated forms in oranges and certain mandarins. All orange and grapefruit varieties showed high limonin contents and its glycosylated form, that was only absent in lemons. The rest of identified limonoids were highly abundant in oranges. Particularly, Sucrenya cultivar showed a specific accumulation of obacunone and limonoate A-ring lactone. Polymethoxylated flavanones (tangeritin and isomers) were absolutely absent from lemons and grapefruits whereas kaempferol deoxyhexose hexose isomer #2, naringin and neohesperidin were only present in these cultivars. Analysis of relative metabolite build-up in closely-related genotypes allowed the efficient demarcation of cultivars and suggested the existence of genotype-specific regulatory mechanisms underlying the differential metabolite accumulation.

Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

PubMed

Okayasu, Hiroaki; Shinozaki, Takahiro; Osone, Akira; Ozeki, Yuji; Shimoda, Kazutaka

2014-03-29

Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

Dependence of Brownian and Néel relaxation times on magnetic field strength

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deissler, Robert J., E-mail: rjd42@case.edu; Wu, Yong; Martens, Michael A.

2014-01-15

Purpose: In magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS) the relaxation time of the magnetization in response to externally applied magnetic fields is determined by the Brownian and Néel relaxation mechanisms. Here the authors investigate the dependence of the relaxation times on the magnetic field strength and the implications for MPI and MPS. Methods: The Fokker–Planck equation with Brownian relaxation and the Fokker–Planck equation with Néel relaxation are solved numerically for a time-varying externally applied magnetic field, including a step-function, a sinusoidally varying, and a linearly ramped magnetic field. For magnetic fields that are applied as a stepmore » function, an eigenvalue approach is used to directly calculate both the Brownian and Néel relaxation times for a range of magnetic field strengths. For Néel relaxation, the eigenvalue calculations are compared to Brown's high-barrier approximation formula. Results: The relaxation times due to the Brownian or Néel mechanisms depend on the magnitude of the applied magnetic field. In particular, the Néel relaxation time is sensitive to the magnetic field strength, and varies by many orders of magnitude for nanoparticle properties and magnetic field strengths relevant for MPI and MPS. Therefore, the well-known zero-field relaxation times underestimate the actual relaxation times and, in particular, can underestimate the Néel relaxation time by many orders of magnitude. When only Néel relaxation is present—if the particles are embedded in a solid for instance—the authors found that there can be a strong magnetization response to a sinusoidal driving field, even if the period is much less than the zero-field relaxation time. For a ferrofluid in which both Brownian and Néel relaxation are present, only one relaxation mechanism may dominate depending on the magnetic field strength, the driving frequency (or ramp time), and the phase of the magnetization

[Relaxation techniques for chronic pain].

PubMed

Diezemann, A

2011-08-01

Relaxation techniques are an integral part of the psychological therapy of chronic pain and follow very different objectives. These techniques lead to muscular and vegetative stabilization, serve as distraction from pain, to build up the internal focus of control and thus to improve self-efficacy. Additional targets are improvement of body awareness and stress management, shielding from sensory stimuli and recurrence prevention of migraine as well a sleeping aid. The most commonly used and best studied method is progressive muscle relaxation which has a good compliance because it is easy to learn and has a high plausibility for patients.

Methionine Metabolites in Patients With Sepsis.

PubMed

Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

2018-01-01

Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes

Effects of aripiprazole and the Taq1A polymorphism in the dopamine D2 receptor gene on the clinical response and plasma monoamine metabolites level during the acute phase of schizophrenia.

PubMed

Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Mori, Azuma; Kanno, Keiko; Yang, Qiaohui; Mashiko, Hirobumi; Numata, Yoshihiko; Niwa, Shin-Ichi

2012-02-01

The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene could be related to the response to antipsychotics. We examined the effects of the Taq1A polymorphism on the plasma monoamine metabolites during the treatment of schizophrenia with aripiprazole, a DRD2 partial agonist. Thirty Japanese patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol (pMHPG) before and after treatment. The Taq1A polymorphism was genotyped with polymerase chain reaction. Aripiprazole improved the acute symptoms of schizophrenia and decreased pHVA in responders (P = 0.023) but not in nonresponders (P = 0.28). Although A1 allele carriers showed a tendency to respond to aripiprazole (61.5%) compared to A1 allele noncarriers (29.4%) (P = 0.078), there was not statistically significant difference in the response between the 2 genotype groups. There were significant effect for response (P = 0.013) and genotype × response interaction (P = 0.043) on the change of pHVA. The changes of pHVA differ between responders and nonresponders in A1 allele carriers but not in A1 allele noncarriers. There were no genotype or response effects or genotype × response interaction on the changes of the plasma levels of 3-methoxy-4hydroxyphenylglycol. Our preliminary results suggest that Taq1A polymorphism may be partly associated with changes in pHVA during acute schizophrenia.

Evaluation of the stereoselective biotransformation of permethrin in human liver microsomes: contributions of cytochrome P450 monooxygenases to the formation of estrogenic metabolites.

PubMed

Lavado, Ramon; Li, Jiwen; Rimoldi, John M; Schlenk, Daniel

2014-04-21

Permethrin (PM) is a pyrethroid insecticide that exists as 4 enantiomers. Biotransformation of PM to estrogen receptor agonists (3-phenoxybenzyl alcohol (PBOH) and 3-(4'-hydroxyphenoxy)-benzyl alcohol (3,4 PBOH)) has been shown to be stereoselective in other vertebrate species. This study evaluated the biotransformation of PM enantiomers in human liver microsomes and with recombinant CYP3A4 and CYP2C19. PBOH and 3,4 PBOH were the only metabolites detected from in vitro incubations including each of the 4 enantiomers of PM with 1R-trans PM having the most efficient NADPH-catalyzed biotransformation to both metabolites. Coincubation with the CYP inhibitor ketoconazole and time course experiments with liver microsomes and recombinant CYP2C19 and CYP3A4 indicated CYP-catalyzed stereoselective cleavage of the ester followed by 4-hydoxylation to 3,4' PBOH. These data indicate potential dispositional differences may occur with PM enantiomers and a shift in putative molecular targets. While cleavage of pyrethroid esters lead to detoxification of the acute neurological effects, formation of the benzyl alcohol and hydroxylated metabolite may lead to estrogenic responses, since each of these metabolites are estrogen receptor ligands. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting.

PubMed

Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó; Kuttner, Eva; Ásgeirsdóttir, Margrét E; Young, Louise C; Green, David H; Edrada-Ebel, Ruangelie; Duncan, Katherine R

2016-01-08

The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149-2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations.

Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting

PubMed Central

Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó.; Kuttner, Eva; Ásgeirsdóttir, Margrét E.; Young, Louise C.; Green, David H.; Edrada-Ebel, Ruangelie; Duncan, Katherine R.

2016-01-01

The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149–2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations. PMID:26761036

Mutagenicity of 1-nitropyrene metabolites from lung S9.

PubMed

King, L C; Kohan, M J; Ball, L M; Lewtas, J

1984-04-01

The mutagenicity of 1-nitropyrene metabolites from rabbit lung S9 incubates was evaluated using the Salmonella typhimurium plate incorporation assay with strain TA98, with and without Aroclor-induced rat liver S9. The following metabolites were isolated, identified and quantitated by HPLC: 1-nitropyrene -4,5- or -9,10-dihydrodiol (K-DHD), N-acetyl-1-aminopyrene ( NAAP ), 1-aminopyrene (1-AMP), 10-hydroxy-1-nitropyrene, 4-, 5-, 6-, 8- or 9-monohydroxy-1-nitropyrene (phenols) and 3-hydroxy-1-nitropyrene. The predominant metabolites formed by lung S9 incubates were K-DHD, 3-OH-1-nitropyrene and phenols. All of the metabolites were mutagenic in the absence of the exogenous rat liver S9 metabolic activation system, and several, including two unidentified metabolites were more potent than the parent 1-nitropyrene. The mutagenicity of 3 of the metabolites ( NAAP , 10-OH-1-nitropyrene and phenols) were enhanced by S9 while most of the other metabolites were less mutagenic in the presence of S9. These results indicate that lung tissue is capable of both oxidative and reductive metabolism which produced mutagenic metabolites, several of which were more potent than the parent compound, 1-NP.

Electron and hole relaxation pathways in semiconductor quantum dots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klimov, V.I.; McBranch, D.W.; Leatherdale, C.A.

1999-11-01

Femtosecond (fs) broad-band transient absorption (TA) is used to study the intraband relaxation and depopulation dynamics of electron and hole quantized states in CdSe nanocrystals (NC{close_quote}s) with a range of surface properties. Instead of the drastic reduction in the energy relaxation rate expected due to a {open_quotes}phonon bottleneck,{close_quotes} we observe a fast subpicosecond 1P-to-1S electron relaxation, with the rate exceeding that due to phonon emission in bulk semiconductors. The energy relaxation is enhanced with reducing the NC{close_quote}s radius, and does not show any dependence on the NC surface properties (quality of the surface passivation). These data indicate that electron energymore » relaxation occurs by neither multiphonon emission nor by coupling to surface defects, but is likely meditated by Auger-type electron-hole energy transfer. We use fs infrared TA to probe electron and hole intraband transitions, which allows us to distinguish between electron and hole relaxation pathways leading to the depopulation of NC quantized states. In contrast to the electron relaxation, which is controlled by NC surface passivation, the depopulation of hole quantized states is extremely fast (sub-ps-to-ps time scales) in all types of samples, independent of NC surface treatment (including NC{close_quote}s overcoated with a ZnS layer). Our results indicate that ultrafast hole dynamics are not due to trapping at localized surface defects such as a vacancy, but rather arise from relaxation into intrinsic NC states or intrinsically unpassivated interface states. {copyright} {ital 1999} {ital The American Physical Society}« less

Recreational alcohol use induces changes in the concentrations of choline-containing compounds and total creatine in the brain: a (1)H MRS study of healthy subjects.

PubMed

Tunc-Skarka, Nuran; Weber-Fahr, Wolfgang; Ende, Gabriele

2015-10-01

It has previously been reported that even social alcohol consumption affects the magnetic resonance spectroscopy (MRS) signals of choline-containing compounds (tCho). The purpose of this study was to investigate whether the consumption of alcohol affects the concentrations of the metabolites tCho, N-acetylaspartate, creatine, or myo-inositol and/or their T 2 relaxation times. (1)H MR spectra were obtained at 3 T from a frontal white matter voxel of 25 healthy subjects with social alcohol consumption (between 0 and 25.9 g/day). Absolute brain metabolite concentrations and T 2 relaxation times of metabolites were examined via MRS measurements at different echo times. Metabolite concentrations and their T 2 relaxation times were correlated with subjects' alcohol consumption, controlling for age. We observed positive correlations of absolute tCho and phosphocreatine and creatine (tCr) concentrations with alcohol consumption but no correlation between any metabolite T 2 relaxation time and alcohol consumption. This study shows that even social alcohol consumption affects the concentrations of tCho and tCr in cerebral white matter. Future studies assessing brain tCho and tCr levels should control for the confounding factor alcohol consumption.

Immersed boundary lattice Boltzmann model based on multiple relaxation times

NASA Astrophysics Data System (ADS)

Lu, Jianhua; Han, Haifeng; Shi, Baochang; Guo, Zhaoli

2012-01-01

As an alterative version of the lattice Boltzmann models, the multiple relaxation time (MRT) lattice Boltzmann model introduces much less numerical boundary slip than the single relaxation time (SRT) lattice Boltzmann model if some special relationship between the relaxation time parameters is chosen. On the other hand, most current versions of the immersed boundary lattice Boltzmann method, which was first introduced by Feng and improved by many other authors, suffer from numerical boundary slip as has been investigated by Le and Zhang. To reduce such a numerical boundary slip, an immerse boundary lattice Boltzmann model based on multiple relaxation times is proposed in this paper. A special formula is given between two relaxation time parameters in the model. A rigorous analysis and the numerical experiments carried out show that the numerical boundary slip reduces dramatically by using the present model compared to the single-relaxation-time-based model.

Intuitive approach to the unified theory of spin relaxation

NASA Astrophysics Data System (ADS)

Szolnoki, Lénárd; Dóra, Balázs; Kiss, Annamária; Fabian, Jaroslav; Simon, Ferenc

2017-12-01

Spin relaxation is conventionally discussed using two different approaches for materials with and without inversion symmetry. The former is known as the Elliott-Yafet (EY) theory and for the latter the D'yakonov-Perel' (DP) theory applies. We discuss herein a simple and intuitive approach to demonstrate that the two seemingly disparate mechanisms are closely related. A compelling analogy between the respective Hamiltonians is presented, and that the usual derivation of spin-relaxation times, in the respective frameworks of the two theories, can be performed. The result also allows us to obtain less canonical spin-relaxation regimes, i.e. the generalization of the EY when the material has a large quasiparticle broadening, and the DP mechanism in ultrapure semiconductors. The method also allows a practical and intuitive numerical implementation of the spin-relaxation calculation, which is demonstrated for MgB2, which has anomalous spin-relaxation properties.

[Relaxant effects of protopine on smooth muscles].

PubMed

Huang, Y H; Zhang, Z Z; Jiang, J X

1991-01-01

The relaxant effects of protopine (Pro) on smooth muscles were studied by recording isotonic contraction and radioimmunoassay. Pro relaxed the contraction of rabbit thoracic aorta, mesenteric artery, portal vein and guinea pig ileum and taenia colon induced by high K+ (70 mmol.L-1). Pro also inhibited the contraction of rabbit thoracic aorta, mesenteric artery, portal vein induced by NE (0.3 mumol.L-1) and guinea pig taenia colon induced by BaCl2 (1 mmol.L-1). Pro inhibited the intracellular Ca2+ release, but did not inhibit Ca2+ influx induced by NE. These results suggested that the smooth muscle relaxant mechanism of action of Pro may be the inhibition of intracellular Ca2+ release.

Relaxation techniques for stress

MedlinePlus

... of your body. These sensors measure your skin temperature, brain waves, breathing, and muscle activity. You can ... more about any of these techniques through local classes, books, videos, or online. Alternative Names Relaxation response ...

Relaxation Techniques.

DTIC Science & Technology

1985-04-01

Colonel Robert Fowler for sponsoring this project, Major Richard Hartson for diligently editing each draft and the men of ACSC Seminar A-li ( Mix 1...and AWC Seminar 15 ( Mix 1) for encouraging the author to introduce relaxation techniques to other military officers through this videotape. Special...anytime and without having to stop what you’re doing. The individuals were usually surprised at how easily deep breathing initiated a feeling of

Relaxation of Isolated Ventricular Cardiomyocytes by a Voltage-Dependent Process

NASA Astrophysics Data System (ADS)

Bridge, John H. B.; Spitzer, Kenneth W.; Ershler, Philip R.

1988-08-01

Cell contraction and relaxation were measured in single voltage-clamped guinea pig cardiomyocytes to investigate the contribution of sarcolemmal Na+-Ca2+ exchange to mechanical relaxation. Cells clamped from -80 to 0 millivolts displayed initial phasic and subsequent tonic contractions; caffeine reduced or abolished the phasic and enlarged the tonic contraction. The rate of relaxation from tonic contractions was steeply voltage-dependent and was significantly slowed in the absence of a sarcolemmal Na+ gradient. Tonic contractions elicited in the absence of a Na+ gradient promptly relaxed when external Na+ was applied, reflecting activation of Na+-Ca2+ exchange. It appears that a voltage-dependent Na+-Ca2+ exchange can rapidly mechanically relax mammalian heart muscle.

Coupling of 2,4,6-trinitrotoluene (TNT) metabolites onto humic monomers by a new laccase from Trametes modesta.

PubMed

Nyanhongo, Gibson S; Couto, Susana Rodríguez; Guebitz, Georg M

2006-06-01

During degradation of trinitrotoluene (TNT) by Trametes modesta, addition of humic monomers prevented the accumulation of all major stable TNT metabolites (aminodinitrotoluenes [AMDNT]) by at least 92% in the presence of 200 mM ferulic acid and guaiacol. Acute toxicity tests with individual TNT metabolites and in T. modesta cultures supplemented with 200 microM TNT demonstrated that the TNT biodegradation process lead to less toxic metabolites. Toxicity decreased in the order TNT>4-HADNT (4-hydroxylaminodinitrotoluene)>2-HADNT>2,6-DNT (2,6-dinitrotoluene)>2',2',6,6-azoxytetranitrotoluene>4-AMDNT>2-AMDNT>2,4-diamninonitrotoluene (2,4-DAMNT) while 2,4-DNT and 2,6-DAMNT were the least toxic. Ferulic acid is the best candidate for immobilization TNT biodegradation metabolites since it prevented the accumulation of AMDNTs in cultures during TNT biodegradation and its products were less toxic. All humic monomers were very effective in immobilizing 2-HADNT [100%], 4-HADNT [100%] and 2,2,6,6-azoxytetranitrotoluene [100%]. Two distinct laccase isoenzymes (LTM1 and LTM2) potentially involved in immobilization of TNT degradation products were purified to electrophoretic homogeneity. LTM1 and LTM2 have molecular weights of 77.6 and 52.5 kDa, are 18% and 24% glycosylated, have pI values of 3.6 and 4.2, respectively. Both enzymes oxidized all the typical laccase substrates tested. LTM1 showed highest kinetic constants (K(m)=0.03 microM; K(cat)=8.8 4x 10(7)s(-1)) with syringaldazine as substrate.

MHD simulation of relaxation transition to a flipped relaxed state in spherical torus

NASA Astrophysics Data System (ADS)

Kanki, Takashi; Nagata, Masayoshi; Kagei, Yasuhiro

2008-11-01

Recently, it has been demonstrated in the HIST device that in spite of the violation of the Kruskal-Shafranov stability condition, a normal spherical torus (ST) plasma has relaxed to a flipped ST state through a transient reversed-field pinch-like state when the vacuum toroidal field is decreased and its direction is reversed [1]. It has been also observed during this relaxation transition process that not only the toroidal field but also the poloidal field reverses polarity spontaneously and that the ion flow velocity is strongly fluctuated and abruptly increased up to > 50 km/s. The purpose of the present study is to investigate the plasma flows and the relevant MHD relaxation phenomena to elucidate this transition mechanism by using three-dimensional MHD simulations [2]. It is found from the numerical results that the magnetic reconnection between the open and closed field lines occurs due to the non-linear growth of the n=1 kink instability of the central open flux, generating the toroidal flow ˜ 60 km/s in the direction of the toroidal current. The n=1 kink instability and the plasma flows driven by the magnetic reconnection are consider to be responsible for the self-reversal of the magnetic fields. [1] M. Nagata el al., Phys. Rev. Lett. 90, 225001 (2003). [2] Y. Kagei el al., Plasma. Phys. Control. Fusion 45, L17 (2003).

STUDIES OF METABOLITE-PROTEIN INTERACTIONS: A REVIEW

PubMed Central

Matsuda, Ryan; Bi, Cong; Anguizola, Jeanethe; Sobansky, Matthew; Rodriquez, Elliot; Badilla, John Vargas; Zheng, Xiwei; Hage, Benjamin; Hage, David S.

2014-01-01

The study of metabolomics can provide valuable information about biochemical pathways and processes at the molecular level. There have been many reports that have examined the structure, identity and concentrations of metabolites in biological systems. However, the binding of metabolites with proteins is also of growing interest. This review examines past reports that have looked at the binding of various types of metabolites with proteins. An overview of the techniques that have been used to characterize and study metabolite-protein binding is first provided. This is followed by examples of studies that have investigated the binding of hormones, fatty acids, drugs or other xenobiotics, and their metabolites with transport proteins and receptors. These examples include reports that have considered the structure of the resulting solute-protein complexes, the nature of the binding sites, the strength of these interactions, the variations in these interactions with solute structure, and the kinetics of these reactions. The possible effects of metabolic diseases on these processes, including the impact of alterations in the structure and function of proteins, are also considered. PMID:24321277

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

PubMed Central

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. l-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase. PMID:26273653

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta.

PubMed

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. L-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase.

Nuclear spin relaxation of methane in solid xenon

NASA Astrophysics Data System (ADS)

Sugimoto, Takeru; Arakawa, Ichiro; Yamakawa, Koichiro

2018-03-01

Nuclear spin relaxation of methane in solid xenon has been studied by infrared spectroscopy. From the analysis of the temporal changes of the rovibrational peaks, the rates of the nuclear spin relaxation of I = 2 ← 1 correlated to the rotational relaxation of J = 0 ← 1 were obtained at temperatures of 5.1-11.5 K. On the basis of the temperature dependence of the relaxation rate, the activation energy of the indirect two-phonon process was determined to be 50 ± 6 K, which is in good agreement with the rotational transition energies of J = 2 ← 1 and J = 3 ← 1. Taking into account this result and the spin degeneracy, we argue that the lowest J = 3 level in which the I = 1 and I = 2 states are degenerate acts as the intermediate point of the indirect process.

Hepatic Metabolomics Investigation in Acute and Chronic Murine Toxoplasmosis.

PubMed

Chen, Xiao-Qing; Elsheikha, Hany M; Hu, Rui-Si; Hu, Gui-Xue; Guo, Shu-Ling; Zhou, Chun-Xue; Zhu, Xing-Quan

2018-01-01

Toxoplasma gondii poses a great threat to human health, with no approved vaccine available for the treatment of T. gondii infection. T. gondii infections are not limited to the brain, and may also affect other organs especially the liver. Identification of host liver molecules or pathways involved in T. gondii replication process may lead to the discovery of novel anti- T. gondii targets. Here, we analyzed the metabolic profile of the liver of mice on 11 and 30 days postinfection (dpi) with type II T. gondii Pru strain. Global metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 389 significant metabolites from acutely infected mice; and 368 from chronically infected mice, when compared with control mice. Multivariate statistical analysis revealed distinct metabolic signatures from acutely infected, chronically infected and control mice. Infection influenced several metabolic processes, in particular those for lipids and amino acids. Metabolic pathways, such as steroid hormone biosynthesis, primary bile acid biosynthesis, bile secretion, and biosynthesis of unsaturated fatty acids were perturbed during the whole infection process, particularly during the acute stage of infection. The present results provide insight into hepatic metabolic changes that occur in BALB/c mice during acute and chronic T. gondii infection.

Novel Approach to Classify Plants Based on Metabolite-Content Similarity.

PubMed

Liu, Kang; Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki; Altaf-Ul-Amin, Md; Kanaya, Shigehiko

2017-01-01

Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations.

Novel Approach to Classify Plants Based on Metabolite-Content Similarity

PubMed Central

Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki

2017-01-01

Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations. PMID:28164123

Effects of intra-aortic balloon pump counterpulsation on left ventricular mechanoenergetics in a porcine model of acute ischemic heart failure.

PubMed

Malliaras, Konstantinos; Charitos, Efstratios; Diakos, Nikolaos; Pozios, Iraklis; Papalois, Apostolos; Terrovitis, John; Nanas, John

2014-12-01

We investigated the effects of intra-aortic balloon pump (IABP) counterpulsation on left ventricular (LV) contractility, relaxation, and energy consumption and probed the underlying physiologic mechanisms in 12 farm pigs, using an ischemia-reperfusion model of acute heart failure. During both ischemia and reperfusion, IABP support unloaded the LV, decreased LV energy consumption (pressure-volume area, stroke work), and concurrently improved LV mechanical performance (ejection fraction, stroke volume, cardiac output). During reperfusion exclusively, IABP also improved LV relaxation (tau) and contractility (Emax, PRSW). The beneficial effects of IABP support on LV relaxation and contractility correlated with IABP-induced augmentation of coronary blood flow. In conclusion, we find that during both ischemia and reperfusion, IABP support optimizes LV energetic performance (decreases energy consumption and concurrently improves mechanical performance) by LV unloading. During reperfusion exclusively, IABP support also improves LV contractility and active relaxation, possibly due to a synergistic effect of unloading and augmentation of coronary blood flow.

[Relaxation to defuse acting out for dangerous schizophrenics].

PubMed

Bogar, Mireille; Bouchard, Jean-Pierre

2015-01-01

Relaxation is often considered as a contraindication in the management of schizophrenics. An experiment carried out with dangerous schizophrenics at the unit for dangerous patients at Cadillac general hospital revealed that, on the contrary, such an opinion is not necessarily valid in all cases. Indeed, for many of these patients, relaxation can have positive effects on their clinical state. As with its other indications, relaxation must be practised by clinicians who have an in-depth knowledge of techniques to use and of mental disorders treated in that way.

Stochastic tools hidden behind the empirical dielectric relaxation laws

NASA Astrophysics Data System (ADS)

Stanislavsky, Aleksander; Weron, Karina

2017-03-01

The paper is devoted to recent advances in stochastic modeling of anomalous kinetic processes observed in dielectric materials which are prominent examples of disordered (complex) systems. Theoretical studies of dynamical properties of ‘structures with variations’ (Goldenfield and Kadanoff 1999 Science 284 87-9) require application of such mathematical tools—by means of which their random nature can be analyzed and, independently of the details distinguishing various systems (dipolar materials, glasses, semiconductors, liquid crystals, polymers, etc), the empirical universal kinetic patterns can be derived. We begin with a brief survey of the historical background of the dielectric relaxation study. After a short outline of the theoretical ideas providing the random tools applicable to modeling of relaxation phenomena, we present probabilistic implications for the study of the relaxation-rate distribution models. In the framework of the probability distribution of relaxation rates we consider description of complex systems, in which relaxing entities form random clusters interacting with each other and single entities. Then we focus on stochastic mechanisms of the relaxation phenomenon. We discuss the diffusion approach and its usefulness for understanding of anomalous dynamics of relaxing systems. We also discuss extensions of the diffusive approach to systems under tempered random processes. Useful relationships among different stochastic approaches to the anomalous dynamics of complex systems allow us to get a fresh look at this subject. The paper closes with a final discussion on achievements of stochastic tools describing the anomalous time evolution of complex systems.

A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

PubMed

Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

2018-06-01

Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Is Relaxation Training Effective in the Treatment of Clinical Depression?

ERIC Educational Resources Information Center

Beaty, Lee A.

The process of relaxation is a complex triarchic phenomenon that incorporates behavioral, cognitive, and physiological components. Existing literature is surveyed in order to determine the efficacy of treating various forms of depression with cognitive-behavioral relaxation strategies. Relaxation training has been shown to be effective in treating…

Dynamical relaxation in 2HDM models

NASA Astrophysics Data System (ADS)

Lalak, Zygmunt; Markiewicz, Adam

2018-03-01

Dynamical relaxation provides an interesting solution to the hierarchy problem in face of the missing signatures of any new physics in recent experiments. Through a dynamical process taking place in the inflationary phase of the Universe it manages to achieve a small electroweak scale without introducing new states observable in current experiments. Appropriate approximation makes it possible to derive an explicit formula for the final vevs in the double-scanning scenario extended to a model with two Higgs doublets (2HDM). Analysis of the relaxation in the 2HDM confirms that in a general case it is impossible to keep vevs of both scalars small, unless fine-tuning is present or additional symmetries are cast upon the Lagrangian. Within the slightly constrained variant of the 2HDM, where odd powers of the fields’ expectation values are not present (which can be easily enforced by requiring that the doublets have different gauge transformations or by imposing a global symmetry) it is shown that the difference between the vevs of two scalars tends to be proportional to the cutoff. The analysis of the relaxation in 2HDM indicates that in a general case the relaxation would be stopped by the first doublet that gains a vev, with the other one remaining vevless with a mass of the order of the cutoff. This happens to conform with the inert doublet model.

Arresting relaxation in Pickering Emulsions

NASA Astrophysics Data System (ADS)

Atherton, Tim; Burke, Chris

2015-03-01

Pickering emulsions consist of droplets of one fluid dispersed in a host fluid and stabilized by colloidal particles absorbed at the fluid-fluid interface. Everyday materials such as crude oil and food products like salad dressing are examples of these materials. Particles can stabilize non spherical droplet shapes in these emulsions through the following sequence: first, an isolated droplet is deformed, e.g. by an electric field, increasing the surface area above the equilibrium value; additional particles are then adsorbed to the interface reducing the surface tension. The droplet is then allowed to relax toward a sphere. If more particles were adsorbed than can be accommodated by the surface area of the spherical ground state, relaxation of the droplet is arrested at some non-spherical shape. Because the energetic cost of removing adsorbed colloids exceeds the interfacial driving force, these configurations can remain stable over long timescales. In this presentation, we present a computational study of the ordering present in anisotropic droplets produced through the mechanism of arrested relaxation and discuss the interplay between the geometry of the droplet, the dynamical process that produced it, and the structure of the defects observed.

Resistivity scaling and electron relaxation times in metallic nanowires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moors, Kristof, E-mail: kristof@itf.fys.kuleuven.be; Imec, Kapeldreef 75, B-3001 Leuven; Sorée, Bart

2014-08-14

We study the resistivity scaling in nanometer-sized metallic wires due to surface roughness and grain-boundaries, currently the main cause of electron scattering in nanoscaled interconnects. The resistivity has been obtained with the Boltzmann transport equation, adopting the relaxation time approximation of the distribution function and the effective mass approximation for the conducting electrons. The relaxation times are calculated exactly, using Fermi's golden rule, resulting in a correct relaxation time for every sub-band state contributing to the transport. In general, the relaxation time strongly depends on the sub-band state, something that remained unclear with the methods of previous work. The resistivitymore » scaling is obtained for different roughness and grain-boundary properties, showing large differences in scaling behavior and relaxation times. Our model clearly indicates that the resistivity is dominated by grain-boundary scattering, easily surpassing the surface roughness contribution by a factor of 10.« less

Thermally induced magnetic relaxation in square artificial spin ice.

PubMed

Andersson, M S; Pappas, S D; Stopfel, H; Östman, E; Stein, A; Nordblad, P; Mathieu, R; Hjörvarsson, B; Kapaklis, V

2016-11-24

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice - we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

Thermally induced magnetic relaxation in square artificial spin ice

NASA Astrophysics Data System (ADS)

Andersson, M. S.; Pappas, S. D.; Stopfel, H.; Östman, E.; Stein, A.; Nordblad, P.; Mathieu, R.; Hjörvarsson, B.; Kapaklis, V.

2016-11-01

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice - we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

Mechanism of resveratrol-induced relaxation in the human gallbladder.

PubMed

Tsai, Ching-Chung; Lee, Ming-Che; Tey, Shu-Leei; Liu, Ching-Wen; Huang, Shih-Che

2017-05-08

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips. We studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker). The present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways. This study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of

Spin-locking vs. chemical exchange saturation transfer MRI for investigating chemical exchange process between water and labile metabolite protons

PubMed Central

Jin, Tao; Autio, Joonas; Obata, Takayuki; Kim, Seong-Gi

2010-01-01

Chemical exchange saturation transfer (CEST) and spin-locking (SL) experiments were both able to probe the exchange process between protons of non-equivalent chemical environments. To compare the characteristics of the CEST and SL approaches in the study of chemical exchange effects, we performed CEST and SL experiments at varied pH and concentrated metabolites with exchangeable amide, amine, and hydroxyl protons at 9.4 T. Our results show that: i) On-resonance SL is most sensitive to chemical exchanges in the intermediate exchange regime and is able to detect hydroxyl and amine protons on a millimolar concentration scale. Off-resonance SL and CEST approaches are sensitive to slow-exchanging protons when an optimal SL or saturation pulse power matches the exchanging rate, respectively. ii) Offset frequency-dependent SL and CEST spectra are very similar, and can be explained well with an SL model recently developed by Trott and Palmer. iii) The exchange rate and population of metabolite protons can be determined from offset-dependent SL or CEST spectra or from on-resonance SL relaxation dispersion measurements. iv) The asymmetry of the magnetization transfer ratio (MTRasym) is highly dependent on the choice of saturation pulse power. In the intermediate exchange regime, MTRasym becomes complicated and should be interpreted with care. PMID:21500270

Urinary pesticide metabolites in school students from northern Thailand.

PubMed

Panuwet, Parinya; Prapamontol, Tippawan; Chantara, Somporn; Barr, Dana B

2009-05-01

We evaluated exposure to pesticides among secondary school students aged 12-13 years old in Chiang Mai Province, Thailand. Pesticide-specific urinary metabolites were used as biomarkers of exposure for a variety of pesticides, including organophosphorus insecticides, synthetic pyrethroid insecticides and selected herbicides. We employed a simple solid-phase extraction with analysis using isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). A total of 207 urine samples from Thai students were analyzed for 18 specific pesticide metabolites. We found 14 metabolites in the urine samples tested; seven of them were detected with a frequency > or=17%. The most frequently detected metabolites were 2-[(dimethoxyphosphorothioyl) sulfanyl] succinic acid (malathion dicarboxylic acid), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TPCY; metabolite of chlorpyrifos), 2,4-dichlorophenoxyacetic acid (2,4-D), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (c-DCCA and t-DCCA; metabolite of permethrin) and 3-phenoxybenzoic acid (3-PBA; metabolite of pyrethroids). The students were classified into 4 groups according to their parental occupations: farmers (N=60), merchants and traders (N=39), government and company employees (N=52), and laborers (N=56). Children of farmers had significantly higher urinary concentrations of pyrethroid insecticide metabolites than did other children (p<0.05). Similarly, children of agricultural families had significantly higher pyrethroid metabolite concentrations. Males had significantly higher values of PNP (Mann-Whitney test, p=0.009); however, no other sex-related differences were observed. Because parental occupation and agricultural activities seemed to have little influence on pesticide levels, dietary sources were the likely contributors to the metabolite levels observed.

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

PubMed Central

Imig, John D.; Hye Khan, Md. Abdul

2018-01-01

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function. PMID:26756638

NMR relaxation studies in doped poly-3-methylthiophene

NASA Astrophysics Data System (ADS)

Singh, K. Jugeshwar; Clark, W. G.; Gaidos, G.; Reyes, A. P.; Kuhns, P.; Thompson, J. D.; Menon, R.; Ramesh, K. P.

2015-05-01

NMR relaxation rates (1 /T1 ), magnetic susceptibility, and electrical conductivity studies in doped poly-3-methylthiophene are reported in this paper. The magnetic susceptibility data show the contributions from both Pauli and Curie spins, with the size of the Pauli term depending strongly on the doping level. Proton and fluorine NMR relaxation rates have been studied as a function of temperature (3-300 K) and field (for protons at 0.9, 9.0, 16.4, and 23.4 T, and for fluorine at 9.0 T). The temperature dependence of T1 is classified into three regimes: (a) For T <(g μBB /2 kB ) , the relaxation mechanism follows a modified Korringa relation due to electron-electron interactions and disorder. 1H - T1 is due to the electron-nuclear dipolar interaction in addition to the contact term. (b) For the intermediate temperature range (g μBB /2 kB ) relaxation mechanism is via spin diffusion to the paramagnetic centers. (c) In the high-temperature regime and at low Larmor frequency the relaxation follows the modified Bloembergen, Purcell, and Pound model. T1 data analysis has been carried out in light of these models depending upon the temperature and frequency range of study. Fluorine relaxation data have been analyzed and attributed to the P F6 reorientation. The cross relaxation among the 1H and 19F nuclei has been observed in the entire temperature range suggesting the role of magnetic dipolar interaction modulated by the reorientation of the symmetric molecular subgroups. The data analysis shows that the enhancement in the Korringa ratio is greater in a less conducting sample. Intra- and interchain hopping of charge carriers is found to be a dominant relaxation mechanism at low temperature. Frequency dependence of T1-1 on temperature shows that at low temperature [T <(g μBB /2 kB ) ] the system shows three dimensions and changes to quasi one dimension at

Cole-Cole broadening in dielectric relaxation and strange kinetics.

PubMed

Puzenko, Alexander; Ishai, Paul Ben; Feldman, Yuri

2010-07-16

We present a fresh appraisal of the Cole-Cole (CC) description of dielectric relaxation. While the approach is phenomenological, it demonstrates a fundamental connection between the parameters of the CC dispersion. Based on the fractal nature of the time set representing the interaction of the relaxing dipole with its encompassing matrix, and the Kirkwood-Froehlich correlation factor, a new 3D phase space linking together the kinetic and structural properties is proposed. The evolution of the relaxation process is represented in this phase space by a trajectory, which is determined by the variation of external macroscopic parameters. As an example, the validity of the approach is demonstrated on two porous silica glasses exhibiting a CC relaxation process.

Vogel-Fulcher dependence of relaxation rates in a nematic monomer and elastomer

NASA Astrophysics Data System (ADS)

Shenoy, D.; Filippov, S.; Aliev, F.; Keller, P.; Thomsen, D.; Ratna, B.

2000-12-01

Dielectric relaxation spectroscopy is used to study the relaxation processes in a nematic monomer and the corresponding cross-linked polymer nematic liquid crystal (elastomer). In the frequency window 10 mHz to 2 GHz the monomer liquid crystal shows a single relaxation whereas the polymer exhibits three relaxation processes, two of which are quantitatively analyzed. The temperature dependence of relaxation times in both the monomer and polymer follows a Vogel-Fulcher behavior. The relaxation processes are identified with specific molecular motions and activation energies are calculated in a linear approximation for comparison with literature data.

Slowing hot-carrier relaxation in graphene using a magnetic field

NASA Astrophysics Data System (ADS)

Plochocka, P.; Kossacki, P.; Golnik, A.; Kazimierczuk, T.; Berger, C.; de Heer, W. A.; Potemski, M.

2009-12-01

A degenerate pump-probe technique is used to investigate the nonequilibrium carrier dynamics in multilayer graphene. Two distinctly different dynamics of the carrier relaxation are observed. A fast relaxation (˜50fs) of the carriers after the initial effect of phase-space filling followed by a slower relaxation (˜4ps) due to thermalization. Both relaxation processes are less efficient when a magnetic field is applied at low temperatures which is attributed to the suppression of the electron-electron Auger scattering due to the nonequidistant Landau-level spacing of the Dirac fermions in graphene.

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

PubMed Central

Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

2016-01-01

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID

Picosecond absorption relaxation measured with nanosecond laser photoacoustics

PubMed Central

Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin; Wang, Lihong V.

2010-01-01

Picosecond absorption relaxation—central to many disciplines—is typically measured by ultrafast (femtosecond or picosecond) pump-probe techniques, which however are restricted to optically thin and weakly scattering materials or require artificial sample preparation. Here, we developed a reflection-mode relaxation photoacoustic microscope based on a nanosecond laser and measured picosecond absorption relaxation times. The relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, were measured at 576 nm. The added advantages in dispersion susceptibility, laser-wavelength availability, reflection sensing, and expense foster the study of natural—including strongly scattering and nonfluorescent—materials. PMID:21079726

Alternate Forms Reliability of the Behavioral Relaxation Scale: Preliminary Results

ERIC Educational Resources Information Center

Lundervold, Duane A.; Dunlap, Angel L.

2006-01-01

Alternate forms reliability of the Behavioral Relaxation Scale (BRS; Poppen,1998), a direct observation measure of relaxed behavior, was examined. A single BRS score, based on long duration observation (5-minute), has been found to be a valid measure of relaxation and is correlated with self-report and some physiological measures. Recently,…

Wideband RELAX and wideband CLEAN for aeroacoustic imaging

NASA Astrophysics Data System (ADS)

Wang, Yanwei; Li, Jian; Stoica, Petre; Sheplak, Mark; Nishida, Toshikazu

2004-02-01

Microphone arrays can be used for acoustic source localization and characterization in wind tunnel testing. In this paper, the wideband RELAX (WB-RELAX) and the wideband CLEAN (WB-CLEAN) algorithms are presented for aeroacoustic imaging using an acoustic array. WB-RELAX is a parametric approach that can be used efficiently for point source imaging without the sidelobe problems suffered by the delay-and-sum beamforming approaches. WB-CLEAN does not have sidelobe problems either, but it behaves more like a nonparametric approach and can be used for both point source and distributed source imaging. Moreover, neither of the algorithms suffers from the severe performance degradations encountered by the adaptive beamforming methods when the number of snapshots is small and/or the sources are highly correlated or coherent with each other. A two-step optimization procedure is used to implement the WB-RELAX and WB-CLEAN algorithms efficiently. The performance of WB-RELAX and WB-CLEAN is demonstrated by applying them to measured data obtained at the NASA Langley Quiet Flow Facility using a small aperture directional array (SADA). Somewhat surprisingly, using these approaches, not only were the parameters of the dominant source accurately determined, but a highly correlated multipath of the dominant source was also discovered.

Holographic grating relaxation technique for soft matter science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesnichii, Vasilii, E-mail: vasilii.lesnichii@physchem.uni-freiburg.de; ITMO University, Kronverksky prospekt 49, Saint-Petersburg 197101; Kiessling, Andy

2016-06-17

The holographic grating relaxation technique also known as forced Rayleigh scattering consists basically in writing a holographic grating in the specimen of interest and monitoring its diffraction efficiency as a function of time, from which valuable information on mass or heat transfer and photoinduced transformations can be extracted. In a more detailed view, the shape of the relaxation curve and the relaxation rate as a function of the grating period were found to be affected by the architecture of diffusing species (molecular probes) that constitute the grating, as well as that of the environment they diffuse in, thus making itmore » possible to access and study spatial heterogeneity of materials and different modes of e.g., polymer motion. Minimum displacements and spatial domains approachable by the technique are in nanometer range, well below spatial periods of holographic gratings. In the present paper, several cases of holographic relaxation in heterogeneous media and complex motions are exemplified. Nano- to micro-structures or inhomogeneities comparable in spatial scale with holographic gratings manifest themselves in relaxation experiments via non-exponential decay (stepwise or stretched), spatial-period-dependent apparent diffusion coefficient, or unusual dependence of diffusion coefficient on molecular volume of diffusing probes.« less

Wideband RELAX and wideband CLEAN for aeroacoustic imaging.

PubMed

Wang, Yanwei; Li, Jian; Stoica, Petre; Sheplak, Mark; Nishida, Toshikazu

2004-02-01

Microphone arrays can be used for acoustic source localization and characterization in wind tunnel testing. In this paper, the wideband RELAX (WB-RELAX) and the wideband CLEAN (WB-CLEAN) algorithms are presented for aeroacoustic imaging using an acoustic array. WB-RELAX is a parametric approach that can be used efficiently for point source imaging without the sidelobe problems suffered by the delay-and-sum beamforming approaches. WB-CLEAN does not have sidelobe problems either, but it behaves more like a nonparametric approach and can be used for both point source and distributed source imaging. Moreover, neither of the algorithms suffers from the severe performance degradations encountered by the adaptive beamforming methods when the number of snapshots is small and/or the sources are highly correlated or coherent with each other. A two-step optimization procedure is used to implement the WB-RELAX and WB-CLEAN algorithms efficiently. The performance of WB-RELAX and WB-CLEAN is demonstrated by applying them to measured data obtained at the NASA Langley Quiet Flow Facility using a small aperture directional array (SADA). Somewhat surprisingly, using these approaches, not only were the parameters of the dominant source accurately determined, but a highly correlated multipath of the dominant source was also discovered.

Extended MHD modeling of tearing-driven magnetic relaxation

NASA Astrophysics Data System (ADS)

Sauppe, J. P.; Sovinec, C. R.

2017-05-01

Discrete relaxation events in reversed-field pinch relevant configurations are investigated numerically with nonlinear extended magnetohydrodynamic (MHD) modeling, including the Hall term in Ohm's law and first-order ion finite Larmor radius effects. Results show variability among relaxation events, where the Hall dynamo effect may help or impede the MHD dynamo effect in relaxing the parallel current density profile. The competitive behavior arises from multi-helicity conditions where the dominant magnetic fluctuation is relatively small. The resulting changes in parallel current density and parallel flow are aligned in the core, consistent with experimental observations. The analysis of simulation results also confirms that the force density from fluctuation-induced Reynolds stress arises subsequent to the drive from the fluctuation-induced Lorentz force density. Transport of the momentum density is found to be dominated by the fluctuation-induced Maxwell stress over most of the cross section with viscous and gyroviscous contributions being large in the edge region. The findings resolve a discrepancy with respect to the relative orientation of current density and flow relaxation, which had not been realized or investigated in King et al. [Phys. Plasmas 19, 055905 (2012)], where only the magnitude of flow relaxation is actually consistent with experimental results.

Emerging new strategies for successful metabolite identification in metabolomics

PubMed Central

Bingol, Kerem; Bruschweiler-Li, Lei; Li, Dawei; Zhang, Bo; Xie, Mouzhe; Brüschweiler, Rafael

2016-01-01

This review discusses strategies for the identification of metabolites in complex biological mixtures, as encountered in metabolomics, which have emerged in the recent past. These include NMR database-assisted approaches for the identification of commonly known metabolites as well as novel combinations of NMR and MS analysis methods for the identification of unknown metabolites. The use of certain chemical additives to the NMR tube can permit identification of metabolites with specific physical chemical properties. PMID:26915807

[Fenspiride in patients with acute bronchitis].

PubMed

Płusa, Tadeusz; Ochwat, Agnieszka

2005-07-01

Fenspiride is an anti-inflammatory drug that may have a role in inhibition of histamine receptor H1 and influence a production of archidonic acid metabolites. The efficacy and tolerance of fenspiride therapy have been performed in patients with acute bronchitis. 597 patients, 51% females and 49% males, aged 39+/-18 years, were observed because of acute bronchitis. Fenspiride (Eurespal, Servier) was given in a dose of 240 mg per day (80 mg three times daily) for 14 consecutive days. During two following medical examinations - after 7 and 14 days of treatment, clinical symptoms of disease, therapy efficacy and tolerance were determined. Mean duration of acute bronchitis before fenspiride therapy was 2.3+/-1.3 days. In most of the patients (72%) a moderate, and in 27% mild degree of disease was diagnosed. Only 1% of patients were diagnosed as severe. Total evaluation of fenspiride efficacy in examined patients with acute bronchitis showed complete relief of symptoms after 7 days of therapy in 24% and after 14 days in 87% of patients. In 6% of patients after 7 days and in 1% after 14 days of fenspiride therapy no improvement was obtained. 28 adverse reactions were determined in 26 patients (4.3%): vertigo in 7, nausea in 6, somnolence in 5, palpitations in 4, fatigue in 2, abdominal pain in 2 and other symptoms in 2 patients. In 8 patients the therapy was discontinued after 7 days because of adverse reactions. In performed observations in patients with acute bronchitis the high clinical efficacy of fenspiride therapy. In 12% of patients an antibiotic support was necessary to obtain relief of the symptoms. Very good tolerance of the 14 days therapy was determined and it is recommended for safe clinical application.

Generalized Elliott-Yafet spin-relaxation time for arbitrary spin mixing

NASA Astrophysics Data System (ADS)

Vollmar, Svenja; Hilton, David J.; Schneider, Hans Christian

2017-08-01

We extend our recent result for the spin-relaxation time due to acoustic electron-phonon scattering in degenerate bands with spin mixing [New J. Phys. 18, 023012 (2016), 10.1088/1367-2630/18/2/023012] to include interactions with optical phonons, and present a numerical evaluation of the spin-relaxation time for intraband hole-phonon scattering in the heavy-hole (HH) bands of bulk GaAs. Comparing our computed spin-relaxation times to the conventional Elliott-Yafet result quantitatively demonstrates that the latter underestimates the spin-relaxation time because it does not correctly describe how electron-phonon interactions change the (vector) spin expectation value of the single-particle states. We show that the conventional Elliott-Yafet spin relaxation time is a special case of our result for weak spin mixing.

Exchange-Induced Relaxation in the Presence of a Fictitious Field

PubMed Central

Sorce, Dennis J.; Mangia, Silvia; Liimatainen, Timo; Garwood, Michael; Michaeli, Shalom

2014-01-01

In the present study we derive a solution for two site fast exchange-induced relaxation in the presence of a fictitious magnetic field as generated by amplitude and frequency modulated RF pulses. This solution provides a means to analyze data obtained from relaxation experiments with the method called RAFFn (Relaxation Along a Fictitious Field of rank n), in which a fictitious field is created in a coordinate frame undergoing multi-fold rotation about n axes (rank n). The RAFF2 technique is relevant to MRI relaxation methods that provide good contrast enhancement for tumor detection. The relaxation equations for n = 2 are derived for the fast exchange regime using density matrix formalism. The method of derivation can be further extended to obtain solutions for n > 2. PMID:24911888

Regulation and Role of Fungal Secondary Metabolites.

PubMed

Macheleidt, Juliane; Mattern, Derek J; Fischer, Juliane; Netzker, Tina; Weber, Jakob; Schroeckh, Volker; Valiante, Vito; Brakhage, Axel A

2016-11-23

Fungi have the capability to produce a tremendous number of so-called secondary metabolites, which possess a multitude of functions, e.g., communication signals during coexistence with other microorganisms, virulence factors during pathogenic interactions with plants and animals, and in medical applications. Therefore, research on this topic has intensified significantly during the past 10 years and thus knowledge of regulatory mechanisms and the understanding of the role of secondary metabolites have drastically increased. This review aims to depict the complexity of all the regulatory elements involved in controlling the expression of secondary metabolite gene clusters, ranging from epigenetic control and signal transduction pathways to global and specific transcriptional regulators. Furthermore, we give a short overview on the role of secondary metabolites, focusing on the interaction with other microorganisms in the environment as well as on pathogenic relationships.

The role of autophagy in acute brain injury: A state of flux?

PubMed

Wolf, Michael S; Bayır, Hülya; Kochanek, Patrick M; Clark, Robert S B

2018-04-26

It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

PubMed

Vauzour, David; Houseman, Emily J; George, Trevor W; Corona, Giulia; Garnotel, Roselyne; Jackson, Kim G; Sellier, Christelle; Gillery, Philippe; Kennedy, Orla B; Lovegrove, Julie A; Spencer, Jeremy P E

2010-04-01

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

Spectroscopic Studies of the Super Relaxed State of Skeletal Muscle

PubMed Central

Naber, Nariman; Pate, Edward; Canton, Marcella; Reggiani, Carlo; Cooke, Roger

2016-01-01

In the super-relaxed state of myosin, ATPase activity is strongly inhibited by binding of the myosin heads to the core of the thick filament in a structure known as the interacting-heads motif. In the disordered relaxed state myosin heads are not bound to the core of the thick filament and have an ATPase rate that is 10 fold greater. In the interacting-heads motif the two regulatory light chains appear to bind to each other. We have made single cysteine mutants of the regulatory light chain, placed both paramagnetic and fluorescent probes on them, and exchanged them into skinned skeletal muscle fibers. Many of the labeled light chains tended to disrupt the stability of the super-relaxed state, and showed spectral changes in the transition from the disordered relaxed state to the super-relaxed state. These data support the putative interface between the two regulatory light chains identified by cryo electron microscopy and show that both the divalent cation bound to the regulatory light chain and the N-terminus of the regulatory light chain play a role in the stability of the super-relaxed state. One probe showed a shift to shorter wavelengths in the super-relaxed state such that a ratio of intensities at 440nm to that at 520nm provided a measure of the population of the super-relaxed state amenable for high throughput screens for finding potential pharmaceuticals. The results provide a proof of concept that small molecules that bind to this region can destabilize the super-relaxed state and provide a method to search for small molecules that do so leading to a potentially effective treatment for Type 2 diabetes and obesity. PMID:27479128

Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

PubMed

Tsai, Ching-Chung; Tey, Shu-Leei; Lee, Ming-Che; Liu, Ching-Wen; Su, Yu-Tsun; Huang, Shih-Che

2018-04-01

Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia. Copyright © 2018 Elsevier GmbH. All rights reserved.

Chloride channel function is linked to epithelium-dependent airway relaxation.

PubMed

Fortner, C N; Lorenz, J N; Paul, R J

2001-02-01

We previously reported that substance P (SP) and ATP evoke transient, epithelium-dependent relaxation of mouse tracheal smooth muscle. Since both SP and ATP are known to evoke transepithelial Cl- secretion across epithelial monolayers, we tested the hypothesis that epithelium-dependent relaxation of mouse trachea depends on Cl- channel function. In perfused mouse tracheas, the responses to SP and ATP were both inhibited by the Cl- channel inhibitors diphenylamine-2-carboxylate and 5-nitro-2-(3-phenylpropylamino)benzoate. Relaxation to ATP or SP was unaffected by 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), and relaxation to SP was unaffected by either DIDS or DNDS. Replacing Cl- in the buffer solutions with the impermeable anion gluconate on both sides of the trachea inhibited relaxation to SP or ATP. In contrast, increasing the gradient for Cl- secretion using Cl- free medium only in the tracheal lumen enhanced the relaxation to SP or ATP. We conclude that Cl- channel function is linked to receptor-mediated, epithelium-dependent relaxation. The finding that relaxation to SP was not blocked by DIDS suggested the involvement of a DIDS-insensitive Cl- channel, potentially the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. To test this hypothesis, we evaluated tracheas from CFTR-deficient mice and found that the peak relaxation to SP or ATP was not significantly different from those responses in wild-type littermates. This suggests that a DIDS-insensitive Cl- channel other than CFTR is active in the SP response. This work introduces a possible role for Cl- pathways in the modulation of airway smooth muscle function and may have implications for fundamental studies of airway function as well as therapeutic approaches to pulmonary disease.

Secondary relaxation dynamics in rigid glass-forming molecular liquids with related structures.

PubMed

Li, Xiangqian; Wang, Meng; Liu, Riping; Ngai, Kia L; Tian, Yongjun; Wang, Li-Min; Capaccioli, Simone

2015-09-14

The dielectric relaxation in three glass-forming molecular liquids, 1-methylindole (1MID), 5H-5-Methyl-6,7-dihydrocyclopentapyrazine (MDCP), and Quinaldine (QN) is studied focusing on the secondary relaxation and its relation to the structural α-relaxation. All three glass-formers are rigid and more or less planar molecules with related chemical structures but have dipoles of different strengths at different locations. A strong and fast secondary relaxation is detected in the dielectric spectra of 1MID, while no resolved β-relaxation is observed in MDCP and QN. If the observed secondary relaxation in 1MID is identified with the Johari-Goldstein (JG) β-relaxation, then apparently the relation between the α- and β-relaxation frequencies of 1MID is not in accord with the Coupling Model (CM). The possibility of the violation of the prediction in 1MID as due to either the formation of hydrogen-bond induced clusters or the involvement of intramolecular degree of freedom is ruled out. The violation is explained by the secondary relaxation originating from the in-plane rotation of the dipole located on the plane of the rigid molecule, contributing to dielectric loss at higher frequencies and more intense than the JG β-relaxation generated by the out-of-plane rotation. MDCP has smaller dipole moment located in the plane of the molecule; however, presence of the change of curvature of dielectric loss, ε″(f), at some frequency on the high-frequency flank of the α-relaxation reveals the JG β-relaxation in MDCP and which is in accord with the CM prediction. QN has as large an in-plane dipole moment as 1MID, and the absence of the resolved secondary relaxation is explained by the smaller coupling parameter than the latter in the framework of the CM.

MIDAS: a database-searching algorithm for metabolite identification in metabolomics.

PubMed

Wang, Yingfeng; Kora, Guruprasad; Bowen, Benjamin P; Pan, Chongle

2014-10-07

A database searching approach can be used for metabolite identification in metabolomics by matching measured tandem mass spectra (MS/MS) against the predicted fragments of metabolites in a database. Here, we present the open-source MIDAS algorithm (Metabolite Identification via Database Searching). To evaluate a metabolite-spectrum match (MSM), MIDAS first enumerates possible fragments from a metabolite by systematic bond dissociation, then calculates the plausibility of the fragments based on their fragmentation pathways, and finally scores the MSM to assess how well the experimental MS/MS spectrum from collision-induced dissociation (CID) is explained by the metabolite's predicted CID MS/MS spectrum. MIDAS was designed to search high-resolution tandem mass spectra acquired on time-of-flight or Orbitrap mass spectrometer against a metabolite database in an automated and high-throughput manner. The accuracy of metabolite identification by MIDAS was benchmarked using four sets of standard tandem mass spectra from MassBank. On average, for 77% of original spectra and 84% of composite spectra, MIDAS correctly ranked the true compounds as the first MSMs out of all MetaCyc metabolites as decoys. MIDAS correctly identified 46% more original spectra and 59% more composite spectra at the first MSMs than an existing database-searching algorithm, MetFrag. MIDAS was showcased by searching a published real-world measurement of a metabolome from Synechococcus sp. PCC 7002 against the MetaCyc metabolite database. MIDAS identified many metabolites missed in the previous study. MIDAS identifications should be considered only as candidate metabolites, which need to be confirmed using standard compounds. To facilitate manual validation, MIDAS provides annotated spectra for MSMs and labels observed mass spectral peaks with predicted fragments. The database searching and manual validation can be performed online at http://midas.omicsbio.org.

40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... chemical properties of the metabolite or degradate. (B) Data regarding structurally analogous chemicals. (C) Data regarding chemical reactivity of the metabolite or degradate and structurally analogous substances... any person described in § 159.158(a) that the metabolite or degradate, or analogous chemicals, may...

40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... chemical properties of the metabolite or degradate. (B) Data regarding structurally analogous chemicals. (C) Data regarding chemical reactivity of the metabolite or degradate and structurally analogous substances... any person described in § 159.158(a) that the metabolite or degradate, or analogous chemicals, may...

Electron spin relaxation in two polymorphic structures of GaN

NASA Astrophysics Data System (ADS)

Kang, Nam Lyong

2015-03-01

The relaxation process of electron spin in systems of electrons interacting with piezoelectric deformation phonons that are mediated through spin-orbit interactions was interpreted from a microscopic point of view using the formula for the electron spin relaxation times derived by a projection-reduction method. The electron spin relaxation times in two polymorphic structures of GaN were calculated. The piezoelectric material constant for the wurtzite structure obtained by a comparison with a previously reported experimental result was {{P}pe}=1.5 × {{10}29} eV {{m}-1}. The temperature and magnetic field dependence of the relaxation times for both wurtzite and zinc-blende structures were similar, but the relaxation times in zinc-blende GaN were smaller and decreased more rapidly with increasing temperature and magnetic field than that in wurtzite GaN. This study also showed that the electron spin relaxation for wurtzite GaN at low density could be explained by the Elliot-Yafet process but not for zinc-blende GaN in the metallic regime.

Interrelation of creep and relaxation: a modeling approach for ligaments.

PubMed

Lakes, R S; Vanderby, R

1999-12-01

Experimental data (Thornton et al., 1997) show that relaxation proceeds more rapidly (a greater slope on a log-log scale) than creep in ligament, a fact not explained by linear viscoelasticity. An interrelation between creep and relaxation is therefore developed for ligaments based on a single-integral nonlinear superposition model. This interrelation differs from the convolution relation obtained by Laplace transforms for linear materials. We demonstrate via continuum concepts of nonlinear viscoelasticity that such a difference in rate between creep and relaxation phenomenologically occurs when the nonlinearity is of a strain-stiffening type, i.e., the stress-strain curve is concave up as observed in ligament. We also show that it is inconsistent to assume a Fung-type constitutive law (Fung, 1972) for both creep and relaxation. Using the published data of Thornton et al. (1997), the nonlinear interrelation developed herein predicts creep behavior from relaxation data well (R > or = 0.998). Although data are limited and the causal mechanisms associated with viscoelastic tissue behavior are complex, continuum concepts demonstrated here appear capable of interrelating creep and relaxation with fidelity.

Topology Synthesis of Structures Using Parameter Relaxation and Geometric Refinement

NASA Technical Reports Server (NTRS)

Hull, P. V.; Tinker, M. L.

2007-01-01

Typically, structural topology optimization problems undergo relaxation of certain design parameters to allow the existence of intermediate variable optimum topologies. Relaxation permits the use of a variety of gradient-based search techniques and has been shown to guarantee the existence of optimal solutions and eliminate mesh dependencies. This Technical Publication (TP) will demonstrate the application of relaxation to a control point discretization of the design workspace for the structural topology optimization process. The control point parameterization with subdivision has been offered as an alternative to the traditional method of discretized finite element design domain. The principle of relaxation demonstrates the increased utility of the control point parameterization. One of the significant results of the relaxation process offered in this TP is that direct manufacturability of the optimized design will be maintained without the need for designer intervention or translation. In addition, it will be shown that relaxation of certain parameters may extend the range of problems that can be addressed; e.g., in permitting limited out-of-plane motion to be included in a path generation problem.

Predicting the effect of relaxation during frequency-selective adiabatic pulses

NASA Astrophysics Data System (ADS)

Pfaff, Annalise R.; McKee, Cailyn E.; Woelk, Klaus

2017-11-01

Adiabatic half and full passages are invaluable for achieving uniform, B1-insensitive excitation or inversion of macroscopic magnetization across a well-defined range of NMR frequencies. To accomplish narrow frequency ranges with adiabatic pulses (<100 Hz), long pulse durations at low RF power levels are necessary, and relaxation during these pulses may no longer be negligible. A numerical, discrete recursive combination of the Bloch equations for longitudinal and transverse relaxation with the optimized equation for adiabatic angular motion of magnetization is used to calculate the trajectory of magnetization including its relaxation during adiabatic hyperbolic secant pulses. The agreement of computer-calculated data with experimental results demonstrates that, in non-viscous, small-molecule fluids, it is possible to model magnetization and relaxation by considering standard T1 and T2 relaxation in the traditional rotating frame. The proposed model is aimed at performance optimizations of applications in which these pulses are employed. It differs from previous reports which focused on short high-power adiabatic pulses and relaxation that is governed by dipole-dipole interactions, cross polarization, or chemical exchange.

Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism.

PubMed

Krishnaiah, Saikumari Y; Wu, Gang; Altman, Brian J; Growe, Jacqueline; Rhoades, Seth D; Coldren, Faith; Venkataraman, Anand; Olarerin-George, Anthony O; Francey, Lauren J; Mukherjee, Sarmistha; Girish, Saiveda; Selby, Christopher P; Cal, Sibel; Er, Ubeydullah; Sianati, Bahareh; Sengupta, Arjun; Anafi, Ron C; Kavakli, I Halil; Sancar, Aziz; Baur, Joseph A; Dang, Chi V; Hogenesch, John B; Weljie, Aalim M

2017-04-04

The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes. These 18 metabolites were enriched in methylation and amino acid pathways. To assess clock dependence of these rhythms, we used genetic perturbation. BMAL1 knockdown diminished metabolite rhythms, while CRY1 or CRY2 perturbation generally shortened or lengthened rhythms, respectively. Surprisingly, CRY1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite from transcriptional rhythms, with potential impact on nutrient sensing in vivo. These results provide the first comprehensive views of circadian liver and cell-autonomous metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

On the non-exponentiality of the dielectric Debye-like relaxation of monoalcohols

NASA Astrophysics Data System (ADS)

Arrese-Igor, S.; Alegría, A.; Colmenero, J.

2017-03-01

We have investigated the Debye-like relaxation in a series of monoalcohols (MAs) by broadband dielectric spectroscopy and thermally stimulated depolarization current techniques in order to get further insight on the time dispersion of this intriguing relaxation. Results indicate that the Debye-like relaxation of MAs is not always of exponential type and conforms well to a dispersion of Cole-Davidson type. Apart from the already reported non-exponentiality of the Debye-like relaxation in 2-hexyl-1-decanol and 2-butyl-1-octanol, a detailed analysis of the dielectric permittivity of 5-methyl-3-heptanol shows that this MA also presents some extent of dispersion on its Debye-like relaxation which strongly depends on the temperature. Results suggest that the non-exponential character of the Debye-like relaxation might be a general characteristic in the case of not so intense Debye-like relaxations relative to the α relaxation. Finally, we briefly discuss on the T-dependence and possible origin for the observed dispersion.

The Interplay of Preference, Familiarity and Psychophysical Properties in Defining Relaxation Music.

PubMed

Tan, Xueli; Yowler, Charles J; Super, Dennis M; Fratianne, Richard B

2012-01-01

The stress response has been well documented in past music therapy literature. However, hypometabolism, or the relaxation response, has received much less attention. Music therapists have long utilized various music-assisted relaxation techniques with both live and recorded music to elicit such a response. The ongoing proliferations of relaxation music through commercial media and the dire lack of evidence to support such claims warrant attention from healthcare professionals and music therapists. The purpose of these 3 studies was to investigate the correlational relationships between 12 psychophysical properties of music, preference, familiarity, and degree of perceived relaxation in music. Fourteen music therapists recommended and analyzed 30 selections of relaxation music. A group of 80 healthy adults then rated their familiarity, preference, and degree of perceived relaxation in the music. The analysis provided a detailed description of the intrinsic properties in music that were perceived to be relaxing by listeners. These properties included tempo, mode, harmonic, rhythmic, instrumental, and melodic complexities, timbre, vocalization/lyrics, pitch range, dynamic variations, and contour. In addition, music preference was highly correlated with listeners' perception of relaxation in music for both music therapists and healthy adults. The correlation between familiarity and degree of relaxation reached significance in the healthy adult group. Results from this study provided an in-depth operational definition of the intrinsic parameters in relaxation music and also highlighted the importance of preference and familiarity in eliciting the relaxation response.

Electron spin relaxation in a transition-metal dichalcogenide quantum dot

NASA Astrophysics Data System (ADS)

Pearce, Alexander J.; Burkard, Guido

2017-06-01

We study the relaxation of a single electron spin in a circular quantum dot in a transition-metal dichalcogenide monolayer defined by electrostatic gating. Transition-metal dichalcogenides provide an interesting and promising arena for quantum dot nano-structures due to the combination of a band gap, spin-valley physics and strong spin-orbit coupling. First we will discuss which bound state solutions in different B-field regimes can be used as the basis for qubits states. We find that at low B-fields combined spin-valley Kramers qubits to be suitable, while at large magnetic fields pure spin or valley qubits can be envisioned. Then we present a discussion of the relaxation of a single electron spin mediated by electron-phonon interaction via various different relaxation channels. In the low B-field regime we consider the spin-valley Kramers qubits and include impurity mediated valley mixing which will arise in disordered quantum dots. Rashba spin-orbit admixture mechanisms allow for relaxation by in-plane phonons either via the deformation potential or by piezoelectric coupling, additionally direct spin-phonon mechanisms involving out-of-plane phonons give rise to relaxation. We find that the relaxation rates scale as \\propto B 6 for both in-plane phonons coupling via deformation potential and the piezoelectric effect, while relaxation due to the direct spin-phonon coupling scales independant to B-field to lowest order but depends strongly on device mechanical tension. We will also discuss the relaxation mechanisms for pure spin or valley qubits formed in the large B-field regime.

Glass transition and relaxation processes of nanocomposite polymer electrolytes.

PubMed

Money, Benson K; Hariharan, K; Swenson, Jan

2012-07-05

This study focus on the effect of δ-Al(2)O(3) nanofillers on the dc-conductivity, glass transition, and dielectric relaxations in the polymer electrolyte (PEO)(4):LiClO(4). The results show that there are three dielectric relaxation processes, α, β, and γ, in the systems, although the structural α-relaxation is hidden in the strong conductivity contribution and could therefore not be directly observed. However, by comparing an enhanced dc-conductivity, by approximately 2 orders of magnitude with 4 wt % δ-Al(2)O(3) added, with a decrease in calorimetric glass transition temperature, we are able to conclude that the dc-conductivity is directly coupled to the hidden α-relaxation, even in the presence of nanofillers (at least in the case of δ-Al(2)O(3) nanofillers at concentrations up to 4 wt %). This filler induced speeding up of the segmental polymer dynamics, i.e., the α-relaxation, can be explained by the nonattractive nature of the polymer-filler interactions, which enhance the "free volume" and mobility of polymer segments in the vicinity of filler surfaces.

Thermally induced magnetic relaxation in square artificial spin ice

DOE PAGES

Andersson, M. S.; Pappas, S. D.; Stopfel, H.; ...

2016-11-24

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here in this paper, we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system $-$ square artificial spin ice $-$ we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Usingmore » time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.« less

Thermally induced magnetic relaxation in square artificial spin ice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, M. S.; Pappas, S. D.; Stopfel, H.

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here in this paper, we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system $-$ square artificial spin ice $-$ we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Usingmore » time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.« less

Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

PubMed Central

Villas-Boas, Silas G.; Aggio, Raphael

2017-01-01

Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells. PMID:29065530

Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study.

PubMed

Wilson, Jack H; Criss, Amy H; Spangler, Sean A; Walukevich, Katherine; Hewett, Sandra

2017-10-01

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7-10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

Suppression of Raman electron spin relaxation of radicals in crystals. Comparison of Cu2+ and free radical relaxation in triglycine sulfate and Tutton salt single crystals.

PubMed

Hoffmann, S K; Goslar, J; Lijewski, S

2011-08-31

Electron spin-lattice relaxation was measured by the electron spin echo method in a broad temperature range above 4.2 K for Cu(2+) ions and free radicals produced by ionizing radiation in triglycine sulfate (TGS) and Tutton salt (NH4)(2)Zn(SO4)2 ⋅ 6H2O crystals. Localization of the paramagnetic centres in the crystal unit cells was determined from continuous wave electron paramagnetic resonance spectra. Various spin relaxation processes and mechanisms are outlined. Cu(2+) ions relax fast via two-phonon Raman processes in both crystals involving the whole phonon spectrum of the host lattice. This relaxation is slightly slower for TGS where Cu(2+) ions are in the interstitial position. The ordinary Raman processes do not contribute to the radical relaxation which relaxes via the local phonon mode. The local mode lies within the acoustic phonon band for radicals in TGS but within the optical phonon range in (NH4)(2)Zn(SO4)2 ⋅ 6H2O. In the latter the cross-relaxation was considered. A lack of phonons around the radical molecules suggested a local crystal amorphisation produced by x- or γ-rays.

Relaxation of ferromagnetic nanoparticles in macrophages: In vitro and in vivo studies

NASA Astrophysics Data System (ADS)

Möller, Winfried; Takenaka, Shinji; Buske, Norbert; Felten, Kathrin; Heyder, Joachim

2005-05-01

The relaxation characteristics of magnetic nanoparticles (CoFe 2O 4) were investigated in J774A.1 macrophages and after voluntary inhalation. In dry form 25% of the particles showed Néel relaxation. Relaxation in macrophages occurred within minutes and could be inhibited by fixation, showing Brownian relaxation and intracellular transport processes. Relaxation in the lung happened similarly, but was dependent on the time after deposition. The particles were cleared from the lung within 2 weeks.

Efficient and optimized identification of generalized Maxwell viscoelastic relaxation spectra

PubMed Central

Babaei, Behzad; Davarian, Ali; Pryse, Kenneth M.; Elson, Elliot L.; Genin, Guy M.

2017-01-01

Viscoelastic relaxation spectra are essential for predicting and interpreting the mechanical responses of materials and structures. For biological tissues, these spectra must usually be estimated from viscoelastic relaxation tests. Interpreting viscoelastic relaxation tests is challenging because the inverse problem is expensive computationally. We present here an efficient algorithm that enables rapid identification of viscoelastic relaxation spectra. The algorithm was tested against trial data to characterize its robustness and identify its limitations and strengths. The algorithm was then applied to identify the viscoelastic response of reconstituted collagen, revealing an extensive distribution of viscoelastic time constants. PMID:26523785

Efficient and optimized identification of generalized Maxwell viscoelastic relaxation spectra.

PubMed

Babaei, Behzad; Davarian, Ali; Pryse, Kenneth M; Elson, Elliot L; Genin, Guy M

2015-03-01

Viscoelastic relaxation spectra are essential for predicting and interpreting the mechanical responses of materials and structures. For biological tissues, these spectra must usually be estimated from viscoelastic relaxation tests. Interpreting viscoelastic relaxation tests is challenging because the inverse problem is expensive computationally. We present here an efficient algorithm that enables rapid identification of viscoelastic relaxation spectra. The algorithm was tested against trial data to characterize its robustness and identify its limitations and strengths. The algorithm was then applied to identify the viscoelastic response of reconstituted collagen, revealing an extensive distribution of viscoelastic time constants. Copyright © 2015 Elsevier Ltd. All rights reserved.

A-FABP and oxidative stress underlie the impairment of endothelium-dependent relaxations to serotonin and the intima-medial thickening in the porcine coronary artery with regenerated endothelium.

PubMed

Chan, Calvin K; Zhao, Yingzi; Liao, Song Yan; Zhang, Yue Lin; Lee, Mary Y K; Xu, Aimin; Tse, Hung Fat; Vanhoutte, Paul M

2013-01-16

Experiments were designed to determine the cause of the selective dysfunction of G(i) proteins, characterized by a reduced endothelium-dependent relaxation to serotonin (5-hydroxytryptamine), in coronary arteries lined with regenerated endothelial cells. Part of the endothelium of the left anterior descending coronary artery of female pigs was removed in vivo to induce regeneration. The animals were treated chronically with vehicle (control), apocynin (antioxidant), or BMS309403 (A-FABP inhibitor) for 28 days before functional examination and histological analysis of segments of coronary arteries with native or regenerated endothelium of the same hearts. Isometric tension was recorded in organ chambers and cumulative concentration-relaxation curves obtained in response to endothelium-dependent [serotonin (G(i) protein mediated activation of eNOS) and bradykinin (G(q) protein mediated activation of eNOS)] and independent [detaNONOate (cGMP-mediated), isoproterenol (cAMP-mediated)] vasodilators. The two inhibitors tested did not acutely affect relaxations of preparations with either native or regenerated endothelium. In the chronically treated groups, however, both apocynin and BMS309403 abolished the reduction in relaxation to serotonin in segments covered with regenerated endothelium and prevented the intima-medial thickening caused by endothelial regeneration, without affecting responses to bradykinin or endothelium-independent agonists (detaNONOate and isoproterenol). Thus, inhibition of either oxidative stress or A-FABP likely prevents both the selective dysfunction of G(i) protein mediated relaxation to serotonin and the neointimal thickening resulting from endothelial regeneration.

Investigation of metabolites for estimating blood deposition time.

PubMed

Lech, Karolina; Liu, Fan; Davies, Sarah K; Ackermann, Katrin; Ang, Joo Ern; Middleton, Benita; Revell, Victoria L; Raynaud, Florence J; Hoveijn, Igor; Hut, Roelof A; Skene, Debra J; Kayser, Manfred

2018-01-01

Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor's alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.

Difference and similarity of dielectric relaxation processes among polyols

NASA Astrophysics Data System (ADS)

Minoguchi, Ayumi; Kitai, Kei; Nozaki, Ryusuke

2003-09-01

Complex permittivity measurements were performed on sorbitol, xylitol, and sorbitol-xylitol mixture in the supercooled liquid state in an extremely wide frequency range from 10 μHz to 500 MHz at temperatures near and above the glass transition temperature. We determined detailed behavior of the relaxation parameters such as relaxation frequency and broadening against temperature not only for the α process but also for the β process above the glass transition temperature, to the best of our knowledge, for the first time. Since supercooled liquids are in the quasi-equilibrium state, the behavior of all the relaxation parameters for the β process can be compared among the polyols as well as those for the α process. The relaxation frequencies of the α processes follow the Vogel-Fulcher-Tammann manner and the loci in the Arrhenius diagram are different corresponding to the difference of the glass transition temperatures. On the other hand, the relaxation frequencies of the β processes, which are often called as the Johari-Goldstein processes, follow the Arrhenius-type temperature dependence. The relaxation parameters for the β process are quite similar among the polyols at temperatures below the αβ merging temperature, TM. However, they show anomalous behavior near TM, which depends on the molecular size of materials. These results suggest that the origin of the β process is essentially the same among the polyols.

Relaxational effects in radiating stellar collapse

NASA Astrophysics Data System (ADS)

Govender, Megan; Maartens, Roy; Maharaj, Sunil D.

1999-12-01

Relaxational effects in stellar heat transport can in many cases be significant. Relativistic Fourier-Eckart theory is inherently quasi-stationary, and cannot incorporate these effects. The effects are naturally accounted for in causal relativistic thermodynamics, which provides an improved approximation to kinetic theory. Recent results, based on perturbations of a static star, show that relaxation effects can produce a significant increase in the central temperature and temperature gradient for a given luminosity. We use a simple stellar model that allows for non-perturbative deviations from staticity, and confirms qualitatively the predictions of the perturbative models.

Vibrational relaxation in hypersonic flow fields

NASA Technical Reports Server (NTRS)

Meador, Willard E.; Miner, Gilda A.; Heinbockel, John H.

1993-01-01

Mathematical formulations of vibrational relaxation are derived from first principles for application to fluid dynamic computations of hypersonic flow fields. Relaxation within and immediately behind shock waves is shown to be substantially faster than that described in current numerical codes. The result should be a significant reduction in nonequilibrium radiation overshoot in shock layers and in radiative heating of hypersonic vehicles; these results are precisely the trends needed to bring theoretical predictions more in line with flight data. Errors in existing formulations are identified and qualitative comparisons are made.

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

PubMed

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

[Synthetic biology toward microbial secondary metabolites and pharmaceuticals].

PubMed

Wu, Lin-Zhuan; Hong, Bin

2013-02-01

Microbial secondary metabolites are one of the major sources of anti-bacterial, anti-fungal, antitumor, anti-virus and immunosuppressive agents for clinical use. Present challenges in microbial pharmaceutical development are the discovery of novel secondary metabolites with significant biological activities, improving the fermentation titers of industrial microbial strains, and production of natural product drugs by re-establishing their biosynthetic pathways in suitable microbial hosts. Synthetic biology, which is developed from systematic biology and metabolic engineering, provides a significant driving force for microbial pharmaceutical development. The review describes the major applications of synthetic biology in novel microbial secondary metabolite discovery, improved production of known secondary metabolites and the production of some natural drugs in genetically modified or reconstructed model microorganisms.

Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

PubMed

Ayil-Gutiérrez, Benjamin A; Villegas-Mendoza, Jesús M; Santes-Hernndez, Zuridai; Paz-González, Alma D; Mireles-Martínez, Maribel; Rosas-García, Ninfa M; Rivera, Gildardo

2015-11-01

The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents (ethyl acetate, ethanol, and water) and metabolites (psoralen, 2- undecanone and rutin) against Spodoptera frugiperda was evaluated. Metabolites levels in extracts were quantified by HPLC and GC. Ethyl acetate and ethanol extracts showed 94% and 78% mortality, respectively. Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone (87.9 µmoles mg(-1) DW), psoralen (3.6 µmoles mg(-1) DW) and rutin (0.001 pmoles mg(-1) DW). We suggest that these concentrations of 2-undecanone and psoralen in R. graveolens leaf tissue extracts could be responsible for S. frugiperda mortality.

Cellular stress created by intermediary metabolite imbalances.

PubMed

Lee, Sang Jun; Trostel, Andrei; Le, Phuoc; Harinarayanan, Rajendran; Fitzgerald, Peter C; Adhya, Sankar

2009-11-17

Small molecules generally activate or inhibit gene transcription as externally added substrates or as internally accumulated end-products, respectively. Rarely has a connection been made that links an intracellular intermediary metabolite as a signal of gene expression. We report that a perturbation in the critical step of a metabolic pathway--the D-galactose amphibolic pathway--changes the dynamics of the pathways leading to accumulation of the intermediary metabolite UDP-galactose. This accumulation causes cell stress and transduces signals that alter gene expression so as to cope with the stress by restoring balance in the metabolite pool. This underscores the importance of studying the global effects of alterations in the level of intermediary metabolites in causing stress and coping with it by transducing signals to genes to reach a stable state of equilibrium (homeostasis). Such studies are an essential component in the integration of metabolomics, proteomics, and transcriptomics.

Characterization of structural relaxation in inorganic glasses using length dilatometry

NASA Astrophysics Data System (ADS)

Koontz, Erick

The processes that govern how a glass relaxes towards its thermodynamic quasi-equilibrium state are major factors in understanding glass behavior near the glass transition region, as characterized by the glass transition temperature (Tg). Intrinsic glass properties such as specific volume, enthalpy, entropy, density, etc. are used to map the behavior of the glass network below in and near the transition region. The question of whether a true thermodynamic second order phase transition takes place in the glass transition region is another pending question. Linking viscosity behavior to entropy, or viewing the glass configuration as an energy landscape are just a couple of the most prevalent methods used for attempting to understand the glass transition. The structural relaxation behavior of inorganic glasses is important for more than scientific reasons, many commercial glass processing operations including glass melting and certain forms of optical fabrication include significant time spent in the glass transition region. For this reason knowledge of structural relaxation processes can, at a minimum, provide information for annealing duration of melt-quenched glasses. The development of a predictive model for annealing time prescription has the potential to save glass manufacturers significant time and money as well as increasing volume throughput. In optical hot forming processes such as precision glass molding, molded optical components can significantly change in shape upon cooling through the glass transition. This change in shape is not scientifically predictable as of yet though manufacturers typically use empirical rules developed in house. The classification of glass behavior in the glass transition region would allow molds to be accurately designed and save money for the producers. The work discussed in this dissertation is comprised of the development of a dilatometric measurement and characterization method of structural relaxation. The measurement and

The influence of dielectric relaxation on intramolecular electron transfer

NASA Astrophysics Data System (ADS)

Heitele, H.; Michel-Beyerle, M. E.; Finckh, P.

1987-07-01

An unusually strong temperature dependence on the intramolecular electron-transfer rate has been observed for bridged donor-acceptor compounds in propylene glycol solution. In the frame of recent electron-transfer theories this effect reflects the influence of dielectric relaxation dynamics on electron transfer. With increasing dielectric relaxation time a smooth transition from non-adiabatic to solvent-controlled adiabatic behaviour is observed. The electron transfer rate in the solvent-controlled adiabatic limit is dominated by an inhomogeneous distribution of relaxation times.

Longitudinal relaxation of initially straight flexible and stiff polymers

NASA Astrophysics Data System (ADS)

Dimitrakopoulos, Panagiotis; Dissanayake, Inuka

2004-11-01

The present talk considers the relaxation of a single flexible or stiff polymer chain from an initial straight configuration in a viscous solvent. This problem commonly arises when strong flows are turned off in both industrial and biological applications. The problem is also motivated by recent experiments with single biopolymer molecules relaxing after being fully extended by applied forces as well as by the recent development of micro-devices involving stretched tethered biopolymers. Our results are applicable to a wide array of synthetic polymers such as polyacrylamides, Kevlar and polyesters as well as biopolymers such as DNA, actin filaments, microtubules and MTV. In this talk we discuss the mechanism of the polymer relaxation as was revealed through Brownian Dynamics simulations covering a broad range of time scales and chain stiffness. After the short-time free diffusion, the chain's longitudinal reduction at early intermediate times is shown to constitute a universal behavior for any chain stiffness caused by a quasi-steady relaxation of tensions associated with the deforming action of the Brownian forces. Stiff chains are shown to exhibit a late intermediate-time longitudinal reduction associated with a relaxation of tensions affected by the deforming Brownian and the restoring bending forces. The longitudinal and transverse relaxations are shown to obey different laws, i.e. the chain relaxation is anisotropic at all times. In the talk, we show how from the knowledge of the relaxation mechanism, we can predict and explain the polymer properties including the polymer stress and the solution birefringence. In addition, a generalized stress-optic law is derived valid for any time and chain stiffness. All polymer properties which depend on the polymer length are shown to exhibit two intermediate-time behaviors with the early one to constitute a universal behavior for any chain stiffness. This work was supported in part by the Minta Martin Research Fund. The

Predictors of mitral annulus early diastolic velocity: impact of long-axis function, ventricular filling pattern, and relaxation

PubMed Central

Popović, Zoran B.; Desai, Milind Y.; Buakhamsri, Adisai; Puntawagkoon, Chirapa; Borowski, Allen; Levine, Benjamin D.; Tang, Wilson W.H.; Thomas, James D.

2011-01-01

Aims Although left ventricular (LV) relaxation is well recognized as a predictor of mitral annulus (MA) early diastolic (E′) velocity, its significance relative to other predictors of E′ is less well understood. Methods and results We assessed 40 healthy volunteers, 43 patients with acutely decompensated chronic systolic heart failure (HF), and 36 patients with hypertrophic obstructive cardiomyopathy (HOCM) using echocardiography and right or left heart catheterization. Data were obtained at baseline. In addition, in healthy volunteers haemodynamics were varied by graded saline infusion and low body negative pressure, while in HF patients it was varied by vasoactive drug treatment. E- and A-wave velocity (E/A) ratio of the mitral valve inflow, systolic MA velocity integral (s′ integral) and E′ and late velocity (A′) of lateral and septal MA pulsed wave velocities were assessed by echocardiography. Time constant of isovolumic pressure decay τ0) was calculated from isovolumic relaxation time/[ln(aortic dicrotic notch pressure) – ln(LV filling pressure)]. In all three groups, s′ integral was the strongest predictor of E′ (partial r= 0.53–0.79; 0.81 for three groups combined), followed by E/A ratio (partial r= 0.10–0.78; 0.26 for all groups combined) and τ0 (partial r= −0.1 to 0.023; −0.21 for all groups combined). Conclusion In healthy adults, patients with systolic HF, or patients with HOCM, E′ is related to LV long-axis function and E/A ratio, a global marker of LV filling. E′ appears less sensitive to LV relaxation. PMID:21865226

Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonsart, Julien, E-mail: julien.fonsart@lrb.aphp.f; CNRS, UMR 7157, Paris F-75006; INSERM, U705, Paris F-75006

The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC{sub last} and C{sub max} were 1.6- tomore » 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C{sub max} and AUC{sub last} were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC{sub last} and t{sub 1/2} were 50% higher in females given MDMA (1 mg/kg iv). MDA C{sub max} and AUC{sub last} were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC{sub last} of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.« less

Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum, and thalamus of the rat.

PubMed

Kaplan, Kimberly A; Chiu, Veronica M; Lukus, Peter A; Zhang, Xing; Siems, William F; Schenk, James O; Hill, Herbert H

2013-02-01

We report results of studies of global and targeted neuronal metabolomes by ambient pressure ion mobility mass spectrometry. The rat frontal cortex, striatum, and thalamus were sampled from control nontreated rats and those treated with acute cocaine or pargyline. Quantitative evaluations were made by standard additions or isotopic dilution. The mass detection limit was ~100 pmol varying with the analyte. Targeted metabolites of dopamine, serotonin, and glucose followed the rank order of distribution expected between the anatomical areas. Data was evaluated by principal component analysis on 764 common metabolites (identified by m/z and reduced mobility). Differences between anatomical areas and treatment groups were observed for 53 % of these metabolites using principal component analysis. Global and targeted metabolic differences were observed between the three anatomical areas with contralateral differences between some areas. Following drug treatments, global and targeted metabolomes were found to shift relative to controls and still maintained anatomical differences. Pargyline reduced 3,4-dihydroxyphenylacetic acid below detection limits, and 5-HIAA varied between anatomical regions. Notable findings were: (1) global metabolomes were different between anatomical areas and were altered by acute cocaine providing a broad but targeted window of discovery for metabolic changes produced by drugs of abuse; (2) quantitative analysis was demonstrated using isotope dilution and standard addition; (3) cocaine changed glucose and biogenic amine metabolism in the anatomical areas tested; and (4) the largest effect of cocaine was on the glycolysis metabolome in the thalamus confirming inferences from previous positron emission tomography studies using 2-deoxyglucose.

relaxGUI: a new software for fast and simple NMR relaxation data analysis and calculation of ps-ns and μs motion of proteins.

PubMed

Bieri, Michael; d'Auvergne, Edward J; Gooley, Paul R

2011-06-01

Investigation of protein dynamics on the ps-ns and μs-ms timeframes provides detailed insight into the mechanisms of enzymes and the binding properties of proteins. Nuclear magnetic resonance (NMR) is an excellent tool for studying protein dynamics at atomic resolution. Analysis of relaxation data using model-free analysis can be a tedious and time consuming process, which requires good knowledge of scripting procedures. The software relaxGUI was developed for fast and simple model-free analysis and is fully integrated into the software package relax. It is written in Python and uses wxPython to build the graphical user interface (GUI) for maximum performance and multi-platform use. This software allows the analysis of NMR relaxation data with ease and the generation of publication quality graphs as well as color coded images of molecular structures. The interface is designed for simple data analysis and management. The software was tested and validated against the command line version of relax.

Diffusional mechanisms augment the fluorine magnetic resonance relaxation in paramagnetic perfluorocarbon nanoparticles that provides a “relaxation switch” for detecting cellular endosomal activation

PubMed Central

Hu, Lingzhi; Zhang, Lei; Chen, Junjie; Lanza, Gregory M.; Wickline, Samuel A.

2011-01-01

Purpose To develop a physical model for the 19F relaxation enhancement in paramagnetic perfluorocarbon nanoparticles (PFC NP) and demonstrate its application in monitoring cellular endosomal functionality through a “19F relaxation switch” phenomenon. Materials and Methods An explicit expression for 19F longitudinal relaxation enhancement was derived analytically. Monte-Carlo simulation was performed to confirm the gadolinium induced magnetic field inhomogenity inside the PFC NP. Field dependent T1 measurements for three types of paramagnetic PFC NPs were carried out to validate the theoretical prediction. Based on the physical model, 19F and 1H relaxation properties of macrophage internalized paramagnetic PFC NPs were measured to evaluate the intracellular process of NPs by macrophages in vitro. Results The theoretical description was confirmed experimentally by field-dependent T1 measurements. The shortening of 19F T1 was found to be attributed to the Brownian motion of PFC molecules inside the NP in conjunction with their ability to permeate into the lipid surfactant coating. A dramatic change of 19F T1 was observed upon endocytosis, revealing the transition from intact bound PFC NP to processed constituents. Conclusion The proposed first-principle analysis of 19F spins in paramagnetic PFC NP relates their structural parameters to the special MR relaxation features. The demonstrated “19F relaxation switch” phenomenon is potentially useful for monitoring cellular endosomal functionality. PMID:21761488

Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin-more » (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance

Influence of abiotic stress signals on secondary metabolites in plants

PubMed Central

Ramakrishna, Akula; Ravishankar, Gokare Aswathanarayana

2011-01-01

Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID:22041989

Skeletal Muscle Acute and Chronic Metabolic Response to Essential Amino Acid Supplementation in Hypertriglyceridemic Older Adults

PubMed Central

Marquis, Bryce J; Hurren, Nicholas M; Carvalho, Eugenia; Kim, Il-Young; Schutzler, Scott; Azhar, Gohar; Wolfe, Robert R; Børsheim, Elisabet

2017-01-01

Abstract Background: Supplementation with essential amino acids (EAAs) + arginine is a promising nutritional approach to decrease plasma triglyceride (TG) concentrations, which are an independent risk factor for ischemic heart disease. Objective: The objective of this study was to examine the effects of 8 wk of EAA supplementation on skeletal muscle basal metabolite concentrations and changes in metabolic response to acute EAA intake, with an emphasis on mitochondrial metabolism, in adults with elevated TGs to better understand the mechanisms of lowering plasma TGs. Methods: Older adults with elevated plasma TG concentrations were given 22 g EAAs to ingest acutely before and after an 8-wk EAA supplementation period. Skeletal muscle biopsy samples were collected before and after acute EAA intake, both pre- and postsupplementation (4 biopsy samples), and targeted metabolomic analyses of organic acids and acylcarnitines were conducted on the specimens. Results: Acute EAA intake resulted in increased skeletal muscle acylcarnitine concentrations associated with oxidative catabolism of the supplement components, with the largest increases found in acylcarnitines of branched-chain amino acid oxidative catabolism, including isovaleryl-carnitine (2200%) and 2-methylbutyryl-carnitine (2400%). The chronic EAA supplementation resulted in a 19% decrease in plasma TGs along with accumulation of long-chain acylcarnitines myristoyl- (90%) and stearoyl- (120%) carnitine in skeletal muscle and increases in succinyl-carnitine (250%) and the late-stage tricarboxylic acid cycle intermediates fumarate (44%) and malate (110%). Conclusions: Supplementation with EAAs shows promise as an approach for moderate reduction in plasma TGs. Changes in skeletal muscle metabolites suggest incomplete fatty acid oxidation and increased anaplerosis, which suggests a potential bottleneck in fatty acid metabolism.

Metabolism and metabolites of polychlorinated biphenyls (PCBs)

PubMed Central

Grimm, FA; Hu, D; Kania-Korwel, I; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

2015-01-01

The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed. PMID:25629923

Two-Relaxation-Time Lattice Boltzmann Method for Advective-Diffusive-Reactive Transport

NASA Astrophysics Data System (ADS)

Yan, Z.; Hilpert, M.

2016-12-01

The lattice Boltzmann method (LBM) has been applied to study a wide range of reactive transport in porous and fractured media. The single-relaxation-time (SRT) LBM, employing single relaxation time, is the most popular LBM due to its simplicity of understanding and implementation. Nevertheless, the SRT LBM may suffer from numerical instability for small value of the relaxation time. By contrast, the multiple-relaxation-time (MRT) LBM, employing multiple relaxation times, can improve the numerical stability through tuning the multiple relaxation times, but the complexity of implementing this method restricts its applications. The two-relaxation-time (TRT) LBM, which employs two relaxation times, combines the advantages of SRT and MRT LBMs. The TRT LBM can produce simulations with better accuracy and stability than the SRT one, and is easier to implement than the MRT one. This work evaluated the numerical accuracy and stability of the TRT method by comparing the simulation results with analytical solutions of Gaussian hill transport and Taylor dispersion under different advective velocities. The accuracy generally increased with the tunable relaxation time τ, and the stability first increased and then decreased as τ increased, showing an optimal TRT method emerging the best numerical stability. The free selection of τ enabled the TRT LBM to simulate the Gaussian hill transport and Taylor dispersion under relatively high advective velocity, under which the SRT LBM suffered from numerical instability. Finally, the TRT method was applied to study the contaminant degradation by chemotactic microorganisms in porous media, which acted as a reprehensive of reactive transport in this study, and well predicted the evolution of microorganisms and degradation of contaminants for different transport scenarios. To sum up, the TRT LBM produced simulation results with good accuracy and stability for various advective-diffusive-reactive transport through tuning the relaxation

Nuclear magnetic relaxation by the dipolar EMOR mechanism: Multi-spin systems

NASA Astrophysics Data System (ADS)

Chang, Zhiwei; Halle, Bertil

2017-08-01

In aqueous systems with immobilized macromolecules, including biological tissues, the longitudinal spin relaxation of water protons is primarily induced by exchange-mediated orientational randomization (EMOR) of intra- and intermolecular magnetic dipole-dipole couplings. Starting from the stochastic Liouville equation, we have previously developed a rigorous EMOR relaxation theory for dipole-coupled two-spin and three-spin systems. Here, we extend the stochastic Liouville theory to four-spin systems and use these exact results as a guide for constructing an approximate multi-spin theory, valid for spin systems of arbitrary size. This so-called generalized stochastic Redfield equation (GSRE) theory includes the effects of longitudinal-transverse cross-mode relaxation, which gives rise to an inverted step in the relaxation dispersion profile, and coherent spin mode transfer among solid-like spins, which may be regarded as generalized spin diffusion. The GSRE theory is compared to an existing theory, based on the extended Solomon equations, which does not incorporate these phenomena. Relaxation dispersion profiles are computed from the GSRE theory for systems of up to 16 protons, taken from protein crystal structures. These profiles span the range from the motional narrowing limit, where the coherent mode transfer plays a major role, to the ultra-slow motion limit, where the zero-field rate is closely related to the strong-collision limit of the dipolar relaxation rate. Although a quantitative analysis of experimental data is beyond the scope of this work, it is clear from the magnitude of the predicted relaxation rate and the shape of the relaxation dispersion profile that the dipolar EMOR mechanism is the principal cause of water-1H low-field longitudinal relaxation in aqueous systems of immobilized macromolecules, including soft biological tissues. The relaxation theory developed here therefore provides a basis for molecular-level interpretation of endogenous soft

Slowed Relaxation in Fatigued Skeletal Muscle Fibers of Xenopus and Mouse

PubMed Central

Westerblad, Håkan; Lännergren, Jan; Allen, David G.

1997-01-01

Slowing of relaxation is an important characteristic of skeletal muscle fatigue. The aim of the present study was to quantify the relative contribution of altered Ca2+ handling (calcium component) and factors down-stream to Ca2+ (cross-bridge component) to the slowing of relaxation in fatigued fibers of Xenopus and mouse. Two types of Xenopus fibers were used: easily fatigued, type 1 fibers and fatigue resistant, type 2 fibers. In these Xenopus fibers the free myoplasmic [Ca2+] ([Ca2+]i) was measured with indo-1, and the relaxation of Ca2+-derived force, constructed from tetanic [Ca2+]i records and in vivo [Ca2+]i-force curves, was analyzed. An alternative method was used in both Xenopus and mouse fibers: fibers were rapidly shortened during the initial phase of relaxation, and the time to the peak of force redevelopment was measured. These two methods gave similar results and showed proportional slowing of the calcium and cross-bridge components of relaxation in both fatigued type 1 and type 2 Xenopus fibers, whereas only the cross-bridge component was slowed in fatigued mouse fibers. Ca2+ removal from the myoplasm during relaxation was markedly less effective in Xenopus fibers as compared to mouse fibers. Fatigued Xenopus fibers displayed a reduced rate of sarcoplasmic reticulum Ca2+ uptake and increased sarcoplasmic reticulum Ca2+ leak. Some fibers were stretched at various times during relaxation. The resistance to these stretches was increased during fatigue, especially in Xenopus fibers, which indicates that longitudinal movements during relaxation had become less pronounced and this might contribute to the increased cross-bridge component of relaxation in fatigue. In conclusion, slowing of relaxation in fatigued Xenopus fibers is caused by impaired Ca2+ handling and altered cross-bridge kinetics, whereas the slowing in mouse fibers is only due to altered cross-bridge kinetics. PMID:9089444

Prospective study of blood metabolites associated with colorectal cancer risk.

PubMed

Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

2018-02-26

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

PubMed Central

Wood, JodiAnne T.; Williams, John S.; Pandarinathan, Lakshmipathi; Janero, David R.; Lammi-Keefe, Carol J.; Makriyannis, Alexandros

2010-01-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications. PMID:20071693

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma.

PubMed

Wood, Jodianne T; Williams, John S; Pandarinathan, Lakshmipathi; Janero, David R; Lammi-Keefe, Carol J; Makriyannis, Alexandros

2010-06-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications.

Studying relaxation phenomena via effective master equations

NASA Astrophysics Data System (ADS)

Chan, David; Wan, Jones T. K.; Chu, L. L.; Yu, K. W.

2000-04-01

The real-time dynamics of various relaxation phenomena can be conveniently formulated by a master equation with the enumeration of transition rates between given classes of conformations. To study the relaxation time towards equilibrium, it suffices to solve for the second largest eigenvalue of the resulting eigenvalue equation. Generally speaking, there is no analytic solution for the dynamic equation. Mean-field approaches generally yield misleading results while the presumably exact Monte-Carlo methods require prohibitive time steps in most real systems. In this work, we propose an exact decimation procedure for reducing the number of conformations significantly, while there is no loss of information, i.e., the reduced (or effective) equation is an exact transformed version of the original one. However, we have to pay the price: the initial Markovianity of the evolution equation is lost and the reduced equation contains memory terms in the transition rates. Since the transformed equation has significantly reduced number of degrees of freedom, the systems can readily be diagonalized by iterative means, to obtain the exact second largest eigenvalue and hence the relaxation time. The decimation method has been applied to various relaxation equations with generally desirable results. The advantages and limitations of the method will be discussed.

Charge Relaxation Dynamics of an Electrolytic Nanocapacitor

PubMed Central

2015-01-01

Understanding ion relaxation dynamics in overlapping electric double layers (EDLs) is critical for the development of efficient nanotechnology-based electrochemical energy storage, electrochemomechanical energy conversion, and bioelectrochemical sensing devices as well as the controlled synthesis of nanostructured materials. Here, a lattice Boltzmann (LB) method is employed to simulate an electrolytic nanocapacitor subjected to a step potential at t = 0 for various degrees of EDL overlap, solvent viscosities, ratios of cation-to-anion diffusivity, and electrode separations. The use of a novel continuously varying and Galilean-invariant molecular-speed-dependent relaxation time (MSDRT) with the LB equation recovers a correct microscopic description of the molecular-collision phenomena and enhances the stability of the LB algorithm. Results for large EDL overlaps indicated oscillatory behavior for the ionic current density, in contrast to monotonic relaxation to equilibrium for low EDL overlaps. Further, at low solvent viscosities and large EDL overlaps, anomalous plasmalike spatial oscillations of the electric field were observed that appeared to be purely an effect of nanoscale confinement. Employing MSDRT in our simulations enabled modeling of the fundamental physics of the transient charge relaxation dynamics in electrochemical systems operating away from equilibrium wherein Nernst–Einstein relation is known to be violated. PMID:25678941

Tension and relaxation in the individual.

PubMed

Newbury, C R

1979-06-01

Increasing materialism in society is resulting in more wide spread nervous tension in all age groups. While some degree of nervous tension is necessary in everyday living, its adverse effects require that we must learn to bring it under control. Total tension is shown to have two components: a controllable element arising from factors in the environment and the inbuilt uncontrollable residue which is basic in the individual temperament. The effects of excessive or uncontrolled stress can be classified as 1) emotional reactions such as neurotic behaviour (anxiety hypochondria, hysteria, phobia, depression obsessions and compulsions) or psychotic behaviour and 2) psychosomatic reactions (nervous asthma, headache, insomnia, heart attack). Nervous energy can be wastefully expended by such factors as loss of temper, wrong attitudes to work, job frustration and marital strains. Relaxation is the only positive way to control undesirable nervous tension and its techniques require to be learned. A number of techniques (progressive relaxation, differential relaxation, hypnosis, the use of biofeedback, Yoga and Transcendental Meditation) are described and their application to dental practice is discussed.

Relaxation dynamics of internal segments of DNA chains in nanochannels

NASA Astrophysics Data System (ADS)

Jain, Aashish; Muralidhar, Abhiram; Dorfman, Kevin; Dorfman Group Team

We will present relaxation dynamics of internal segments of a DNA chain confined in nanochannel. The results have direct application in genome mapping technology, where long DNA molecules containing sequence-specific fluorescent probes are passed through an array of nanochannels to linearize them, and then the distances between these probes (the so-called ``DNA barcode'') are measured. The relaxation dynamics of internal segments set the experimental error due to dynamic fluctuations. We developed a multi-scale simulation algorithm, combining a Pruned-Enriched Rosenbluth Method (PERM) simulation of a discrete wormlike chain model with hard spheres with Brownian dynamics (BD) simulations of a bead-spring chain. Realistic parameters such as the bead friction coefficient and spring force law parameters are obtained from PERM simulations and then mapped onto the bead-spring model. The BD simulations are carried out to obtain the extension autocorrelation functions of various segments, which furnish their relaxation times. Interestingly, we find that (i) corner segments relax faster than the center segments and (ii) relaxation times of corner segments do not depend on the contour length of DNA chain, whereas the relaxation times of center segments increase linearly with DNA chain size.

A fast determination method for transverse relaxation of spin-exchange-relaxation-free magnetometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Jixi, E-mail: lujixi@buaa.edu.cn; Qian, Zheng; Fang, Jiancheng

2015-04-15

We propose a fast and accurate determination method for transverse relaxation of the spin-exchange-relaxation-free (SERF) magnetometer. This method is based on the measurement of magnetic resonance linewidth via a chirped magnetic field excitation and the amplitude spectrum analysis. Compared with the frequency sweeping via separate sinusoidal excitation, our method can realize linewidth determination within only few seconds and meanwhile obtain good frequency resolution. Therefore, it can avoid the drift error in long term measurement and improve the accuracy of the determination. As the magnetic resonance frequency of the SERF magnetometer is very low, we include the effect of the negativemore » resonance frequency caused by the chirp and achieve the coefficient of determination of the fitting results better than 0.998 with 95% confidence bounds to the theoretical equation. The experimental results are in good agreement with our theoretical analysis.« less

Phospholemman does not participate in forskolin-induced swine carotid artery relaxation.

PubMed

Meeks, M K; Han, S; Tucker, A L; Rembold, C M

2008-01-01

Phosphorylation of phospholemman (PLM) on ser68 has been proposed to at least partially mediate cyclic AMP (cAMP) mediated relaxation of arterial smooth muscle. We evaluated the time course of the phosphorylation of phospholemman (PLM) on ser68, myosin regulatory light chains (MRLC) on ser19, and heat shock protein 20 (HSP20) on ser16 during a transient forskolin-induced relaxation of histamine-stimulated swine carotid artery. We also evaluated the dose response for forskolin- and nitroglycerin-induced relaxation in phenylephrine-stimulated PLM-/- and PLM+/+ mice. The time course for changes in ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation was appropriate to explain the forskolin-induced relaxation and the recontraction observed upon washout of forskolin. However, the time course for changes in ser68 PLM phosphorylation was too slow to explain forskolin-induced changes in force. There was no difference in the phenylephrine contractile dose response or in forskolin-induced relaxation dose response observed in PLM-/- and PLM+/+ aortae. In aortae precontracted with phenylephrine, nitroglycerin induced a slightly, but significantly greater relaxation in PLM-/- compared to PLM+/+ aortae. These data are consistent with the hypothesis that ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation are involved in forskolin-induced relaxation. Our data suggest that PLM phosphorylation is not significantly involved in forskolin-induced arterial relaxation.

Alpha 2-adrenoceptors and endothelium-dependent relaxation in canine large arteries.

PubMed Central

Angus, J. A.; Cocks, T. M.; Satoh, K.

1986-01-01

Ring preparations from the carotid, coronary, renal, mesenteric and femoral arteries of the dog were precontracted with the thromboxane mimetic U46619, after ensuring that the resting conditions were comparable from the Laplace relationship. In the presence of prazosin (1 microM) and propranolol (3 microM), noradrenaline (NA) relaxed the arteries in the order coronary greater than carotid greater than femoral greater than renal = mesenteric. When maximum relaxation to nitroglycerin (10 microM) was taken to be 100% the maximum relaxation to noradrenaline in each artery was: coronary 70%; carotid 34%; femoral 19%; renal 7% and mesenteric 2%. In endothelium-intact arteries UK14304 mimicked the relaxation responses to NA and idazoxan shifted the curves to both agonists to the right, consistent with an alpha 2-adrenoceptor classification. Substance P relaxed the arteries in the same order as for NA but showed higher efficacy i.e.: coronary 100%; carotid 80%; femoral 71% renal 49%; and mesenteric 41%. Removal of the endothelium abolished the relaxation to NA. We conclude that endothelium-dependent relaxation to NA and substance P varies greatly across 5 large arteries of the dog. This may indicate that endothelium-derived relaxing factor (EDRF) release is site-dependent or that the efficacy of EDRF on smooth muscle varies; being greatest in the coronary and weakest in the renal and mesenteric arteries. PMID:2427147

A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

PubMed

Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

2013-05-01

Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

Local moment relaxation in heavy-fermion compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simanek, E.; Sasahara, K.

1987-02-01

The Korringa relaxation rate for a local moment of an impurity in a heavy fermion compound is calculated using the model of Yoshimori and Kasai. Consistent with the recent ESR data for local moments in UBe/sub 13/, the relaxation rate is found to be unaffected by the heavy fermion renormalizations. This result can be traced to the single-site approximation and the weak k dependence of the conduction electron self-energy.

Pharmacogenetic determinants of mercaptopurine disposition in children with acute lymphoblastic leukemia.

PubMed

Adam de Beaumais, Tiphaine; Jacqz-Aigrain, Evelyne

2012-09-01

The backbone of drug therapy used in acute lymphoblastic leukemia (ALL) in children includes 6-mercaptopurine (6-MP). Intracellular metabolism of this prodrug is a key component of the therapeutic response. Many metabolizing enzymes are involved in 6-MP disposition and active 6-MP metabolites are represented by 6-thioguanine nucleotides (6-TGN) and methylated metabolites primarily methylated by the thiopurine S-methyltransferase enzyme (TPMT). The genetic polymorphism affecting TPMT activity displays an important inter-subject variability in metabolites pharmacokinetics and influences the balance between 6-MP efficacy and toxicity: patients with high 6-TGN levels are at risk of myelosuppression while patients with high levels of methylated derivates are at hepatotoxic risk. However, the genetic TPMT polymorphism does not explain all 6-MP adverse events and some severe toxicities leading to life-threatening conditions remain unexplained. Additional single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in 6-MP metabolism and 6-MP transporters may also be responsible for this inter-individual 6-MP response variability. This review presents the pharmacogenetic aspects of 6-MP metabolism in great detail. We have focused on published data on ALL treatment supporting the great potential of 6-MP pharmacogenetics to improve efficacy, tolerance, and event-free survival rates in children with ALL.

Generalized extended Navier-Stokes theory: multiscale spin relaxation in molecular fluids.

PubMed

Hansen, J S

2013-09-01

This paper studies the relaxation of the molecular spin angular velocity in the framework of generalized extended Navier-Stokes theory. Using molecular dynamics simulations, it is shown that for uncharged diatomic molecules the relaxation time decreases with increasing molecular moment of inertia per unit mass. In the regime of large moment of inertia the fast relaxation is wave-vector independent and dominated by the coupling between spin and the fluid streaming velocity, whereas for small inertia the relaxation is slow and spin diffusion plays a significant role. The fast wave-vector-independent relaxation is also observed for highly packed systems. The transverse and longitudinal spin modes have, to a good approximation, identical relaxation, indicating that the longitudinal and transverse spin viscosities have same value. The relaxation is also shown to be isomorphic invariant. Finally, the effect of the coupling in the zero frequency and wave-vector limit is quantified by a characteristic length scale; if the system dimension is comparable to this length the coupling must be included into the fluid dynamical description. It is found that the length scale is independent of moment of inertia but dependent on the state point.

Trichoderma secondary metabolites that affect plant metabolism.

PubMed

Vinale, Francesco; Sivasithamparam, Krishnapillai; Ghisalberti, Emilio L; Ruocco, Michelina; Wood, Sheridan; Lorito, Matteo

2012-11-01

Recently, there have been many exciting new developments relating to the use of Trichoderma spp. as agents for biocontrol of pathogens and as plant growth promoters. Several mechanisms have been proposed to explain the positive effects of these microorganisms on the plant host. One factor that contributes to their beneficial biological activities is related to the wide variety of metabolites that they produce. These metabolites have been found not only to directly inhibit the growth and pathogenic activities of the parasites, but also to increase disease resistance by triggering the system of defence in the plant host. In addition, these metabolites are also capable of enhancing plant growth, which enables the plant to counteract the disease with compensatory vegetative growth by the augmented production of root and shoot systems. This review takes into account the Trichoderma secondary metabolites that affect plant metabolism and that may play an important role in the complex interactions of this biocontrol agent with the plant and pathogens.

S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

PubMed Central

Matsumoto, Kensuke; Kitanaka, Akira; Uemura, Makiko; Waki, Fusako; Fukumoto, Tetsuya; Ohnishi, Hiroaki; Kubota, Yoshitsugu; Ishida, Toshihiko

2011-01-01

Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration, and that hematological adverse events were relatively rare. Pyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-II inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia. PMID:22147971

[Specifics of bio-controlled training in directed relaxation].

PubMed

Baranov, V M; Sentiabrev, N N; Solopov, I N

2005-01-01

Studies of personal and general patterns of acquisition of skills in biocontrolled relaxation based on biological feedback (EMG) permitted classification of human subjects by the ability to relax voluntarily muscles. In the process of skill acquisition changes were minimal at the beginning, grew progressively further on and stabilized on completion of the course of training.

Metabolite identification through multiple kernel learning on fragmentation trees.

PubMed

Shen, Huibin; Dührkop, Kai; Böcker, Sebastian; Rousu, Juho

2014-06-15

Metabolite identification from tandem mass spectrometric data is a key task in metabolomics. Various computational methods have been proposed for the identification of metabolites from tandem mass spectra. Fragmentation tree methods explore the space of possible ways in which the metabolite can fragment, and base the metabolite identification on scoring of these fragmentation trees. Machine learning methods have been used to map mass spectra to molecular fingerprints; predicted fingerprints, in turn, can be used to score candidate molecular structures. Here, we combine fragmentation tree computations with kernel-based machine learning to predict molecular fingerprints and identify molecular structures. We introduce a family of kernels capturing the similarity of fragmentation trees, and combine these kernels using recently proposed multiple kernel learning approaches. Experiments on two large reference datasets show that the new methods significantly improve molecular fingerprint prediction accuracy. These improvements result in better metabolite identification, doubling the number of metabolites ranked at the top position of the candidates list. © The Author 2014. Published by Oxford University Press.

Heteronuclear transverse and longitudinal relaxation in AX4 spin systems: Application to 15N relaxations in 15NH4+

PubMed Central

Werbeck, Nicolas D.; Hansen, D. Flemming

2014-01-01

The equations that describe the time-evolution of transverse and longitudinal 15N magnetisations in tetrahedral ammonium ions, 15NH4+, are derived from the Bloch-Wangsness-Redfield density operator relaxation theory. It is assumed that the relaxation of the spin-states is dominated by (1) the intra-molecular 15N–1H and 1H–1H dipole–dipole interactions and (2) interactions of the ammonium protons with remote spins, which also include the contribution to the relaxations that arise from the exchange of the ammonium protons with the bulk solvent. The dipole–dipole cross-correlated relaxation mechanisms between each of the 15N–1H and 1H–1H interactions are explicitly taken into account in the derivations. An application to 15N-ammonium bound to a 41 kDa domain of the protein DnaK is presented, where a comparison between experiments and simulations show that the ammonium ion rotates rapidly within its binding site with a local correlation time shorter than approximately 1 ns. The theoretical framework provided here forms the basis for further investigations of dynamics of AX4 spin systems, with ammonium ions in solution and bound to proteins of particular interest. PMID:25128779

Biexciton relaxation associated with dissociation into a surface polariton pair in semiconductor films

NASA Astrophysics Data System (ADS)

Mitsumori, Yasuyoshi; Matsuura, Shimpei; Uchiyama, Shoichi; Saito, Kentarao; Edamatsu, Keiichi; Nakayama, Masaaki; Ajiki, Hiroshi

2018-04-01

We study the biexciton relaxation process in CuCl films ranging from 6 to 200 nm. The relaxation time is measured as the dephasing time and the lifetime. We observe a unique thickness dependence of the biexciton relaxation time and also obtain an ultrafast relaxation time with a timescale as short as 100 fs, while the exciton lifetime monotonically decreases with increasing thickness. By analyzing the exciton-photon coupling energy for a surface polariton, we theoretically calculate the biexciton relaxation time as a function of the thickness. The calculated dependence qualitatively reproduces the observed relaxation time, indicating that the biexciton dissociation into a surface polariton pair is one of the major biexciton relaxation processes.

[Autism and Autism-associated Metabolites].

PubMed

Watanabe, Kunitomo

2016-06-01

Gene-microbiota interactions are now proposed to be a special case of gene-environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors.

Relaxed impact craters on Ganymede: Regional variation and high heat flows

NASA Astrophysics Data System (ADS)

Singer, Kelsi N.; Bland, Michael T.; Schenk, Paul M.; McKinnon, William B.

2018-05-01

Viscously relaxed craters provide a window into the thermal history of Ganymede, a satellite with copious geologic signs of past high heat flows. Here we present measurements of relaxed craters in four regions for which suitable imaging exists: near Anshar Sulcus, Tiamat Sulcus, northern Marius Regio, and Ganymede's south pole. We describe a technique to measure apparent depth, or depth of the crater with respect to the surrounding terrain elevation. Measured relaxation states are compared with results from finite element modeling to constrain heat flow scenarios [see companion paper: Bland et al. (2017)]. The presence of numerous, substantially relaxed craters indicates high heat flows-in excess of 30-40 mW m-2 over 2 Gyr, with many small (<10 km in diameter) relaxed craters indicating even higher heat flows. Crater relaxation states are bimodal for some equatorial regions but not in the region studied near the south pole, which suggests regional variations in Ganymede's thermal history.

Hydrogels with tunable stress relaxation regulate stem cell fate and activity

NASA Astrophysics Data System (ADS)

Chaudhuri, Ovijit; Gu, Luo; Klumpers, Darinka; Darnell, Max; Bencherif, Sidi A.; Weaver, James C.; Huebsch, Nathaniel; Lee, Hong-Pyo; Lippens, Evi; Duda, Georg N.; Mooney, David J.

2016-03-01

Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel's initial elastic modulus, degradation, and cell-adhesion-ligand density. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.

Introductory Chemistry: A Molar Relaxivity Experiment in the High School Classroom.

PubMed

Dawsey, Anna C; Hathaway, Kathryn L; Kim, Susie; Williams, Travis J

2013-07-09

Dotarem and Magnevist, two clinically available magnetic resonance imaging (MRI) contrast agents, were assessed in a high school science classroom with respect to which is the better contrast agent. Magnevist, the more efficacious contrast agent, has negative side effects because its gadolinium center can escape from its ligand. However, Dotarem, though a less efficacious contrast agent, is a safer drug choice. After the experiment, students are confronted with the FDA warning on Magnevist, which enabled a discussion of drug efficacy versus safety. We describe a laboratory experiment in which NMR spin lattice relaxation rate measurements are used to quantify the relaxivities of the active ingredients of Dotarem and Magnevist. The spin lattice relaxation rate gives the average amount of time it takes the excited nucleus to relax back to the original state. Students learn by constructing molar relaxivity curves based on inversion recovery data sets that Magnevist is more relaxive than Dotarem. This experiment is suitable for any analytical chemistry laboratory with access to NMR.

Multi-Phonon Relaxation of H^- Local Modes in CaF_2

NASA Astrophysics Data System (ADS)

Davison, C. P.; Happek, U.; Campbell, J. A.; Engholm, J. R.; Schwettman, H. A.

1998-03-01

Local modes play an important role in the relaxation of vibrational modes of small molecules in solids (J.R. Engholm, C.W. Rella, H.A. Schwettman, and U. Happek; Phys. Rev. Lett. 77), 1302 (1996)., but only few attempts have been reported to study the relaxation of these local modes. Here we report on experiments to investigate the non-radiative relaxation of H^- local modes in CaF_2. Using a pump-probe technique, saturation experiments on the H^- local modes, both interstitial and substitutional, were performed at the Stanford Free Electron Laser Center. At low temperature we find a relaxation time T1 of 45 psec for the substitutional H^- local mode, and a more rapid relaxation for the interstitial H^- local modes next to La^3+ and Lu^3+ impurities. Information on the decay channels of the local modes are obtained from the characteristic temperature dependence of the relaxation rates. This work is supported in part by the ONR, Grant No. N00014-94-1024.

Relaxed impact craters on Ganymede: Regional variation and high heat flows

USGS Publications Warehouse

Singer, Kelsi N.; Bland, Michael T.; Schenk, Paul M.; McKinnon, William B.

2018-01-01

Viscously relaxed craters provide a window into the thermal history of Ganymede, a satellite with copious geologic signs of past high heat flows. Here we present measurements of relaxed craters in four regions for which suitable imaging exists: near Anshar Sulcus, Tiamat Sulcus, northern Marius Regio, and Ganymede's south pole. We describe a technique to measure apparent depth, or depth of the crater with respect to the surrounding terrain elevation. Measured relaxation states are compared with results from finite element modeling to constrain heat flow scenarios [see companion paper: Bland et al. (2017)]. The presence of numerous, substantially relaxed craters indicates high heat flows—in excess of 30–40 mW m−2 over 2 Gyr, with many small (<10 km in diameter) relaxed craters indicating even higher heat flows. Crater relaxation states are bimodal for some equatorial regions but not in the region studied near the south pole, which suggests regional variations in Ganymede's thermal history.

Hydrogels with tunable stress relaxation regulate stem cell fate and activity

PubMed Central

Chaudhuri, Ovijit; Gu, Luo; Klumpers, Darinka; Darnell, Max; Bencherif, Sidi A.; Weaver, James C.; Huebsch, Nathaniel; Lee, Hong-pyo; Lippens, Evi; Duda, Georg N.; Mooney, David J.

2015-01-01

Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel’s initial elastic modulus, cell-adhesion-ligand density and degradation. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture. PMID:26618884

Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

PubMed Central

Lever, Michael; George, Peter M.; Elmslie, Jane L.; Atkinson, Wendy; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

2012-01-01

Background Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. Methods Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. Principal Findings The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). Conclusions Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk. PMID:22649561

Increasing mathematical problem-solving performance through relaxation training

NASA Astrophysics Data System (ADS)

Sharp, Conni; Coltharp, Hazel; Hurford, David; Cole, Amykay

2000-04-01

Two intact classes of 30 undergraduate students enrolled in the same general education mathematics course were each administered the IPSP Mathematics Problem Solving Test and the Mathematics Anxiety Rating Scale at the beginning and end of the semester. Both groups experienced the same syllabus, lectures, course requirements, and assessment techniques; however, one group received relaxation training during an initial class meeting and during the first 5 to 7 minutes of each subsequent class. The group which had received relaxation training had significantly lower mathematics anxiety and significantly higher mathematics performance at the end of the course. The results suggest that relaxation training may be a useful tool for treating anxiety in undergraduate general education mathematics students.

Metabolic control analysis using transient metabolite concentrations. Determination of metabolite concentration control coefficients.

PubMed Central

Delgado, J; Liao, J C

1992-01-01

The methodology previously developed for determining the Flux Control Coefficients [Delgado & Liao (1992) Biochem. J. 282, 919-927] is extended to the calculation of metabolite Concentration Control Coefficients. It is shown that the transient metabolite concentrations are related by a few algebraic equations, attributed to mass balance, stoichiometric constraints, quasi-equilibrium or quasi-steady states, and kinetic regulations. The coefficients in these relations can be estimated using linear regression, and can be used to calculate the Control Coefficients. The theoretical basis and two examples are discussed. Although the methodology is derived based on the linear approximation of enzyme kinetics, it yields reasonably good estimates of the Control Coefficients for systems with non-linear kinetics. PMID:1497632

The Robustness of Cluster Expansion: Assessing the Role of Relaxation

NASA Astrophysics Data System (ADS)

Nguyen, Andrew H.; Rosenbrock, Conrad W.; Hart, Gus L. W.

Cluster expansion (CE) has been used widely in combination with first-principles calculations to predict stable structures of metal alloys. CE treats alloys as a purely configuration problem, i.e., a problem in the distribution of the alloying elements on a fixed lattice. CE models are usually built from data taken from ``relaxed'' first-principles calculations where the individual atoms assume positions that minimize the total energy. A perennial question in the cluster expansion community is how the accuracy of the CE is affected by relaxations--technically, the formalism of CE breaks down when the underlying lattice is not preserved--but practitioners often argue that there is a one-to-one correspondence between relaxed and unrelaxed structures so that the formalism holds. We quantify the effect of relaxation on the robustness of cluster expansions by comparing CE fits for relaxed and unrelaxed data sets. Our results give a heuristic for when CE models can be trusted. Onr (MURI N00014-13-1-0635).