Science.gov

Sample records for agonist dissociation constants

  1. Dissociation rate constant of the biotin-streptavidin complex.

    PubMed

    Piran, U; Riordan, W J

    1990-10-01

    We measured the dissociation rate constants of the biotin/streptavidin and biotin/egg avidin complexes by following the release of radiolabeled biotin from the preformed complexes in the presence of excess unlabeled biotin. For separation of bound and free labeled biotin we employed ultrafiltration with disposable microconcentrators. The dissociation rate constant for underivatized streptavidin was 2.4 x 10(-6) s-1, or approximately 30-fold higher than that observed for egg avidin 7.5 x 10(-8) s-1). The value for streptavidin was further increased after derivatization with an acridinium ester label. Both biotin binding proteins exhibited a faster initial phase, suggesting binding site heterogeneity due to partial subunit dissociation or denaturation. The convenience of the method and the relatively fast dissociation of biotin from streptavidin render the dissociation rate constant a practical experimental criterion for monitoring the integrity of the binding site during purification and derivatization procedures. PMID:2212686

  2. Semiclassical Calculation of Reaction Rate Constants for Homolytical Dissociations

    NASA Technical Reports Server (NTRS)

    Cardelino, Beatriz H.

    2002-01-01

    There is growing interest in extending organometallic chemical vapor deposition (OMCVD) to III-V materials that exhibit large thermal decomposition at their optimum growth temperature, such as indium nitride. The group III nitrides are candidate materials for light-emitting diodes and semiconductor lasers operating into the blue and ultraviolet regions. To overcome decomposition of the deposited compound, the reaction must be conducted at high pressures, which causes problems of uniformity. Microgravity may provide the venue for maintaining conditions of laminar flow under high pressure. Since the selection of optimized parameters becomes crucial when performing experiments in microgravity, efforts are presently geared to the development of computational OMCVD models that will couple the reactor fluid dynamics with its chemical kinetics. In the present study, we developed a method to calculate reaction rate constants for the homolytic dissociation of III-V compounds for modeling OMCVD. The method is validated by comparing calculations with experimental reaction rate constants.

  3. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    PubMed

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  4. Dissociation constants of phosphoric acid in dimethylformamide-water mixtures at 298.15 K

    NASA Astrophysics Data System (ADS)

    Safonova, L. P.; Fadeeva, Yu. A.; Pryakhin, A. A.

    2009-10-01

    The dissociation constants of phosphoric acid (p K 1 and p K 2) in water-dimethylformamide (DMFA) mixtures (0-0.65 mole fractions of DMFA) were determined at 298.15 K by potentiometric titration. The extrapolation of these data to pure DMFA and the comparative calculation method were used to estimate the dissociation constants of the acid in DMFA.

  5. Simulations of dissociation constants in low pressure supercritical water

    NASA Astrophysics Data System (ADS)

    Halstead, S. J.; An, P.; Zhang, S.

    2014-09-01

    This article reports molecular dynamics simulations of the dissociation of hydrochloric acid and sodium hydroxide in water from ambient to supercritical temperatures at a fixed pressure of 250 atm. Corrosion of reaction vessels is known to be a serious problem of supercritical water, and acid/base dissociation can be a significant contributing factor to this. The SPC/e model was used in conjunction with solute models determined from density functional calculations and OPLSAA Lennard-Jones parameters. Radial distribution functions were calculated, and these show a significant increase in solute-solvent ordering upon forming the product ions at all temperatures. For both dissociations, rapidly decreasing entropy of reaction was found to be the controlling thermodynamic factor, and this is thought to arise due to the ions produced from dissociation maintaining a relatively high density and ordered solvation shell compared to the reactants. The change in entropy of reaction reaches a minimum at the critical temperature. The values of pKa and pKb were calculated and both increased with temperature, in qualitative agreement with other work, until a maximum value at 748 K, after which there was a slight decrease.

  6. High Throughput pharmacokinetic modeling using computationally predicted parameter values: dissociation constants (TDS)

    EPA Science Inventory

    Estimates of the ionization association and dissociation constant (pKa) are vital to modeling the pharmacokinetic behavior of chemicals in vivo. Methodologies for the prediction of compound sequestration in specific tissues using partition coefficients require a parameter that ch...

  7. Inhibition of ionotropic neurotransmitter receptors by antagonists: strategy to estimate the association and the dissociation rate constant of antagonists with very strong affinity to the receptors.

    PubMed

    Aoshima, H; Inoue, Y; Hori, K

    1992-10-01

    Since binding of an agonist to an ionotropic neurotransmitter receptor causes not only channel opening, but also desensitization of the receptor, inhibition of the receptor by the antagonist sometimes becomes very complicated. The transient state kinetics of ligand association and dissociation, and desensitization of the receptor were considered on the basis of the minimal model proposed by Hess' group, and the following possibilities were proposed. 1) When an agonist is simultaneously applied to the receptor with an antagonist whose affinity to the receptor is extremely strong and different from that of the agonist, it is usually impossible to estimate the real inhibition constant exactly from the responses because desensitization of the receptor proceeds before the equilibrium of the ligand binding. Simultaneous addition of the antagonist with strong affinity to the receptor may apparently accelerate inactivation (desensitization) of the receptor. The association rate constant of the antagonist can be estimated by analyses of the rate of the inactivation in the presence and the absence of the antagonist. 2) A preincubated antagonist with a slow dissociation rate constant, i.e., a very effective inhibitor, may cause apparent noncompetitive inhibition of the receptor, since the receptor is desensitized by an agonist as soon as the antagonist dissociates from the receptor and the dissociation of the antagonist from the receptor becomes the rate-determining step. A nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus oocytes by injecting mRNA prepared from Electrophorus electricus electroplax and used for the experiments on inhibition by an antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1337082

  8. Determination of dissociation constants of cytokinins by capillary zone electrophoresis.

    PubMed

    Barták, P; Bednár, P; Stránský, Z; Bocek, P; Vespalec, R

    2000-05-12

    A method for the pKa determination, based on mobility data measured by capillary zone electrophoresis, was applied to cytokinins and their analogs. The combination of charged mobility standards with an uncharged electroosmosis marker, injected in the uncoated capillary simultaneously with the measured substances, allows one to minimize the number of runs, reduce their duration and, in addition, to inform on the run-to-run stability of electroosmosis and on contingent side-effects. pKa values of investigated cytokinins and their analogs ranged from 2.8 to 4.0 at 25 degrees C in the phosphate and acetate buffers of ionic strength 0.015 M. Standard deviations of the constants, obtained by the non-linear fitting of equations for the pKa calculation, were 3-5-times lower than standard deviations from the linear fitting or from the point-to-point calculation utilizing the Hendersson-Haselbalch equation. The equation of Boltzman sigmoid offers two checks on reliability of effective mobilities that serve as the raw data in the pKa calculation. PMID:10866070

  9. The vibrational dependence of dissociative recombination: Rate constants for N{sub 2}{sup +}

    SciTech Connect

    Guberman, Steven L.

    2014-11-28

    Dissociative recombination rate constants are reported with electron temperature dependent uncertainties for the lowest 5 vibrational levels of the N{sub 2}{sup +} ground state. The rate constants are determined from ab initio calculations of potential curves, electronic widths, quantum defects, and cross sections. At 100 K electron temperature, the rate constants overlap with the exception of the third vibrational level. At and above 300 K, the rate constants for excited vibrational levels are significantly smaller than that for the ground level. It is shown that any experimentally determined total rate constant at 300 K electron temperature that is smaller than 2.0 × 10{sup −7} cm{sup 3}/s is likely to be for ions that have a substantially excited vibrational population. Using the vibrational level specific rate constants, the total rate constant is in very good agreement with that for an excited vibrational distribution found in a storage ring experiment. It is also shown that a prior analysis of a laser induced fluorescence experiment is quantitatively flawed due to the need to account for reactions with unknown rate constants. Two prior calculations of the dissociative recombination rate constant are shown to be inconsistent with the cross sections upon which they are based. The rate constants calculated here contribute to the resolution of a 30 year old disagreement between modeled and observed N{sub 2}{sup +} ionospheric densities.

  10. DISSOCIATION OF ARSENITE-PEPTIDE COMPLEXES: TRIPHASIC NATURE, RATE CONSTANTS, HALF LIVES AND BIOLOGICAL IMPORTANCE

    EPA Science Inventory

    We determined the number and the dissociation rate constants of different complexes formed from arsenite and two peptides containing either one (RV AVGNDYASGYHYGV for peptide 20) or three cysteines (LE AWQGK VEGTEHLYSMK K for peptide 10) via radioactive 73As labeled arsenite and ...

  11. A Unified Kinetics and Equilibrium Experiment: Rate Law, Activation Energy, and Equilibrium Constant for the Dissociation of Ferroin

    ERIC Educational Resources Information Center

    Sattar, Simeen

    2011-01-01

    Tris(1,10-phenanthroline)iron(II) is the basis of a suite of four experiments spanning 5 weeks. Students determine the rate law, activation energy, and equilibrium constant for the dissociation of the complex ion in acid solution and base dissociation constant for phenanthroline. The focus on one chemical system simplifies a daunting set of…

  12. Determination of Henry's constant, the dissociation constant, and the buffer capacity of the bicarbonate system in ruminal fluid.

    PubMed

    Hille, Katharina T; Hetz, Stefan K; Rosendahl, Julia; Braun, Hannah-Sophie; Pieper, Robert; Stumpff, Friederike

    2016-01-01

    Despite the clinical importance of ruminal acidosis, ruminal buffering continues to be poorly understood. In particular, the constants for the dissociation of H2CO3 and the solubility of CO2 (Henry's constant) have never been stringently determined for ruminal fluid. The pH was measured in parallel directly in the rumen and the reticulum in vivo, and in samples obtained via aspiration from 10 fistulated cows on hay- or concentrate-based diets. The equilibrium constants of the bicarbonate system were measured at 38°C both using the Astrup technique and a newly developed method with titration at 2 levels of partial pressure of CO2 (pCO2; 4.75 and 94.98 kPa), yielding mean values of 0.234 ± 0.005 mmol ∙ L(-1) ∙ kPa(-1) and 6.11 ± 0.02 for Henry's constant and the dissociation constant, respectively (n/n = 31/10). Both reticular pH and the pH of samples measured after removal were more alkalic than those measured in vivo in the rumen (by ΔpH = 0.87 ± 0.04 and 0.26 ± 0.04). The amount of acid or base required to shift the pH of ruminal samples to 6.4 or 5.8 (base excess) differed between the 2 feeding groups. Experimental results are compared with the mathematical predictions of an open 2-buffer Henderson-Hasselbalch equilibrium model. Because pCO2 has pronounced effects on ruminal pH and can decrease rapidly in samples removed from the rumen, introduction of a generally accepted protocol for determining the acid-base status of ruminal fluid with standard levels of pCO2 and measurement of base excess in addition to pH should be considered. PMID:26519978

  13. Hydrolysis of oxaliplatin-evaluation of the acid dissociation constant for the oxalato monodentate complex.

    PubMed

    Jerremalm, Elin; Eksborg, Staffan; Ehrsson, Hans

    2003-02-01

    Alkaline hydrolysis of the platinum anticancer drug oxaliplatin gives the oxalato monodentate complex and the dihydrated oxaliplatin complex in two consecutive steps. The acid dissociation constant for the oxalato monodentate intermediate was determined by a kinetic approach. The pK(a) value was estimated as 7.23. The monodentate intermediate is assumed to rapidly react with endogenous compounds, resulting in a continuous conversion of oxaliplatin via the monodentate form. PMID:12532393

  14. Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium.

    PubMed

    Osborne, David; Lawson, Patrick; Adams, Nigel

    2014-01-21

    Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible, using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants. PMID:25669383

  15. Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium

    SciTech Connect

    Osborne, David; Lawson, Patrick; Adams, Nigel

    2014-01-21

    Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible, using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants.

  16. Dissociation constants of KSO4- from 10°-50°C

    USGS Publications Warehouse

    Truesdell, A.H.; Hostetler, P.B.

    1968-01-01

    A cell without liquid junction was used to obtain dissociation constants for the reaction: KSO4− = K+ +SO42−. At 10°, 25°, 38° and 50°C, values for Kdiss KSO4− are, respectively, 0.195, 0.142, 0.117, and 0.095. At 25°C, , and  values for the KSO4− ion are −245.96 and −274.02 kcal mole−1, and S° is +42.3 cal mole−1 deg−1.

  17. The simultaneous determination of hydrophobicity and dissociation constant by liquid chromatography-mass spectrometry.

    PubMed

    Wiczling, P; Struck-Lewicka, W; Kubik, L; Siluk, D; Markuszewski, M J; Kaliszan, R

    2014-06-01

    Convenient methods for testing drug candidates' lipophilicity and acidity are highly requested in modern pharmaceutical research and drug development strategies. Reversed-phase high-performance liquid chromatography (RP HPLC) might be particularly useful for the determination of both dissociation constant and the (pH-dependent) partition coefficient related parameters, applicable in high-throughput analysis of multi-component mixtures. The general theory of combined pH/organic modifier gradient has recently provided equations relating gradient retention time and pH of the mobile phase. The purpose of this work was to facilitate the identification of analytes in this technique by its transfer to RP HPLC coupled with time-of-flight mass spectrometry with electrospray ionization source (ESI-TOF-MS). The accuracy of the proposed methodology was assessed by analyzing a set of known drugs. The ammonium formate, ammonium acetate or ammonium bicarbonate buffers were used to control pH during chromatographic analysis. In result, the pKa and hydrophobicity parameters were determined and the accuracy of the estimated values was assessed by comparing them with literature data. The gradient RP HPLC coupled with ESI-TOF-MS methods allowed for the rapid determination of dissociation constant and hydrophobicity and was shown to be especially applicable for complex mixtures. The use of ESI-TOF-MS detection allowed to achieve the medium-throughput screening rate (100 compounds/day) and provided a simple approach to assess pharmacokinetically important physicochemical properties of drugs. PMID:24598171

  18. Dissociated nonsteroidal glucocorticoid receptor modulators; discovery of the agonist trigger in a tetrahydronaphthalene-benzoxazine series.

    PubMed

    Barker, Mike; Clackers, Margaret; Copley, Royston; Demaine, Derek A; Humphreys, Davina; Inglis, Graham G A; Johnston, Michael J; Jones, Haydn T; Haase, Michael V; House, David; Loiseau, Richard; Nisbet, Lesley; Pacquet, Francois; Skone, Philip A; Shanahan, Stephen E; Tape, Dan; Vinader, Victoria M; Washington, Melanie; Uings, Iain; Upton, Richard; McLay, Iain M; Macdonald, Simon J F

    2006-07-13

    The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described. PMID:16821781

  19. Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists.

    PubMed

    Yang, Bingwei V; Weinstein, David S; Doweyko, Lidia M; Gong, Hua; Vaccaro, Wayne; Huynh, Tram; Xiao, Hai-Yun; Doweyko, Arthur M; McKay, Lorraine; Holloway, Deborah A; Somerville, John E; Habte, Sium; Cunningham, Mark; McMahon, Michele; Townsend, Robert; Shuster, David; Dodd, John H; Nadler, Steven G; Barrish, Joel C

    2010-12-01

    A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed. PMID:21073190

  20. Measuring Kinetic Dissociation/Association Constants Between Lactococcus lactis Bacteria and Mucins Using Living Cell Probes

    PubMed Central

    Le, Doan Thanh Lam; Guérardel, Yann; Loubière, Pascal; Mercier-Bonin, Muriel; Dague, Etienne

    2011-01-01

    In this work we focused on quantifying adhesion between Lactococcus lactis, the model for lactic acid bacteria (LAB) and mucins. Interactions between two strains of L. lactis (IBB477 and MG1820 as control) and pig gastric mucin–based coating were measured and compared with the use of atomic force microscopy. Analysis of retraction force-distance curves shed light on the differential contributions of nonspecific and specific forces. An increased proportion of specific adhesive events was obtained for IBB477 (20% vs. 5% for the control). Blocking assays with free pig gastric mucin and its O-glycan moiety showed that oligosaccharides play a major (but not exclusive) role in L. lactis-mucins interactions. Specific interactions were analyzed in terms of kinetic constants. An increase in the loading rate of atomic force microscope tip led to a higher force between interacting biological entities, which was directly linked to the kinetic dissociation constant (Koff). Enhancing the contact time between the tip and the sample allowed an increase in the interaction probability, which can be related to the kinetic association constant (Kon). Variations in the loading rate and contact time enabled us to determine Kon (3.3 × 102 M−1·s−1) and Koff (0.46 s−1), and the latter was consistent with values given in the literature for sugar-protein interactions. PMID:22261074

  1. Diffusion coefficients and dissociation constants of enhanced green fluorescent protein binding to free standing membranes.

    PubMed

    Thomas, Franziska A; Visco, Ilaria; Petrášek, Zdeněk; Heinemann, Fabian; Schwille, Petra

    2015-12-01

    Recently, a new and versatile assay to determine the partitioning coefficient [Formula: see text] as a measure for the affinity of peripheral membrane proteins for lipid bilayers was presented in the research article entitled, "Introducing a fluorescence-based standard to quantify protein partitioning into membranes" [1]. Here, the well-characterized binding of hexahistidine-tag (His6) to NTA(Ni) was utilized. Complementarily, this data article reports the average diffusion coefficient [Formula: see text] of His6-tagged enhanced green fluorescent protein (eGFP-His6) and the fluorescent lipid analog ATTO-647N-DOPE in giant unilamellar vesicles (GUVs) containing different amounts of NTA(Ni) lipids. In addition, dissociation constants [Formula: see text] of the NTA(Ni)/eGFP-His6 system are reported. Further, a conversion between [Formula: see text] and [Formula: see text] is provided. PMID:26587560

  2. Determination of dissociation constants of pharmacologically active xanthones by capillary zone electrophoresis with diode array detection.

    PubMed

    Wu, Xiaomu; Gong, Suxuan; Bo, Tao; Liao, Yiping; Liu, Huwei

    2004-12-24

    In this article, the dissociation constants (pKa) of 10 pharmacologically active xanthones isolated from herbal medicine Securidaca inappendiculata were determined by capillary zone electrophoresis with diode array detection. The pKa values determined by the method based on the electrophoretic mobilities (calculated from migration times) have been proved by the method based on UV absorbance calculated from the online spectra corresponding peaks. No conspicuous difference was observed between the two methods with acceptable reproducibility. Two pKa values (pKa1 and pKa2) were found for four xanthones while generally the 10 compounds possess the pKa values ranging from 6.4 to 9.2. PMID:15641365

  3. A new sensitive method of dissociation constants determination based on the isohydric solutions principle.

    PubMed

    Michałowski, Tadeusz; Pilarski, Bogusław; Asuero, Agustin G; Dobkowska, Agnieszka

    2010-10-15

    The paper provides a new formulation and analytical proposals based on the isohydric solutions concept. It is particularly stated that a mixture formed, according to titrimetric mode, from a weak acid (HX, C(0)mol/L) and a strong acid (HB, Cmol/L) solutions, assumes constant pH, independently on the volumes of the solutions mixed, provided that the relation C(0)=C+C(2)·10(pK(1)) is valid, where pK(1)=-log K(1), K(1) the dissociation constant for HX. The generalized formulation, referred to the isohydric solutions thus obtained, was extended also to more complex acid-base systems. Particularly in the (HX, HB) system, the titration occurs at constant ionic strength (I) value, not resulting from presence of a basal electrolyte. This very advantageous conjunction of the properties provides, among others, a new, very sensitive method for verification of pK(1) value. The new method is particularly useful for weak acids HX characterized by low pK(1) values. The method was tested experimentally on four acid-base systems (HX, HB), in aqueous and mixed-solvent media and compared with the literature data. Some useful (linear and hyperbolic) correlations were stated and applied for validation of pK(1) values. Finally, some practical applications of analytical interest of the isohydricity (pH constancy) principle as one formulated in this paper were enumerated, proving the usefulness of such a property which has its remote roots in the Arrhenius concept. PMID:20875603

  4. Using Electrophoretic Mobility Shift Assays to Measure Equilibrium Dissociation Constants: GAL4-p53 Binding DNA as a Model System

    ERIC Educational Resources Information Center

    Heffler, Michael A.; Walters, Ryan D.; Kugel, Jennifer F.

    2012-01-01

    An undergraduate biochemistry laboratory experiment is described that will teach students the practical and theoretical considerations for measuring the equilibrium dissociation constant (K[subscript D]) for a protein/DNA interaction using electrophoretic mobility shift assays (EMSAs). An EMSA monitors the migration of DNA through a native gel;…

  5. Dissociation of bimolecular αIIbβ3-fibrinogen complex under a constant tensile force.

    PubMed

    Litvinov, Rustem I; Barsegov, Valeri; Schissler, Andrew J; Fisher, Andrew R; Bennett, Joel S; Weisel, John W; Shuman, Henry

    2011-01-01

    The regulated ability of integrin αIIbβ3 to bind fibrinogen plays a crucial role in platelet aggregation, adhesion, and hemostasis. Employing an optical-trap-based electronic force clamp, we studied the thermodynamics and kinetics of αIIbβ3-fibrinogen bond formation and dissociation under constant unbinding forces, mimicking the forces of physiologic blood shear on a thrombus. The distribution of bond lifetimes was bimodal, indicating that the αIIbβ3-fibrinogen complex exists in two bound states with different mechanical stability. The αIIbβ3 antagonist, abciximab, inhibited binding without affecting the unbinding kinetics, whereas Mn²(+) biased the αIIbβ3-fibrinogen complex to the strong bound state with reduced off-rate. The average bond lifetimes decreased exponentially with increasing pulling force from ∼5 pN to 50 pN, suggesting that in this force range the αIIbβ3-fibrinogen interactions are classical slip bonds. We found no evidence for catch bonds, which is consistent with the known lack of shear-enhanced platelet adhesion on fibrinogen-coated surfaces. Taken together, these data provide important quantitative and qualitative characteristics of αIIbβ3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow. PMID:21190668

  6. A rigorous multiple independent binding site model for determining cell-based equilibrium dissociation constants.

    PubMed

    Drake, Andrew W; Klakamp, Scott L

    2007-01-10

    A new 4-parameter nonlinear equation based on the standard multiple independent binding site model (MIBS) is presented for fitting cell-based ligand titration data in order to calculate the ligand/cell receptor equilibrium dissociation constant and the number of receptors/cell. The most commonly used linear (Scatchard Plot) or nonlinear 2-parameter model (a single binding site model found in commercial programs like Prism(R)) used for analysis of ligand/receptor binding data assumes only the K(D) influences the shape of the titration curve. We demonstrate using simulated data sets that, depending upon the cell surface receptor expression level, the number of cells titrated, and the magnitude of the K(D) being measured, this assumption of always being under K(D)-controlled conditions can be erroneous and can lead to unreliable estimates for the binding parameters. We also compare and contrast the fitting of simulated data sets to the commonly used cell-based binding equation versus our more rigorous 4-parameter nonlinear MIBS model. It is shown through these simulations that the new 4-parameter MIBS model, when used for cell-based titrations under optimal conditions, yields highly accurate estimates of all binding parameters and hence should be the preferred model to fit cell-based experimental nonlinear titration data. PMID:17141800

  7. Predicting both passive intestinal absorption and the dissociation constant toward albumin using the PAMPA technique.

    PubMed

    Bujard, Alban; Sol, Marine; Carrupt, Pierre-Alain; Martel, Sophie

    2014-10-15

    The parallel artificial membrane permeability assay (PAMPA) is a high-throughput screening (HTS) method that is widely used to predict in vivo passive permeability through biological barriers, such as the skin, the blood brain barrier (BBB) and the gastrointestinal tract (GIT). The PAMPA technique has also been used to predict the dissociation constant (Kd) between a compound and human serum albumin (HSA) while disregarding passive permeability. Furthermore, the assay is based on the use of two separate 5-point kinetic experiments, which increases the analysis time. In the present study, we adapted the hexadecane membrane (HDM)-PAMPA assay to both predict passive gastrointestinal absorption via the permeability coefficient logPe value and determine the Kd. Two assays were performed: one in the presence and one in the absence of HSA in the acceptor compartment. In the absence of HSA, logPe values were determined after a 4-h incubation time, as originally described, but the dimethylsulfoxide (DMSO) percentage and pH were altered to be compatible with the protein. In parallel, a second PAMPA assay was performed in the presence of HSA during a 16-h incubation period. By adding HSA, a variation in the amount of compound crossing the membrane was observed compared to the permeability measured in the absence of HSA. The concentration of compound reaching the acceptor compartment in each case was used to determine both parameters (logPe and logKd) using numerical simulations, which highlighted the originality of this method because these calculations required only two endpoint measurements instead of a complete kinetic study. It should be noted that the amount of compound that reaches the acceptor compartment in the presence of HSA is modulated by complex dissociation in the receptor compartment. Only compounds that are moderately bound to albumin (-3

  8. SARS CoV Main Proteinase: The Monomer-Dimer Equilibrium Dissociation Constant

    SciTech Connect

    Graziano,V.; McGrath, W.; Yang, L.; Mangel, W.

    2006-01-01

    The SARS coronavirus main proteinase (SARS CoV main proteinase) is required for the replication of the severe acute respiratory syndrome coronavirus (SARS CoV), the virus that causes SARS. One function of the enzyme is to process viral polyproteins. The active form of the SARS CoV main proteinase is a homodimer. In the literature, estimates of the monomer-dimer equilibrium dissociation constant, K{sub D}, have varied more than 650000-fold, from <1 nM to more than 200 {mu}M. Because of these discrepancies and because compounds that interfere with activation of the enzyme by dimerization may be potential antiviral agents, we investigated the monomer-dimer equilibrium by three different techniques: small-angle X-ray scattering, chemical cross-linking, and enzyme kinetics. Analysis of small-angle X-ray scattering data from a series of measurements at different SARS CoV main proteinase concentrations yielded K{sub D} values of 5.8 {+-} 0.8 {mu}M (obtained from the entire scattering curve), 6.5 {+-} 2.2 {mu}M (obtained from the radii of gyration), and 6.8 {+-} 1.5 {mu}M (obtained from the forward scattering). The K{sub D} from chemical cross-linking was 12.7 {+-} 1.1 {mu}M, and from enzyme kinetics, it was 5.2 {+-} 0.4 {mu}M. While each of these three techniques can present different, potential limitations, they all yielded similar K{sub D} values.

  9. Potentiometric determination of the dissociation constants of an asymmetric sorbent containing l-proline, and the stability constants of its Cu(II) complexes.

    PubMed

    Zolotarev, Y A; Kurganov, A A; Davankov, V A

    1978-09-01

    The dissociation constants of the carboxyl groups (pK(a1) = 2.2, n = 1.8) and amino groups (pK(a2) = 9.5, n(2) = 1.6) of a sorbent prepared by reacting l-proline with a cross-linked chloromethylated styrene polymer have been determined by potentiometric titration. The potentiometrically measured stability constants of the Cu(II) complexes of the resin (logbeta(1) = 6.9 and log beta(2) = 12.4) were found to be close to the values for the Cu(II) complexes of N-benzyl-l-proline. For complexed resins of alpha-amino-acid type the pH-values of decomplexation do not appear to be directly correlated with the stability constants. PMID:18962307

  10. Determination of the dissociation constants of the cephalosporins cefepime and cefpirome using UV spectrometry and pH potentiometry.

    PubMed

    Evagelou, Vassilis; Tsantili-Kakoulidou, Anna; Koupparis, Michael

    2003-04-10

    UV spectrometry and pH potentiometry were used for the determination and direct characterization of the dissociation constants of cefepime (Cef) and cefpirome. The absorbance/pH profiles at two analytical wavelengths and different conditions were assessed and found to conform to those of diprotic acids. The titration curves indicated a triprotic acid profile with two overlapping dissociation constants. The comparison of the results of both techniques permitted the direct attribution of the three dissociation constants to the carboxylic group at position 4 of the Delta-3 cephem nucleus, the aminothiazole group and the amide group at position 7 of the Delta-3 cephem nucleus. Stability studies of Cef in alkaline solutions were also performed in order to evaluate the accuracy of the measurements carried out for the determination of the third pK(a) value. The experimental pK(a) values were compared to the corresponding predicted values derived by PALLAS/PKALC and Advanced Chemical Development (ACD) software packages. PMID:12667928

  11. Predicting the probability of successful efficacy of a dissociated agonist of the glucocorticoid receptor from dose-response analysis.

    PubMed

    Conrado, Daniela J; Krishnaswami, Sriram; Shoji, Satoshi; Kolluri, Sheela; Hey-Hadavi, Judith; McCabe, Dorothy; Rojo, Ricardo; Tammara, Brinda K

    2016-06-01

    PF-04171327 is a dissociated agonist of the glucocorticoid receptor (DAGR) being developed to retain anti-inflammatory efficacy while reducing unwanted effects. Our aim was to conduct a longitudinal dose-response analysis to identify the DAGR doses with efficacy similar to or greater than prednisone 10 mg once daily (QD). The data included were from a Phase 2, randomized, double-blind, parallel-group study in 323 subjects with active rheumatoid arthritis on a background of methotrexate. Subjects received DAGR 1, 5, 10 or 15 mg, prednisone 5 or 10 mg, or placebo QD for 8 weeks. The Disease Activity Score 28-4 calculated using C-Reactive Protein (DAS28-4 CRP) was the efficacy endpoint utilized in this dose-response model. For DAGR, the maximum effect (Emax) on DAS28-4 CRP was estimated to be -1.2 points (95 % CI -1.7, -0.84), and the evaluated dose range provided 31-87 % of the Emax; for prednisone 5 and 10 mg, the estimated effects were -0.27 (95 % CI -0.55, 0.006) and -0.94 point (95 % CI -1.3, -0.59), respectively. Stochastic simulations indicated that the DAGR 1, 5, 10 and 15 mg have probabilities of 0.9, 29, 54 and 62 %, respectively, to achieve efficacy greater than prednisone 10 mg at week 8. DAGR 9 mg estimated probability was 50 % suggesting that DAGR ≥9 mg QD has an effect on DAS28-4 CRP comparable to or greater than prednisone 10 mg QD. This work informs dose selection for late-stage confirmatory trials. PMID:27178257

  12. Determination of Acid Dissociation Constants (pKa) of Bicyclic Thiohydantoin-Pyrrolidine Compounds in 20% Ethanol-Water Hydroorganic Solvent

    PubMed Central

    Nural, Yahya; Döndaş, H. Ali; Sarı, Hayati; Atabey, Hasan; Belveren, Samet; Gemili, Müge

    2014-01-01

    The acid dissociation constants of potential bioactive fused ring thiohydantoin-pyrrolidine compounds were determined by potentiometric titration in 20% (v/v) ethanol-water mixed at 25 ± 0.1°C, at an ionic background of 0.1 mol/L of NaCl using the HYPERQUAD computer program. Proton affinities of potential donor atoms of the ligands were calculated by AM1 and PM3 semiempiric methods. We found, potentiometrically, three different acid dissociation constants for 1a–f. We suggest that these acid dissociation constants are related to the carboxyl, enol, and amino groups. PMID:24799905

  13. Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation

    PubMed Central

    McNeil, Lisa K.; Evavold, Brian D.

    2002-01-01

    We have focused on stability of the peptide-MHC complex as a determining factor of ligand potency for thymocytes and peripheral CD4+ T cell responses. MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists) but do not induce thymocyte negative selection. The MHC variant weak agonists require significant receptor reserve, because decreasing the level of T cell receptor on mature T cells blocks the proliferative response. These results demonstrate that peripheral T cells are more sensitive to MHC variant ligands by virtue of increased T cell receptor expression; in addition, the data support a T cell model of the spare receptor theory. PMID:11904393

  14. Dynamic titration: determination of dissociation constants for noncovalent complexes in multiplexed format using HPLC-ESI-MS.

    PubMed

    Frycák, Petr; Schug, Kevin A

    2008-03-01

    With recent growth in fields such as life sciences and supramolecular chemistry, there has been an ever increasing need for high-throughput methods that would permit determination of binding affinities for noncovalent complexes of various host-guest systems. These are traditionally measured by titration experiments where concentration-dependent signals of species participating in solution-based binding equilibria are monitored by methods such as UV-vis spectrophotometry, calorimetry, or nuclear magnetic resonance spectrometry. Here we present a new titration technique that unifies and allows chromatographic separation of guests with determination of dissociation constants by electrospray mass spectrometry in a multiplexed format. A theoretical model has been derived that describes the complex formation for the guests eluted from a chromatographic column when hosts are admixed postcolumn. The model takes possible competition equilibria into account; i.e., it can deal with unresolved peaks of guests with the possible addition of multiple hosts in one experiment. This on-line workflow makes determination of binding affinities for large libraries of compounds possible. The potential of the method is demonstrated on the determination of dissociation constants for complexes of beta- and gamma-cyclodextrins with nonsteroidal antiinflammatory drugs ibuprofen, naproxen, and flurbiprofen. PMID:18237190

  15. Studies on the collision-induced dissociation of adipoR agonists after electrospray ionization and their implementation in sports drug testing.

    PubMed

    Dib, Josef; Schlörer, Nils; Schänzer, Wilhelm; Thevis, Mario

    2015-02-01

    AdipoR agonists are small, orally active molecules capable of mimicking the protein adiponectin, which represents an adipokine with antidiabetic and antiatherogenic effects. Two adiponectin receptors were reported in the literature referred to as adipoR1 and adipoR2. Activation of these receptors stimulates mitochondrial biogenesis and results in an improved oxidative metabolism (via adipoR1) and increased insulin sensitivity (via adipoR2). Hence, adipoR agonists are potentially performance enhancing substances and targets of proactive and preventive anti-doping measures. In this study, two adipoR agonists termed AdipoRon and 112254 as well as two isotopically labeled internal standards (ISTDs) were synthesized in three-step reactions. The products were fully characterized by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) computation. Collision-induced dissociation pathways following electrospray ionization were suggested based on the determined elemental compositions of product ions, comparison to product ions derived from labeled analogs (ISTDs), H/D-exchange experiments and the results of DFT calculations. The most abundant product ions were found at m/z 174, tentatively assigned to protonated 1-benzyl-1,2,3,4-tetrahydropyridine for AdipoRon, and m/z 207, suggested as protonated 1-(4-methoxybenzyl)piperazine, for 112254. Notably, the loss of the heterocyclic ring (i.e. piperazine and piperidine, respectively) in a supposedly intramolecular elimination reaction was observed in both cases. A qualitative determination of both AdipoR agonists in human plasma was established and fully validated for doping control purposes. Validation items such as recovery (86-89%), specificity, linearity, lower limit of detection (1 ng/ml), intraday (3-18%) and interday (5-16%) precision as well as ion suppression or enhancement were determined. Based on these findings adipoR agonists can be implemented in sports drug

  16. Effect of pressure on the dissociation constant of boric acid in water and seawater

    NASA Astrophysics Data System (ADS)

    Millero, Frank J.; Ward, Gary K.; Surdo, Antonio Lo; Huang, Fen

    2012-01-01

    The sound speeds of boric acid and sodium borate in water and 0.725 m NaCl have been measured from 0 to 50 °C and to near 1 molal. These results have been used to determine the partial molal adiabatic compressibilities of B(OH) 3 and NaB(OH) 4. The partial molal volumes, v¯(i), and compressibilities, κ¯(i), have been used to estimate the changes in the volume (Δ V) and compressibility (Δ κ) for the dissociation of boric acid in water and average seawater (0.725 m NaCl, SA ˜ 35 g/kg) B(OH)3+H2O=H++B(OH)4- where

  17. Distribution of proton dissociation constants for model humic and fulvic acid molecules.

    PubMed

    Atalay, Yasemin B; Carbonaro, Richard F; Di Toro, Dominic M

    2009-05-15

    The intrinsic proton binding constants of 10 model humic acid and six model fulvic acid molecules are calculated using SPARC Performs Automated Reasoning in Chemistry (SPARC). The accuracy of the SPARC calculations is examined using estimated microscopic binding constants of various small organic acids. An equimolar mixture of the appropriate hypothetical molecules is used as a representation of soil and aqueous humic acid and fulvic acid. The probability distributions of the mixture microscopic proton binding constants and the intrinsic proton binding constants in the metal speciation models WHAM V and WHAM VI (Windermere humic aqueous models) are compared. The idea is to assess the predictive value of the molecular mixture models as representations of heterogeneous natural organic matter. For aqueous humic and fulvic acids, the results are comparable to the WHAM distribution. For soil humic acid, the WHAM probability distribution is less acidic for the carboxylic sites but similar to that of the phenolic sites. Computations made using the WHAM molecular distributions and WHAM VI are comparable to titration data for Suwannee River fulvic acid. These results suggest that mixture molecular models can be used to investigate and predict the binding of metal cations to humic and fulvic acids. PMID:19544864

  18. Dissociation and rate constants of some human liver alcohol dehydrogenase isoenzymes.

    PubMed

    Pietruszko, R; de Zalenski, C; Theorell, H

    1976-01-01

    ADH from human liver forms binary complexes with NADH, associated with a blue shift of the peak of the fluorescence emission of NADH. The wavelength shift is the same for all isoenzymes but the accompanying intensification of the fluorescence is different. The fluorescence is further increased by the formation of the very tight ternary enzyme-NADH-isobutyramide complexes. These properties are similar to those for the horse liver ADH, as well as the molecular weight of E=40 000 per active site of the dimer molecule (EE). "Stopped-flow" determined velocity constants (ER in equilibrium E+R) were found to be in good agreement with ethanol activity constants previously determined by activity measurement, confirming the validity of the ordered ternary complex mechanism also for the human ADH. No single isoenzyme activity as high as that reported by Mourad and Woronick or Drum has been found. PMID:184631

  19. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations

    NASA Astrophysics Data System (ADS)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.

    2016-09-01

    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase ( PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  20. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations.

    PubMed

    Pedro, Liliana; Van Voorhis, Wesley C; Quinn, Ronald J

    2016-09-01

    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each. Graphical Abstract ᅟ. PMID:27225419

  1. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations

    NASA Astrophysics Data System (ADS)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.

    2016-05-01

    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  2. Direct measurement via phage titre of the dissociation constants in solution of fusion phage-substrate complexes.

    PubMed Central

    Dyson, M R; Germaschewski, V; Murray, K

    1995-01-01

    Studies of interactions between filamentous fusion phage particles and protein or nucleic acid molecules have gained increasing importance with recent successes of screening techniques based upon random phage display libraries (biopanning). Since a number of different phage are usually obtained by biopanning, it is useful to compare quantitatively the binding affinities of individual phage for the substrate used for selection. A procedure is described for determination of relative dissociation constants (KdRel) between filamentous phage carrying peptide fusions to the coat protein gpIII and substrates in solution. This novel method is based on the measurement of phage titres. Phage selected from a random fusion phage library for binding to a monoclonal antibody or a viral structural protein exhibited KdRel values in the nanomolar and micromolar ranges for their respective substrates, thus validating the method over a wide range of binding affinities. PMID:7784206

  3. The autoxidation and proton dissociation constants of tertiary diphosphines: relevance to biological activity.

    PubMed

    Berners-Price, S J; Norman, R E; Sadler, P J

    1987-11-01

    The pKas and autoxidation properties of a number of diphosphines which exhibit varying degrees of antitumor and cytotoxic activity were investigated. Titration by HClO4 in CH3NO2 was used to determine pKas of the following diphosphines: R2P(CH2)nPR'2, where for R = R' = Ph, n = 1, 2, and 3 (dppm, dppe, and dppp respectively); for R = R' = Et, n = 2 (depe); for R = Ph, R' = Et, n = 2 (eppe); and for cis and trans Ph2PCH = CHPPh2 (dppey). The difference between the first and second protonation constants decreases as the length of the carbon chain between the two phosphorus centers increases. Unsaturation in the carbon chain lowers pKas. -PEt2 centers are apparently more basic than -PPh2 centers. Apart from electrostatic effects, the protonation of a given phosphine center appears to be independent of the substituents at the second phosphine center. The autoxidation reactions of dppm, dppe, dppp, depe, and cis-dppey were studied in a variety of solvents by 31P NMR spectroscopy. The ethyl-substituted diphosphines were much more rapidly oxidized than the phenyl-substituted, and the pathways of autoxidation differed. Generally, the phenyl-substituted diphosphines gave only mono- and dioxides, while the ethyl-substituted diphosphines additionally gave phosphinites and other oxidation products. The relevance of the autoxidation reactivity and the pKas to the contrasting antitumor activity of these diphosphines is discussed. PMID:2828542

  4. Calculation of rate constants for dissociative attachment of low-energy electrons to hydrogen halides HCl, HBr, and HI and their deuterated analogs

    SciTech Connect

    Houfek, Karel; Cizek, Martin; Horacek, Jiri

    2002-12-01

    Calculations of rate constants for the process of dissociative attachment of low-energy electrons to hydrogen halides HCl, HBr, and HI and for the reverse process of associative detachment based on the nonlocal resonance model are reported. The calculated data are of importance for the modeling of plasma processes, environmental chemistry, etc. The calculated dissociative attachment rate constants are found to be in good agreement with existing experimental data. It is shown that at low temperatures the rate constants are very sensitive to small changes of the parameters of the nonlocal resonance model used for the calculation of the rate constants and represent a severe test of the theory. The isotopic effect and its dependence on the temperature is also discussed. The calculations of rate constants for the reverse process of associative detachment are also reported and discussed.

  5. Detection analysis of surface hydroxyl active sites and simulation calculation of the surface dissociation constants of aqueous diatomite suspensions

    NASA Astrophysics Data System (ADS)

    Ma, Shu-Cui; Wang, Zhi-Gang; Zhang, Ji-Lin; Sun, De-Hui; Liu, Gui-Xia

    2015-02-01

    The surface properties of the diatomite were investigated using nitrogen adsorption/deadsorption isotherms, TG-DSC, FTIR, and XPS, and surface protonation-deprotonation behavior was determined by continuous acid-base potentiometric titration technique. The diatomite sample with porous honeycomb structure has a BET specific surface area of 10.21 m2/g and large numbers of surface hydroxyl functional groups (i.e. tbnd Si-OH, tbnd Fe-OH, and tbnd Al-OH). These surface hydroxyls can be protonated or deprotonated depending on the pH of the suspension. The experimental potentiometric data in two different ionic strength solutions (0.1 and 0.05 mol/L NaCl) were fitted using ProtoFit GUI V2.1 program by applying diffuse double layer model (DLM) with three amphoteric sites and minimizing the sum of squares between a dataset derivative function and a model derivative function. The optimized surface parameters (i.e. surface dissociation constants (log K1, log K2) and surface site concentrations (log C)) of the sample were obtained. Based on the optimized surface parameters, the surface species distribution was calculated using Program-free PHREEQC 3.1.2. Thus, this work reveals considerable new information about surface protonation-deprotonation processes and surface adsorptive behaviors of the diatomite, which helps us to effectively use the cheap and cheerful diatomite clay adsorbent.

  6. Determination of acid dissociation constant of 20 coumarin derivatives by capillary electrophoresis using the amine capillary and two different methodologies.

    PubMed

    Nowak, Paweł Mateusz; Woźniakiewicz, Michał; Piwowarska, Monika; Kościelniak, Paweł

    2016-05-13

    In this work capillary electrophoresis has been used to determine acid dissociation constant of 20 structurally diverse coumarin derivatives. For a majority of compounds pKa value has been determined for the first time. The obtained values vary between 4.16-9.10pH unit, pointing to the interesting structure-acidity relationships. The amine permanently coated capillary has been applied for that purpose, because it has turned out to be more effective in pKa determination than the bare silica and other coated capillaries, ensuring good precision and shorter migration times. A traditional methodology relying on measurements in a broad pH range and fitting of a sigmoidal function has been compared to an alternative simplified approach, reported for the first time, where only two electrophoretic mobility values suffice for pKa estimation. The first value corresponds to the partially ionized form and it is measured experimentally, while the second one to the totally ionized form - it is measured experimentally (two-values method) or estimated directly from molecular mass (one-value method). We show that despite a limited measurements number, the alternative approach may be consistent with the traditional methodology, yielding the relatively low pKa deviation. Its reliability has also been confirmed by the analytical predictions, comprising resolution, migration order, migration times and peaks overlapping. Therefore, combination of the amine capillary with the simplified calculation method is an attractive tool for fast and reliable pKa estimation. PMID:27083264

  7. Apparent Ca2+ dissociation constant of Ca2+ chelators incorporated non-disruptively into intact human red cells.

    PubMed Central

    Tiffert, T; Lew, V L

    1997-01-01

    1. A recently developed method of measuring cytoplasmic Ca2+ buffering in intact red cells was applied to re-evaluate the intracellular Ca2+ binding properties of the Ca2+ chelators benz2 and BAPTA. Incorporation of the free chelators was accomplished by incubating the cells with the acetoxymethyl ester forms (benz2 AM or BAPTA AM). The divalent cation ionophore A23187 was used to induce equilibrium distribution of Ca2+ between cells and medium. 45Ca2+ was added stepwise to cell suspensions in the presence and absence of external BAPTA. To induce full Ca2+ equilibration, the plasma membrane Ca2+ pump was inhibited either by depleting the cells of ATP or by adding vanadate to the cell suspension. 2. The properties of the incorporated chelators were assessed from the difference in cytoplasmic Ca2+ buffering between chelator-free and chelator-loaded cells, over a wide range of intracellular ionized calcium concentrations ([Ca2+]i), from nanomolar to millimolar. 3. Under the experimental conditions applied, incorporation of benz2 and BAPTA into the red cells increased their Ca2+ buffering capacity by 300-600 mumol (340 g Hb)-1. The intracellular apparent Ca2+ dissociation constants (KDi) were about 500 nM for benz2 and 800 nM for BAPTA, values much higher than those reported for standard salt solutions (KD) of about 40 and 130 nM, respectively. These results suggest that, contrary to earlier observations, the intracellular red cell environment may cause large shifts in the apparent Ca2+ binding behaviour of incorporated chelators. 4. The possibility that the observed KD shifts are due to reversible binding of the chelators to haemoglobin is considered, and the implications of the present results for early estimates of physiological [Ca2+]i levels is discussed. PMID:9423182

  8. The proton dissociation constant of additive effect on self-assembly of poly(3-hexyl-thiophene) for organic solar cells

    NASA Astrophysics Data System (ADS)

    Wang, Po-Hsun; Lee, Hsu-Feng; Huang, Yi-Chiang; Jung, Yi-Jiun; Gong, Fang-Lin; Huang, Wen-Yao

    2014-07-01

    In the decision on the pros and cons of the optical and electrical properties of organic solar cells, the morphology has proven to be very important. Easy to change the morphology via adding a small amount of additive, because proton dissociation constant is the main reason for their application. In this study, the use of poly(3-hexylthiophene) and [6,6]-phenyl C 61-butyric acid methyl ester as the donor and acceptor materials, and were subsequently doped with different quantity of 4,4'-sulfonyldiphenol, 4,4'-dihydroxybiphenyl, biphenyl-4,4'-dithiol. When the proton dissociation constant is higher and lower respectively, the morphology reveals earthworms-like and fiber-like. For the reason that when the additive is biphenyl-4,4'-dithiol, it can improve the power conversion efficiency of about 27% and the incident photon-to-current conversion efficiency of about 12%.

  9. The dissociation constants of the cytostatic bosutinib by nonlinear least-squares regression of multiwavelength spectrophotometric and potentiometric pH-titration data.

    PubMed

    Meloun, Milan; Nečasová, Veronika; Javůrek, Milan; Pekárek, Tomáš

    2016-02-20

    Potentiometric and spectrophotometric pH-titration of the multiprotic cytostatics bosutinib for dissociation constants determination were compared. Bosutinib treats patients with positive chronic myeloid leukemia. Bosutinib exhibits four protonatable sites in a pH range from 2 to 11, where two pK are well separated (ΔpK>3), while the other two are near dissociation constants. In the neutral medium, bosutinib occurs in the slightly water soluble form LH that can be protonated to the soluble cation LH4(3+). The molecule LH can be dissociated to still difficultly soluble anion L(-). The set of spectra upon pH from 2 to 11 in the 239.3-375.0nm was divided into two absorption bands: the first one from 239.3 to 290.5nm and the second from 312.3 to 375.0nm, which differ in sensitivity of chromophores to a pH change. Estimates of pK of the entire set of spectra were compared with those of both absorption bands. Due to limited solubility of bosutinib the protonation in a mixed aqueous-methanolic medium was studied. In low methanol content of 3-6% three dissociation constants can be reliably determined with SPECFIT/32 and SQUAD(84) and after extrapolation to zero content of methanol they lead to pKc1=3.43(12), pKc2=4.54(10), pKc3=7.56(07) and pKc4=11.04(05) at 25°C and pKc1=3.44(06), pKc2=5.03(08) pKc3=7.33(05) and pKc4=10.92(06) at 37°C. With an increasing content of methanol in solvent the dissociation of bosutinib is suppressed and the percentage of LH3(2+) decreases and LH prevails. From the potentiometric pH-titration at 25°C the concentration dissociation constants were estimated with ESAB pKc1=3.51(02), pKc2=4.37(02), pKc3=7.97(02) and pKc4=11.05(03) and with HYPERQUAD: pKc1=3.29(12), pKc2=4.24(10), pKc3=7.95(07) and pKc4=11.29(05). PMID:26730513

  10. (/sup 3/H)dihydroergotamine as a high-affinity, slowly dissociating radioligand for 5-HT1B binding sites in rat brain membranes: evidence for guanine nucleotide regulation of agonist affinity states

    SciTech Connect

    Hamblin, M.W.; Ariani, K.; Adriaenssens, P.I.; Ciaranello, R.D.

    1987-12-01

    (/sup 3/H)Dihydroergotamine (DE) labels a population of binding sites in rat brain membranes with an affinity of approximately 70 pM in both hippocampus (maximal binding at saturation (Bmax) = 340 fmol/mg of protein) and cerebral cortex (Bmax = 250 fmol/mg of protein). Specific binding typically comprises about 97% of total binding at the Kd of the radioligand when nonspecific binding is determined in the presence of 100 nM unlabeled DE. Association kinetics at 37 degrees C are consistent with a uniform association rate constant for all sites labeled. Specific binding is completely reversible with addition of excess unlabeled DE, but dissociation does not proceed with simple first-order kinetics, suggesting the presence of more than one discrete binding site. Competition studies with selective drugs reveal alpha adrenergic, 5-HT1A and 5-HT1B components of (/sup 3/H)DE specific binding. When phentolamine (500 nM) is included to block alpha receptors and DPAT (100 nM) or spiroxatrine (500 nM) is included to block 5-HT1A receptors, specific binding is exclusively to sites with drug affinities characteristic of 5-HT1B receptors. Under these 5-HT1B-selective conditions, (/sup 3/H)DE binding is about 90% specific, with a Kd of about 50 to 60 pM and a Bmax of 96 fmol/mg of protein in hippocampus and 77 fmol/mg of protein in cortex. (/sup 3/H)DE binding to 5-HT1B sites is very slowly dissociable, with a T1/2 of greater than 2 h at 37 degrees C. 5-HT1B antagonists and DE itself yield competition curves at (/sup 3/H)DE-labeled 5-HT1B sites that are adequately fit assuming a single site in nonlinear regression analysis. Addition of 100 microM guanylyl 5'-imidodiphosphate appears to convert nearly all 5-HT1B sites to those having low affinity for agonists while having a much smaller effect on the binding of (/sup 3/H)DE.

  11. The thermodynamic dissociation constants of four non-steroidal anti-inflammatory drugs by the least-squares nonlinear regression of multiwavelength spectrophotometric pH-titration data.

    PubMed

    Meloun, Milan; Bordovská, Sylva; Galla, Lubomír

    2007-11-30

    The mixed dissociation constants of four non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac sodium, flurbiprofen and ketoprofen at various ionic strengths I of range 0.003-0.155, and at temperatures of 25 degrees C and 37 degrees C, were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT/32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis. The factor analysis in the INDICES program predicts the correct number of components, and even the presence of minor ones, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant pK(a)(T) was estimated by nonlinear regression of (pK(a), I) data at 25 degrees C and 37 degrees C. Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. PALLAS, MARVIN, SPARC, ACD/pK(a) and Pharma Algorithms predict pK(a) being based on the structural formulae of drug compounds in agreement with the experimental value. The best agreement seems to be between the ACD/pK(a) program and experimentally found values and with SPARC. PALLAS and MARVIN predicted pK(a,pred) values with larger bias errors in comparison with the experimental value for all four drugs. PMID:17825517

  12. Simultaneous determination of hydrophobicity and dissociation constant for a large set of compounds by gradient reverse phase high performance liquid chromatography-mass spectrometry technique.

    PubMed

    Kubik, Łukasz; Struck-Lewicka, Wiktoria; Kaliszan, Roman; Wiczling, Paweł

    2015-10-16

    Fast and reliable methods for the determination of hydrophobicity and acidity are desired in pre-clinical drug development phases to eliminate compounds with poor pharmacokinetic properties. Reversed-phase high-performance liquid chromatography (RP HPLC) coupled with time-of-flight mass spectrometry (RP HPLC-ESI-TOF-MS) is a convenient technique for that purpose. In this work we determined the chromatographic measure of hydrophobicity (logkw) and dissociation constant (pKa) simultaneously for a large and diverse group of 161 drugs. Retention times were determined by means of RP HPLC-ESI-TOF-MS for a series of pH and organic modifier gradients. We were able to measure retention times for 140 out of 161 (87%) compounds. For those analytes logkw and pKa parameters were calculated and compared with literature and ACD Labs-calculated data. The determined chromatographic measure of hydrophobicity and dissociation constant was closely related to literature and theoretically calculated values. Applied methodology achieved the medium-throughput screening rate of 100 compounds per day and proved to be a simple, fast and reliable approach of assessing important physicochemical properties of drugs. This technique has certain limitations as it is not applicable for very hydrophilic analytes (logP<0.5) and compounds with identical molar masses. PMID:26365909

  13. Strong ion difference excess and corrected strong ion difference model incorporating the variations in apparent dissociation constant for human blood plasma electro-neutrality equilibria.

    PubMed

    Rana, Amar P S; Rana, Sam Pal; Rana, Jay Pal; Singh, Sumarjeet

    2006-01-01

    We introduce computed value of the corrected Strong Ion Difference (SID) by including the large variability of the apparent dissociation constant pK' in non-logarithmic form on SID in Henderson-Hasselbach bicarbonate ion aqueous equilibria thereby resulting in a significant correction of up to 27% in SID. We further introduce a new concept of Strong Ion Difference Excess (SIDE) as the change in SID from the reference value at pH = 7.4, pCO2 = 5.33 Kpa (or 40 torr). The SIDE is a particularly useful quick measure when one can rule out the effects of hemoglobin, weak proteins and unidentified components for human blood plasma. PMID:17051730

  14. Potential misevaluation of the ground-state dissociation constant from fluorimetric titrations: application to the ion indicators SBFI, PBFI, and fura-2.

    PubMed

    Kowalczyk, A; Boens, N; Meuwis, K; Ameloot, M

    1997-02-01

    A test based on time-resolved fluorescence experiments is proposed to assess the interference of an excited-state reaction with the fluorimetric determination of the ground-state dissociation constant Kd of ion [symbol: see text] fluorescent indicator complexes. If an inflection point occurs in the plot of the fluorescence signal vs -log [ion] in the concentration range of the ion where both decay times are invariant, this inflection point can be associated with the correct Kd. In contrast, the inflection point(s) in the concentration range where the decay times vary cannot be attributed to Kd. The test is applied to the fluorescent ion indicators SBFI (for Na+), PBFI (for K+), and Fura-2 (for Ca2+). In all three cases the decay times are invariant in the physiological concentration ranges of the respective ions, indicating that the fluorimetrically determined Kd values are actually the true Kd values. PMID:9025965

  15. Fractionation of oil sands-process affected water using pH-dependent extractions: a study of dissociation constants for naphthenic acids species.

    PubMed

    Huang, Rongfu; Sun, Nian; Chelme-Ayala, Pamela; McPhedran, Kerry N; Changalov, Mohamed; Gamal El-Din, Mohamed

    2015-05-01

    The fractionation of oil sands process-affected water (OSPW) via pH-dependent extractions was performed to quantitatively investigate naphthenic acids (NAs, CnH2n+ZO2) and oxidized NAs (Ox-NAs) species (CnH2n+ZO3 and CnH2n+ZO4) using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS). A mathematical model was also developed to estimate the dissociation constant pKa for NAs species, considering the liquid-liquid extraction process and the aqueous layer acid-base equilibrium. This model provides estimated dissociation constants for compounds in water samples based on fractionation extraction and relative quantification. Overall, the sum of O2-, O3-, and O4-NAs species accounted for 33.6% of total extracted organic matter. Accumulative extracted masses at different pHs revealed that every oxygen atom added to NAs increases the pKa (i.e., O2-NAs

  16. Quantification of chemical states, dissociation constants and contents of oxygen-containing groups on the surface of biochars produced at different temperatures.

    PubMed

    Chen, Zaiming; Xiao, Xin; Chen, Baoliang; Zhu, Lizhong

    2015-01-01

    Surface functional groups such as carboxyl play a vital role in the environmental applications of biochar as a soil amendment. However, the quantification of oxygen-containing groups on a biochar surface still lacks systematical investigation. In this paper, we report an integrated method combining chemical and spectroscopic techniques that were established to quantitatively identify the chemical states, dissociation constants (pK(a)), and contents of oxygen-containing groups on dairy manure-derived biochars prepared at 100-700 °C. Unexpectedly, the dissociation pH of carboxyl groups on the biochar surface covered a wide range of pH values (pH 2-11), due to the varied structural microenvironments and chemical states. For low temperature biochars (≤ 350 °C), carboxyl existed not only as hydrogen-bonded carboxyl and unbonded carboxyl groups but also formed esters at the surface of biochars. The esters consumed OH(-) via saponification in the alkaline pH region and enhanced the dissolution of organic matter from biochars. For high temperature biochars (≥ 500 °C), esters came from carboxyl were almost eliminated via carbonization (ester pyrolysis), while lactones were developed. The surface density of carboxyl groups on biochars decreased sharply with the increase of the biochar-producing temperature, but the total contents of the surface carboxyls for different biochars were comparable (with a difference <3-fold) as a result of the expanded surface area at high pyrolytic temperatures. Understanding the wide pKa ranges and the abundant contents of carboxyl groups on biochars is a prerequisite to recognition of the multifunctional applications and biogeochemical cycling of biochars. PMID:25453912

  17. Determination of dissociation constant of the NFκB p50/p65 heterodimer using fluorescence cross-correlation spectroscopy in the living cell

    SciTech Connect

    Tiwari, Manisha; Mikuni, Shintaro; Muto, Hideki; Kinjo, Masataka

    2013-07-05

    Highlights: •We used two-laser-beam FCCS to determine the dissociation constant (K{sub d}) of IPT domain of p50/p65 heterodimer in living cell. •Interaction of p50 and p65 was analyzed in the cytoplasm and nucleus of single living cell. •Binding affinity of p50/p65 heterodimer is higher in cytoplasm than that of nucleus. -- Abstract: Two-laser-beam fluorescence cross-correlation spectroscopy (FCCS) is promising technique that provides quantitative information about the interactions of biomolecules. The p50/p65 heterodimer is the most abundant and well understood of the NFκB dimers in most cells. However, the quantitative value of affinity, namely the K{sub d}, for the heterodimer in living cells is not known yet. To quantify the heterodimerization of the IPT domain of p50/p65 in the living cell, we used two-laser-beam FCCS. The K{sub d} values of mCherry{sub 2}- and EGFP-fused p50 and p65 were determined to be 0.46 μM in the cytoplasm and 1.06 μM in the nucleus of the living cell. These results suggest the different binding affinities of the p50/p65 heterodimer in the cytoplasm and nucleus of the living cell and different complex formation in each region.

  18. Preferential solvation of perfluorooctanoic acid (PFOA) by methanol in methanol-water mixtures: A potential overestimation of the dissociation constant of PFOA using a Yasuda-Shedlovsky plot

    NASA Astrophysics Data System (ADS)

    Kutsuna, Shuzo; Hori, Hisao; Sonoda, Takaaki; Iwakami, Toru; Wakisaka, Akihiro

    2012-03-01

    Solvation of perfluorooctanoic acid (PFOA) in methanol-water mixed solvents was investigated by means of the mass spectrometric analyses of clusters in the solutions. The observed clusters were composed of PFOA, methanol, and water molecules. The molecular composition of the clusters showed that PFOA was preferentially solvated by methanol in the methanol-water mixed solvents, and that the ratio of methanol molecules in the PFOA solvation sphere was beyond 0.6 at the bulk methanol mole fraction (xMeOH) = 0.045. The microscopic environment of PFOA was almost occupied by the methanol from such lower xMeOH (xMeOH ≥ 0.045), and hence the ratio of methanol in the PFOA solvation sphere did not change at xMeOH ≥ 0.045 as much as the bulk xMeOH. This preferential solvation of PFOA by methanol suggested a potential overestimation on the dissociation constant (pKa) of PFOA extrapolated from a Yasuda-Shedlovsky plot.

  19. Application of chemometrics in determination of the acid dissociation constants (pKa) of several benzodiazepine derivatives as poorly soluble drugs in the presence of ionic surfactants.

    PubMed

    Shayesteh, Tavakol Heidary; Radmehr, Moojan; Khajavi, Farzad; Mahjub, Reza

    2015-03-10

    In this study, the acid dissociation constants (pKa) of some benzodiazepine derivatives including chlordiazepoxide, clonazepam, lorazepam, and oxazepam in aqueous micellar solution were determined spectrophotometrically at an ionic strength of 0.1M at 25°C. The effect of cetyl trimethylammonium bromide (CTAB) as a cationic and sodium n-dodecyl sulfate(SDS) as an anionic surfactant on the absorption spectra of benzodiazepine drugs at different pH values were studied. The acidity constants of all related species are estimated by considering the surfactant concept and the application of chemometric methods using the whole spectral fitting of the collected data to an established factor analysis model. DATAN® software (Ver. 5.0, Multid Analyses AB, and Goteborg, Sweden) was applied to determine the acidity constants. In this study, a simple and fast method to determine the ionization constant (pKa) of poorly soluble drugs was developed using surfactants. The acidity constant (i.e. pKa) for chlordiazepoxide, clonazepam, lorazepam, and oxazepam were reported as 4.62, pKa1 value of 1.52 and pKa2 value of 10.51, pKa1 value of 1.53 and pKa2 value of 10.92 and pKa1 value 1.63 and pKa2 value of 11.21 respectively. The results showed that the peak values in the spectrophotometric absorption spectra of drugs are influenced by the presence of anionic and cationic surfactants. According to the results, by changing the SDS concentration from 0 to 0.05M, the pKa of chlordiazepoxide was increased to 5.9, the pKa1 of lorazepam was decreased to 0.1 while the pKa2 was increased to 11.5. Increase in SDS concentration has not shown significant alteration in pKa of clonazepam and oxazepam. Results indicate that by Changing the CTAB concentration from 0 to 0.05M, the pKa of chlordiazepoxide was reduced to 4.4, the pKa1 of clonazepam was decreased to 0.1 and the pKa2 was decreased to 9.1, the pKa1 of lorazepam was decreased to 0.4 and the pKa2 was decreased to 9.4, the pKa1 of oxazepam was

  20. Dissociations in the Effects of β2-Adrenergic Receptor Agonists on cAMP Formation and Superoxide Production in Human Neutrophils: Support for the Concept of Functional Selectivity

    PubMed Central

    Brunskole Hummel, Irena; Reinartz, Michael T.; Kälble, Solveig; Burhenne, Heike; Schwede, Frank; Buschauer, Armin; Seifert, Roland

    2013-01-01

    In neutrophils, activation of the β2-adrenergic receptor (β2AR), a Gs-coupled receptor, inhibits inflammatory responses, which could be therapeutically exploited. The aim of this study was to evaluate the effects of various β2AR ligands on adenosine-3′,5′-cyclic monophosphate (cAMP) accumulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion (O2•−) production in human neutrophils and to probe the concept of ligand-specific receptor conformations (also referred to as functional selectivity or biased signaling) in a native cell system. This is an important question because so far, evidence for functional selectivity has been predominantly obtained with recombinant systems, due to the inherent difficulties to genetically manipulate human native cells. cAMP concentration was determined by HPLC/tandem mass spectrometry, and O2•− formation was assessed by superoxide dismutase-inhibitable reduction of ferricytochrome c. β2AR agonists were generally more potent in inhibiting fMLP-induced O2•− production than in stimulating cAMP accumulation. (−)-Ephedrine and dichloroisoproterenol were devoid of any agonistic activity in the cAMP assay, but partially inhibited fMLP-induced O2•− production. Moreover, (−)-adrenaline was equi-efficacious in both assays whereas the efficacy of salbutamol was more than two-fold higher in the O2•− assay. Functional selectivity was visualized by deviations of ligand potencies and efficacies from linear correlations for various parameters. We obtained no evidence for involvement of protein kinase A in the inhibition of fMLP-induced O2•− production after β2AR-stimulation although cAMP-increasing substances inhibited O2•− production. Taken together, our data corroborate the concept of ligand-specific receptor conformations with unique signaling capabilities in native human cells and suggest that the β2AR inhibits O2•− production in a cAMP-independent manner. PMID

  1. Wild-type and mutant D-xylose isomerase from Actinoplanes missouriensis: metal-ion dissociation constants, kinetic parameters of deuterated and non-deuterated substrates and solvent-isotope effects.

    PubMed Central

    van Bastelaere, P B; Kersters-Hilderson, H L; Lambeir, A M

    1995-01-01

    The metal-ion dissociation constants (Mg2+, Mn2+) of wild-type and mutant D-xylose isomerases from Actinoplanes missouriensis have been determined by titrating the metal-ion-free enzymes with Mg2+ and Mn2+ respectively. Substitution of amino acids co-ordinated to metal-ion 1 (E181D, D245N) dramatically affects the dissociation constants, pH-activity profiles and apparent substrate binding. Mutagenesis of groups ligated to metal-ion 2 is less drastic except for that of Asp-255: a decrease in metal-ion affinity, a change in metal-ion preference and an improved apparent substrate binding (at pH values above the optimum), especially in the presence of Mn2+, are observed for the D255N enzyme. Similar effects, except for a slightly increased metal-ion affinity, are obtained by mutagenesis of the adjacent Glu-186 to Gln and the unconserved Ala-25 to Lys. Moreover, the striking acidic-pH shifts observed for the D255N and E186Q enzymes support the crucial role of the water molecule, Wa-690, Asp-255 and the adjacent Glu-186 in proton transfer from 2-OH to O-1 of the open and extended aldose substrate. Mutations of other important groups scarcely affect the metal-ion dissociation constants and pH-activity profiles, although pronounced effects on the kinetic parameters may be observed. PMID:7717967

  2. Kinetic determinants of agonist action at the recombinant human glycine receptor

    PubMed Central

    Lewis, Trevor M; Schofield, Peter R; McClellan, Annette M L

    2003-01-01

    The amino acids glycine, β-alanine and taurine are all endogenous agonists of the glycine receptor. In this study, a combination of rapid agonist application onto macropatches and steady-state single-channel recordings was used to compare the actions of glycine, β-alanine and taurine upon homomeric α1 human glycine receptors transiently expressed in human embryonic kidney (HEK 293) cells. The 10–90 % rise times determined from rapid application of 100 μm of each agonist were indistinguishable, indicating each agonist has a similar association rate. At saturating concentrations (30 mm) the rise time for glycine (0.26 ms) was 1.8-fold faster than that for β-alanine (0.47 ms) and 3.9-fold faster than that for taurine (1.01 ms), indicating clear differences in the maximum opening rate between agonists. The relaxation following rapid removal of agonist was fitted with a single exponential for β-alanine (3.0 ms) and taurine (2.2 ms), and two exponential components for glycine with a weighted mean time constant of 27.1 ms. This was consistent with differences in dissociation rates estimated from analysis of bursts, with taurine > β-alanine > glycine. Exponential fits to the open period distributions gave time constants that did not differ between agonists and the geometric distribution for the number of openings per burst indicated that all three agonists had a significant component of single-opening bursts. Based upon these data, we propose a kinetic scheme with three independent open states, where the opening rates are dependent upon the activating agonist, while the closing rates are an intrinsic characteristic of the receptor. PMID:12679369

  3. Predicting pressure-dependent unimolecular rate constants using variational transition state theory with multidimensional tunneling combined with system-specific quantum RRK theory: a definitive test for fluoroform dissociation.

    PubMed

    Bao, Junwei Lucas; Zhang, Xin; Truhlar, Donald G

    2016-06-22

    Understanding the falloff in rate constants of gas-phase unimolecular reaction rate constants as the pressure is lowered is a fundamental problem in chemical kinetics, with practical importance for combustion, atmospheric chemistry, and essentially all gas-phase reaction mechanisms. In the present work, we use our recently developed system-specific quantum RRK theory, calibrated by canonical variational transition state theory with small-curvature tunneling, combined with the Lindemann-Hinshelwood mechanism, to model the dissociation reaction of fluoroform (CHF3), which provides a definitive test for falloff modeling. Our predicted pressure-dependent thermal rate constants are in excellent agreement with experimental values over a wide range of pressures and temperatures. The present validation of our methodology, which is able to include variational transition state effects, multidimensional tunneling based on the directly calculated potential energy surface along the tunneling path, and torsional and other vibrational anharmonicity, together with state-of-the-art reaction-path-based direct dynamics calculations, is important because the method is less empirical than models routinely used for generating full mechanisms, while also being simpler in key respects than full master equation treatments and the full reduced falloff curve and modified strong collision methods of Troe. PMID:27273734

  4. The high-spin cytochrome o' component of the cytochrome bo-type quinol oxidase in membranes from Escherichia coli: formation of the primary oxygenated species at low temperatures is characterized by a slow 'on' rate and low dissociation constant.

    PubMed

    Poole, R K; Salmon, I; Chance, B

    1994-05-01

    Cytochromes b and o in membrane vesicles from aerobically grown Escherichia coli were readily reduced by succinate; one cytochrome, which we propose should be called cytochrome o', reacted with CO in the Fe(II) state to give a photodissociable CO adduct. The photodissociation spectrum (photolysed minus pre-photolysis) at sub-zero temperatures had a relatively high gamma/alpha absorbance ratio, indicating a high-spin haem, which, in the reduced state, probably contributes little to the sharp alpha absorbance of the oxidase complex in membranes. Reaction with oxygen of the unliganded high-spin haem between -132 degrees C and -95 degrees C following photolytic activation gave a product that is identified as the oxygenated form, being spectrally similar to, but not identical with, the CO adduct. In membranes, the forward velocity constant at -95 degrees C was 61 M-1s-1, and the dissociation constant was 1.6 x 10(-5) M O2, as it is in intact cells. These data clearly distinguish the oxygen-trapping strategy of the cytochrome o' in this oxidase from that of cytochrome a3 and also suggest that the presence of the soluble flavohaemoglobin (Hmp) in intact cells is without effect on such measurements of the primary oxygen reaction. In view of recent findings that this oxidase complex contains predominantly one mole of haem O and one of haem B, a revised nomenclature for the oxidase complex is proposed, namely, cytochrome bo'. PMID:8025668

  5. Characterization of agonist radioligand interactions with porcine atrial A1 adenosine receptors

    SciTech Connect

    Leid, M.; Schimerlik, M.I.; Murray, T.F.

    1988-09-01

    The agonist radioligand (-)-N6-(125I)-p-hydroxyphenylisopropyl-adenosine (( 125I)HPIA) was used to characterize adenosine recognition sites in porcine atrial membranes. (125I)HPIA showed saturable binding to an apparently homogeneous population of sites with a maximum binding capacity of 35 +/- 3 fmol/mg of protein and an equilibrium dissociation constant of 2.5 +/- 0.4 nM. Kinetic experiments were performed to address the molecular mechanism of (125I)HPIA binding in porcine atrial membranes. (125I)HPIA apparently interacts with the cardiac adenosine receptor in a simple bimolecular reaction. A kinetically derived (125I) HPIA dissociation constant (2.4 nM) was in good agreement with that parameter measured at equilibrium. Guanyl nucleotides negatively modulated (125I)HPIA binding by increasing its rate of dissociation. This finding is consonant with the formation of a ternary complex in porcine atrial membranes, consisting of ligand, receptor, and guanyl nucleotide-binding protein. Prototypic adenosine receptor agonists and antagonists inhibited specific binding in a manner consistent with the labeling of an A1 adenosine receptor. The results of these experiments suggest that the adenosine receptor present in porcine atrial membranes, as labeled by (125I)HPIA, is of the A1 subtype.

  6. Spondylopelvic dissociation.

    PubMed

    Sullivan, Matthew P; Smith, Harvey E; Schuster, James M; Donegan, Derek; Mehta, Samir; Ahn, Jaimo

    2014-01-01

    Spondylopelvic dissociation is a complex injury pattern resulting in multiplanar instability of the lumbopelvis. These injuries have traditionally been known as "suicide jumper's fractures" and have recently increased in prevalence as a result of under-vehicle explosions seen in the past decade of military conflicts in the Middle East. The hallmarks of spondylopelvic dissociation are bilateral vertical sacral fractures with a horizontal component, resulting in lumbosacral instability in the sagittal and axial planes. Surgical treatment has evolved greatly and both percutaneous and open options are available, with triangular osteosynthesis being the most relied on method of fixation. PMID:24267208

  7. Km as an Apparent Dissociation Constant.

    ERIC Educational Resources Information Center

    Cohlberg, Jeffrey A.

    1979-01-01

    An approach to enzyme kinetics which emphasizes similarities between equilibrium binding and steady state kinetics is outlined. It is intended for use in teaching biochemistry to beginning students. (Author/SA)

  8. Mechanism of electrocatalytic hydrogen production by a di-iron model of iron-iron hydrogenase: a density functional theory study of proton dissociation constants and electrode reduction potentials.

    PubMed

    Surawatanawong, Panida; Tye, Jesse W; Darensbourg, Marcetta Y; Hall, Michael B

    2010-03-28

    Simple dinuclear iron dithiolates such as (mu-SCH2CH2CH2S)[Fe(CO)3]2, (1) and (mu-SCH2CH2S)[Fe(CO)3]2 (2) are functional models for diiron-hydrogenases, [FeFe]-H2ases, that catalyze the reduction of protons to H2. The mechanism of H2 production with 2 as the catalyst and with both toluenesulfonic (HOTs) and acetic (HOAc) acids as the H+ source in CH3CN solvent has been examined by density functional theory (DFT). Proton dissociation constants (pKa) and electrode reduction potentials (E(o)) are directly computed and compared to the measured pKa of HOTs and HOAc acids and the experimental reduction potentials. Computations show that when the strong acid, HOTs, is used as a proton source the one-electron reduced species 2- can be protonated to form a bridging hydride complex as the most stable structure. Then, this species can be reduced and protonated to form dihydrogen and regenerate 2. This cycle produces H2 via an ECEC process at an applied potential of -1.8 V vs. Fc/Fc+. A second faster process opens for this system when the species produced at the ECEC step above is further reduced and H2 release returns the system to 2- rather than 2, an E[CECE] process. On the other hand, when the weak acid, HOAc, is the proton source a more negative applied reduction potential (-2.2 V vs. Fc/Fc+) is necessary. At this potential two one-electron reductions yield the dianion 2(2-) before the first protonation, which in this case occurs on the thiolate. Subsequent reduction and protonation form dihydrogen and regenerate 2- through an E[ECEC] process. PMID:20221544

  9. Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists.

    PubMed

    Gilmore, John L; Sheppeck, James E; Wang, Jim; Dhar, T G Murali; Cavallaro, Cullen; Doweyko, Arthur M; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Nadler, Steven G; Dodd, John H; Somerville, John E; Barrish, Joel C

    2013-10-01

    SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. PMID:23916594

  10. Recurrent Episodes of Dissociative Fugue

    PubMed Central

    Angothu, Hareesh; Pabbathi, Lokeswar Reddy

    2016-01-01

    Dissociative fugue is rare entity to encounter with possible differentials of epilepsy and malingering. It is one of the dissociative disorders rarely seen in clinical practice more often because of the short lasting nature of this condition. This might also be because of organized travel of the individuals during the episodes and return to their families after the recovery from episodes. This is a case description of a patient who has experienced total three episodes of dissociative fugue. The patient has presented during the third episode and two prior episodes were diagnosed as fugue episodes retrospectively based on the history. Planned travel in this case by the patient to a distant location was prevented because of early diagnosis and constant vigilance till the recovery. As in this case, it may be more likely that persons with Dissociative fugue may develop similar episodes if they encounter exceptional perceived stress. However, such conclusions may require follow-up studies. PMID:27114633

  11. Interaction of a radiolabeled agonist with cardiac muscarinic cholinergic receptors

    SciTech Connect

    Harden, T.K.; Meeker, R.B.; Martin, M.W.

    1983-12-01

    The interaction of a radiolabeled muscarinic cholinergic receptor agonist, (methyl-/sup 3/H)oxotremorine acetate ((/sup 3/H)OXO), with a washed membrane preparation derived from rat heart, has been studied. In binding assays at 4 degrees C, the rate constants for association and dissociation of (/sup 3/H)OXO were 2 X 10(7) M-1 min-1 and 5 X 10(-3) min-1, respectively, Saturation binding isotherms indicated that binding was to a single population of sites with a Kd of approximately 300 pM. The density of (/sup 3/H)OXO binding sites (90-100 fmol/mg of protein) was approximately 75% of that determined for the radiolabeled receptor antagonist (/sup 3/H)quinuclidinyl benzilate. Both muscarinic receptor agonists and antagonists inhibited the binding of (/sup 3/H)OXO with high affinity and Hill slopes of approximately one. Guanine nucleotides completely inhibited the binding of (/sup 3/H)OXO. This effect was on the maximum binding (Bmax) of (/sup 3/H)OXO with no change occurring in the Kd; the order of potency for five nucleotides was guanosine 5'-O-(3-thio-triphosphate) greater than 5'-guanylylimidodiphosphate greater than GTP greater than or equal to guanosine/diphosphate greater than GMP. The (/sup 3/H)OXO-induced interaction of muscarinic receptors with a guanine nucleotide binding protein was stable to solubilization. That is, membrane receptors that were prelabeled with (/sup 3/H)OXO could be solubilized with digitonin, and the addition of guanine nucleotides to the soluble, (/sup 3/H)OXO-labeled complex resulted in dissociation of (/sup 3/H)OXO from the receptor. Pretreatment of membranes with relatively low concentrations of N-ethylmaleimide inhibited (/sup 3/H)OXO binding by 85% with no change in the Kd of (/sup 3/H)OXO, and with no effect on (/sup 3/H)quinuclidinyl benzilate binding.

  12. Discovery of potent and selective nonsteroidal indazolyl amide glucocorticoid receptor agonists.

    PubMed

    Sheppeck, James E; Gilmore, John L; Xiao, Hai-Yun; Dhar, T G Murali; Nirschl, David; Doweyko, Arthur M; Sack, Jack S; Corbett, Martin J; Malley, Mary F; Gougoutas, Jack Z; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Dodd, John H; Nadler, Steven G; Somerville, John E; Barrish, Joel C

    2013-10-01

    Modification of a phenolic lead structure based on lessons learned from increasing the potency of steroidal glucocorticoid agonists lead to the discovery of exceptionally potent, nonsteroidal, indazole GR agonists. SAR was developed to achieve good selectivity against other nuclear hormone receptors with the ultimate goal of achieving a dissociated GR agonist as measured by human in vitro assays. The specific interactions by which this class of compounds inhibits GR was elucidated by solving an X-ray co-crystal structure. PMID:23953070

  13. Dissociated Vertical Deviation

    MedlinePlus

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Dissociated Vertical Deviation En Español Read in Chinese What is Dissociated Vertical Deviation (DVD)? DVD is ...

  14. Dissociative recombination of molecular ions in the He-Ne plasma. Partial rate constants of atoms formation in the 2 p 53d and 2 p 54d configurations

    NASA Astrophysics Data System (ADS)

    Ivanov, V. A.; Petrovskaya, A. S.; Skoblo, Yu. E.

    2016-02-01

    A spectroscopic study of population processes was carried out for states of the neon atom of the 2 p 53 d configuration in the discharge afterglow in helium with a small admixture of neon ([Ne]/[He] ≈ 10-5) at a pressure of 38 Torr. Based on the comparative analysis of time dependences of the spectral line intensities of the Ne I 2 p 53 d → 2 p 53 d and 2 p 54 d → 2 p 53 d transitions and ratio of ion densities [Ne 2 + ]/[HeNe+], it has been found that the formation of excited Ne(2 p 53 d) atoms in the afterglow caused by two dissociative recombination processes: HeNe+ + e → Ne(2 p 53 d) + Ne and Ne 2 + + e → Ne(2 p 53 d) + Ne. Distributions of population fluxes of the 2 p 53 d levels Γ _{3{d_t}}^{HeN{e^ + }} and Γ _{3{d_t}}^{Ne_2^ + }—were obtained for each of these processes.

  15. Dissociation of gadolinium chelates in mice: relationship to chemical characteristics.

    PubMed

    Wedeking, P; Kumar, K; Tweedle, M F

    1992-01-01

    Tissue distributions of seven 153Gd-labeled Gd chelates were determined at five residence intervals (5 min to 14 days) following intravenous administration of 0.4 mmol/kg to mice. Relationships were sought among physicochemical parameters: thermodynamic and conditional (pH 7.4) equilibrium stability constants (log K and log K'), acid dissociation rate constants (k(obs)), lipophilicity (log P), overall charge, and size (molecular weight). Size and lipophilicity did not correlate with tissue distributions. There were possible correlations between anionic charge and rapid, early renal excretion and between stability constants and long-term residual Gd deposition. Strong correlations (r greater than 0.99) were found between acid dissociation rates and long-term deposition of Gd in the whole body, liver, and femur. This is attributed to dissociation of Gd from the chelates in vivo. Acid dissociation rates may be useful in predicting dissociation of Gd from chelates in vivo. PMID:1501535

  16. Zero-Point Energy Constraint for Unimolecular Dissociation Reactions. Giving Trajectories Multiple Chances To Dissociate Correctly.

    PubMed

    Paul, Amit K; Hase, William L

    2016-01-28

    A zero-point energy (ZPE) constraint model is proposed for classical trajectory simulations of unimolecular decomposition and applied to CH4* → H + CH3 decomposition. With this model trajectories are not allowed to dissociate unless they have ZPE in the CH3 product. If not, they are returned to the CH4* region of phase space and, if necessary, given additional opportunities to dissociate with ZPE. The lifetime for dissociation of an individual trajectory is the time it takes to dissociate with ZPE in CH3, including multiple possible returns to CH4*. With this ZPE constraint the dissociation of CH4* is exponential in time as expected for intrinsic RRKM dynamics and the resulting rate constant is in good agreement with the harmonic quantum value of RRKM theory. In contrast, a model that discards trajectories without ZPE in the reaction products gives a CH4* → H + CH3 rate constant that agrees with the classical and not quantum RRKM value. The rate constant for the purely classical simulation indicates that anharmonicity may be important and the rate constant from the ZPE constrained classical trajectory simulation may not represent the complete anharmonicity of the RRKM quantum dynamics. The ZPE constraint model proposed here is compared with previous models for restricting ZPE flow in intramolecular dynamics, and connecting product and reactant/product quantum energy levels in chemical dynamics simulations. PMID:26738691

  17. Swirling flow of a dissociated gas

    NASA Technical Reports Server (NTRS)

    Wolfram, W. R., Jr.; Walker, W. F.

    1975-01-01

    Most physical applications of the swirling flow, defined as a vortex superimposed on an axial flow in the nozzle, involve high temperatures and the possibility of real gas effects. The generalized one-dimensional swirling flow in a converging-diverging nozzle is analyzed for equilibrium and frozen dissociation using the ideal dissociating gas model. Numerical results are provided to illustrate the major effects and to compare with results obtained for a perfect gas with constant ratio of specific heats. It is found that, even in the case of real gases, perfect gas calculations can give a good estimate of the reduction in mass flow due to swirl.

  18. The dissociative bond.

    PubMed

    Gordon, Nirit

    2013-01-01

    Dissociation leaves a psychic void and a lingering sense of psychic absence. How do 2 people bond while they are both suffering from dissociation? The author explores the notion of a dissociative bond that occurs in the aftermath of trauma--a bond that holds at its core an understanding and shared detachment from the self. Such a bond is confined to unspoken terms that are established in the relational unconscious. The author proposes understanding the dissociative bond as a transitional space that may not lead to full integration of dissociated knowledge yet offers some healing. This is exemplified by R. Prince's (2009) clinical case study. A relational perspective is adopted, focusing on the intersubjective aspects of a dyadic relationship. In the dissociative bond, recognition of the need to experience mutual dissociation can accommodate a psychic state that yearns for relationship when the psyche cannot fully confront past wounds. Such a bond speaks to the need to reestablish a sense of human relatedness and connection when both parties in the relationship suffer from disconnection. This bond is bound to a silence that becomes both a means of protection against the horror of traumatic memory and a way to convey unspoken gestures toward the other. PMID:23282044

  19. Electrophysiological studies in cultured mouse CNS neurones of the actions of an agonist and an inverse agonist at the benzodiazepine receptor.

    PubMed Central

    Jensen, M. S.; Lambert, J. D.

    1986-01-01

    The action of agents which bind with the benzodiazepine (BZ) receptor has been investigated by use of intracellular recordings from dissociated mouse neurones grown in tissue culture. The agents tested were midazolam (an agonist at the BZ receptor) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM-an inverse agonist at the BZ receptor). These were applied to the neurone under study by one of the following methods: iontophoresis; pressure application of known concentrations from blunt pipettes; directly in the perfusing medium. On only very few occasions did midazolam or DMCM have a direct effect on the membrane potential (EM) or conductance (GM) of the impaled neurone. For the neurones where direct effects were present, there was no consistent pattern of response. Neither substance affected the threshold for action potential generation. The effect of midazolam and DMCM on responses evoked by iontophoretic application of gamma-aminobutyric acid (GABA) was also investigated. Three parameters were used to quantify GABA responses: the depolarization (VGABA); the increase in GM (gGABA) measured with constant current pulses; using voltage clamp, the GABA current (IGABA). The GABA response should be quantified by a parameter which is linearly related to the number of GABA-operated channels which are conducting at any instant. VGABA does not fulfil this criterion. gGABA is an appropriate parameter, but is difficult to determine for large responses where the membrane is nearly short circuited. IGABA measured during voltage clamp fulfils this criterion. Midazolam (greater than 10(-6) M) reliably potentiated GABA responses with a parallel shift to the left of the dose-response curve. This is in agreement with biochemical studies where BZs increase the affinity of the GABA receptor for its ligand. The effect of DMCM on GABA responses was more variable. In the majority of cases GABA responses were reduced by DMCM. The threshold dose for this depression was

  20. Beta-Adrenergic Agonists

    PubMed Central

    Barisione, Giovanni; Baroffio, Michele; Crimi, Emanuele; Brusasco, Vito

    2010-01-01

    Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised.

  1. Dissociation of diatomic gases

    NASA Technical Reports Server (NTRS)

    Hansen, C. F.

    1991-01-01

    The Landau-Zener theory of reactive cross sections has been applied to diatomic molecules dissociating from a ladder of rotational and vibrational states. Although the preexponential factor of the Arrhenius rate expression is shown to be a complex function of the dimensionless activation energy, the average over all states in the ladder is well represented by a single factor that varies about as T exp (-n), where the coefficient n is the order of unity. This relation agrees very well with experimental data for dissociation of O2 and N2, for example. The results validate previous empirical assignment of a single preexponential factor in the Arrhenius expression and justify the extrapolation of the expression well beyond the range of data. The theory is then used to calculate the effect of vibrational nonequilibrium on dissociation rate. For Morse oscillators the results are about the same as for harmonic oscillators, and the dissociation from a ladder of equilibrium rotational and nonequilibrium vibrational states is close to an analytic approximation provided by Hammerling, Kivel, and Teare for harmonic oscillators all dissociating from the ground rotational state.

  2. Sustained wash-resistant receptor activation responses of GPR119 agonists.

    PubMed

    Hothersall, J Daniel; Bussey, Charlotte E; Brown, Alastair J; Scott, James S; Dale, Ian; Rawlins, Philip

    2015-09-01

    G protein-coupled receptor 119 (GPR119) is involved in regulating metabolic homoeostasis, with GPR119 agonists targeted for the treatment of type-2 diabetes and obesity. Using the endogenous agonist oleoylethanolamide and a number of small molecule synthetic agonists we have investigated the temporal dynamics of receptor signalling. Using both a dynamic luminescence biosensor-based assay and an endpoint cAMP accumulation assay we show that agonist-driven desensitization is not a major regulatory mechanism for GPR119 despite robust activation responses, regardless of the agonist used. Temporal analysis of the cAMP responses demonstrated sustained signalling resistant to washout for some, but not all of the agonists tested. Further analysis indicated that the sustained effects of one synthetic agonist AR-231,453 were consistent with a role for slow dissociation kinetics. In contrast, the sustained responses to MBX-2982 and AZ1 appeared to involve membrane deposition. We also detect wash-resistant responses to AR-231,453 at the level of physiologically relevant responses in an endogenous expression system (GLP-1 secretion in GLUTag cells). In conclusion, our findings indicate that in a recombinant expression system GPR119 activation is sustained, with little evidence of pronounced receptor desensitization, and for some ligands persistent agonist responses continue despite removal of excess agonist. This provides novel understanding of the temporal responses profiles of potential drug candidates targetting GPR119, and highlights the importance of carefully examining the the mechanisms through which GPCRs generate sustained responses. PMID:26101059

  3. Dissociative Reactions to Incest.

    ERIC Educational Resources Information Center

    Hall, J. Mark

    In contrast to Freud's later and revised view of the etiology of hysterical, or dissociative, symptoms, it is now known that real, and not fantasized, sexual experiences in childhood are experienced in disociative symptomatology. It is useful to understand that incest involves both traumatic events, that is, incidents of sexual violation per se,…

  4. Dissociative Identity Disorder

    ERIC Educational Resources Information Center

    Schmidt, Tom

    2007-01-01

    Few psychological disorders in the Diagnostic Statistical Manual have generated as much controversy as Dissociative Identity Disorder (DID). For the past 35 years diagnoses of DID, previously referred to as Multiple Personality Disorder (MPD), have increased exponentially, causing various psychological researchers and clinicians to question the…

  5. Dissociation and psychosis in dissociative identity disorder and schizophrenia.

    PubMed

    Laddis, Andreas; Dell, Paul F

    2012-01-01

    Dissociative symptoms, first-rank symptoms of schizophrenia, and delusions were assessed in 40 schizophrenia patients and 40 dissociative identity disorder (DID) patients with the Multidimensional Inventory of Dissociation (MID). Schizophrenia patients were diagnosed with the Structured Clinical Interview for the DSM-IV Axis I Disorders; DID patients were diagnosed with the Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised. DID patients obtained significantly (a) higher dissociation scores; (b) higher passive-influence scores (first-rank symptoms); and (c) higher scores on scales that measure child voices, angry voices, persecutory voices, voices arguing, and voices commenting. Schizophrenia patients obtained significantly higher delusion scores than did DID patients. What is odd is that the dissociation scores of schizophrenia patients were unrelated to their reports of childhood maltreatment. Multiple regression analyses indicated that 81% of the variance in DID patients' dissociation scores was predicted by the MID's Ego-Alien Experiences Scale, whereas 92% of the variance in schizophrenia patients' dissociation scores was predicted by the MID's Voices Scale. We propose that schizophrenia patients' responses to the MID do not index the same pathology as do the responses of DID patients. We argue that neither phenomenological definitions of dissociation nor the current generation of dissociation instruments (which are uniformly phenomenological in nature) can distinguish between the dissociative phenomena of DID and what we suspect are just the dissociation-like phenomena of schizophrenia. PMID:22651674

  6. Pathological Dissociation as Measured by the Child Dissociative Checklist

    ERIC Educational Resources Information Center

    Wherry, Jeffrey N.; Neil, Debra A.; Taylor, Tamara N.

    2009-01-01

    The component structure of the Child Dissociative Checklist was examined among abused children. A factor described as pathological dissociation emerged that was predicted by participants being male. There also were differences in pathological dissociation between groups of sexually abused and physically abused children. Replication of this factor…

  7. Kinetic ion thermometers for electron transfer dissociation.

    PubMed

    Pepin, Robert; Tureček, František

    2015-02-19

    Peptide fragment ions of the z-type were used as kinetic ion thermometers to gauge the internal energy of peptide cation-radicals produced by electron transfer in the gas-phase. Electron transfer dissociation (ETD)-produced z2 ions containing the leucine residue, z2(Leu-Lys) and z2(Leu-Arg), were found to undergo spontaneous dissociation by loss of C3H7 that was monitored by time-resolved kinetic measurements on the time scale of the linear ion trap mass spectrometer. Kinetic modeling of the dissociations, including collisional cooling and product loss by neutralization, provided unimolecular rate constants for dissociation that were converted to the z ion internal energies using RRKM theory. The internal energy of z2(Leu-Lys) and z2(Leu-Arg) fragment ions was found to decrease with the increasing size of the precursor peptide ion, indicating vibrational energy partitioning between the ion and neutral fragments and ergodic behavior. The experimentally determined excitation in the peptide cation-radicals upon electron transfer (285-327 kJ mol(-1)) was found to be lower than that theoretically calculated from the reaction exothermicity. The reasons for this missing energy are discussed. PMID:25594857

  8. Three dimensions of dissociative amnesia.

    PubMed

    Dell, Paul F

    2013-01-01

    Principal axis factor analysis with promax rotation extracted 3 factors from the 42 memory and amnesia items of the Multidimensional Inventory of Dissociation (MID) database (N = 2,569): Discovering Dissociated Actions, Lapses of Recent Memory and Skills, and Gaps in Remote Memory. The 3 factors' shared variance ranged from 36% to 64%. Construed as scales, the 3 factor scales had Cronbach's alpha coefficients of .96, .94, and .93, respectively. The scales correlated strongly with mean Dissociative Experiences Scale scores, mean MID scores, and total scores on the Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised (SCID-D-R). What is interesting is that the 3 amnesia factors exhibited a range of correlations with SCID-D-R Amnesia scores (.52, .63, and .70, respectively), suggesting that the SCID-D-R Amnesia score emphasizes gaps in remote memory over amnesias related to dissociative identity disorder. The 3 amnesia factor scales exhibited a clinically meaningful pattern of significant differences among dissociative identity disorder, dissociative disorder not otherwise specified-1, dissociative amnesia, depersonalization disorder, and nonclinical participants. The 3 amnesia factors may have greater clinical utility for frontline clinicians than (a) amnesia as discussed in the context of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, nosology of the dissociative disorders or (b) P. Janet's (1893/1977 ) 4-fold classification of dissociative amnesia. The author recommends systematic study of the phenomenological differences within specific dissociative symptoms and their differential relationship to specific dissociative disorders. PMID:23282045

  9. Dissociation and psychotic symptoms.

    PubMed

    Steingard, S; Frankel, F H

    1985-08-01

    The literature on hysterical or brief reactive psychosis reflects great diversity both in clinical description and theoretical formulation. The authors describe the case of a 17-year-old girl who presented with a diagnosis of bipolar affective disorder, rapid cycling type, but who, in fact, was experiencing dissociative episodes manifested as psychotic states. The patient's successful treatment with hypnosis is described, along with the clinical and theoretical implications of the case. PMID:4025593

  10. A theoretical study on ascorbic acid dissociation in water clusters.

    PubMed

    Demianenko, Eugeniy; Ilchenko, Mykola; Grebenyuk, Anatoliy; Lobanov, Victor; Tsendra, Oksana

    2014-03-01

    Dissociation of ascorbic acid in water has been studied by using a cluster model. It was examined by density functional theory (DFT) with the В3LYP, M06, and wB97XD functionals and a 6-311++G(d,p) basis set. The thermodynamic and kinetic characteristics of proton transfer from ascorbic acid molecule to water clusters were calculated as well as the equilibrium constants (pK a ) for the related processes. The used functionals in the DFT method together with continuum solvent models provided results close to the experimental data for the dissociation constant of ascorbic acid in aqueous solution. PMID:24567154

  11. Experimental Dissociation of Methane Hydrates Through Depressurization

    NASA Astrophysics Data System (ADS)

    Borgfeldt, T.; Flemings, P. B.; Meyer, D.; You, K.

    2015-12-01

    We dissociated methane hydrates by stepwise depressurization. The initial hydrates were formed by injecting gas into a cylindrical sample of brine-saturated, coarse-grained sand at hydrate-stable conditions with the intention of reaching three-phase equilibrium. The sample was initially at 1°C with a pore pressure of 1775 psi and a salinity of 7 wt. % NaBr. The depressurization setup consisted of one pump filled with tap water attached to the confining fluid port and a second pump attached to the inlet port where the methane was injected. Depressurization was conducted over sixteen hours at a constant temperature of 1°C. The pore pressure was stepwise reduced from 1775 psi to atmospheric pressure by pulling known volumes of gas from the sample. After each extraction, we recorded the instantaneous and equilibrium pore pressure. 0.503 moles of methane were removed from the sample. The pore pressure decreased smoothly and nonlinearly with the cumulative gas withdrawn from the sample. We interpret that hydrate began to dissociate immediately with depressurization, and it continued to dissociate when the pressure decreased below the three-phase pressure for 1°C and 0 wt. % salinity. Two breaks in slope in the pressure vs. mass extracted data are bounded by smooth, nonlinear curves with differing slopes on either side. We attribute the breaks to dissociation of three zones of hydrate concentration. We created a box model to simulate the experimental behavior. For a 10% initial gas saturation (estimated from the hydrate formation experiment and based on mass conservation), an initial hydrate saturation of 55% is required to match the total methane extracted from the sample. Future experiments will be conducted over a longer timespan while monitoring hydrate dissociation with CT imaging throughout the process.

  12. Relationships of agonist properties to the single channel kinetics of nicotinic acetylcholine receptors.

    PubMed Central

    Papke, R L; Millhauser, G; Lieberman, Z; Oswald, R E

    1988-01-01

    The effects of the systematic variations of the acetylcholine molecule on the microscopic kinetics of channel activation were studied using the patch clamp technique. The modifications consisted of adding either halogens or a methyl group to the acetyl carbon of acetylcholine, which results in a change in both the steric and ionic character of that portion of the molecule. The ionic character of the bond affected both the opening and closing rates of the channel. An increase in the ionicity decreased the opening rate and increased the closing rate of the channel, suggesting that the open state was destabilized. Increasing the size of the substituent decreased both the association and dissociation rates for agonist binding but had little effect on the equilibrium constant. This indicates that the energy barrier for binding and unbinding was increased without a major change in the energy of the bound and unbound states. These results suggest that it is possible to assign changes in the structural characteristics of the ligand to changes in individual steps in a reaction scheme, which can lead to specific predictions for the properties of related compounds. PMID:2449251

  13. a Measurement of the Homogeneous Rate of Thermal Dissociation of Uranium Hexafluoride by Shock Tube Densitometry

    NASA Astrophysics Data System (ADS)

    Scoles, Stephen Wesley

    1990-01-01

    A determination of the rate of homogeneous thermal dissociation of UF_6 is reported. The high temperature region of a shock tube generated flow was used to dissociate UF_6. Laser -schlieren diagnostic techniques were used to measure post -shock density gradient and shock wave velocity, from which the dissociation rate constant and post-shock conditions were determined. The unimolecular dissociation theory of Rice, Ramsparger, and Kassel was used to model the temperature - and density-dependent rate constants. When extrapolated to the high density limit the dissociation rate constant obtained is:rm k_infty = 3.51times 10^{13}{bf e}^{{-64.6+/-6.3 {kcal over mole}over R_{U}T }}{1over sec}.This result agrees with a reliable theoretical calculation by another investigator, but differs by two orders of magnitude from the only other experimental measurements in the open literature.

  14. Recurrent dissociative fugue.

    PubMed

    Mamarde, Abhishek; Navkhare, Praveen; Singam, Amrita; Kanoje, Akash

    2013-10-01

    Dissociative fugue is a rarely reported diagnostic entity. It is one of the least understood and yet clinically one of the most fascinating disorders in mental health. Here, we describe a case of fugue in a 32-year-old man who was brought to mental hospital with complete loss of memory for events pertaining to identity of self. This case illustrates the nature of presentation in hospital setting like mental hospital and effort taken to reintegrate his identity and reunite with his family. PMID:24379504

  15. Energetics from Slow Infrared Multiphoton Dissociation of Biomolecules

    PubMed Central

    Jockusch, Rebecca A.; Paech, Kolja

    2005-01-01

    Photodissociation kinetics of the protonated pentapeptide leucine enkephalin measured using a cw CO2 laser and a Fourier-transform mass spectrometer are reported. A short induction period, corresponding to the time required to raise the internal energy of the ion population to a (dissociating) steady state, is observed. After this induction period, the dissociation data are accurately fit by first-order kinetics. A plot of the log of the unimolecular dissociation rate constant, kuni, as a function of the log of laser power is linear at low laser powers (<9 W, kuni <0.05 s−1), but tapers off at high laser power (9–33 W, kuni = 0.05–7 s−1). The entire measured dissociation curve can be accurately fit by an exponential function plus a constant. The experiment is simulated using a master equation formalism. In the model, the laser radiation is described as an energetically flat-topped distribution which is spatially uniform. This description is consistent with experimental results which indicate that ion motion within the cell averages out spatial inhomogeneities in the laser light. The model has several adjustable parameters. The effect of varying these parameters on the calculated kinetics and power dependence curves is discussed. A procedure for determining a limited range of threshold dissociation energy, Eo, which fits both the measured induction period and power dependence curves, is presented. Using this procedure, Eo of leucine enkephalin is determined to be 1.12–1.46 eV. This result is consistent with, although less precise than, values measured previously using blackbody infrared radiative dissociation. Although the blackbody dissociation results were used as a starting point to search for fits of the master equation model to experiment, these results demonstrate that it is, in principle, possible to determine a limited range of Eo from slow infrared multiphoton dissociation data alone. PMID:16467893

  16. THE DISSOCIATIVE TURN IN PSYCHOANALYSIS.

    PubMed

    Itzkowitz, Sheldon

    2015-06-01

    In his response to the Roundtable Discussions on what is effective in psychoanalytic psychotherapy, the author focuses on the renewed interest in the concept of dissociation that began to emerge toward the end of the 20th century. A contemporary psychoanalytic position informed by the impact of developmental trauma has led to an understanding of and interest in the dissociative mind. The actuality of trauma during infancy and early childhood is recognized as a key factor leading to the emergence of dissociative processes, the potential dissociative structuring of the mind, and mind being characterized by multiple, discontinuous, centers of consciousness. The therapeutic goal in the psychoanalytic work with fragmented patients is to establish communication and understanding between the dissociated self-states. The author offers two brief clinical examples of working with dissociated self-states. PMID:26177756

  17. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.

    PubMed

    DeVree, Brian T; Mahoney, Jacob P; Vélez-Ruiz, Gisselle A; Rasmussen, Soren G F; Kuszak, Adam J; Edwald, Elin; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A; Pardon, Els; Steyaert, Jan; Kobilka, Brian K; Sunahara, Roger K

    2016-07-01

    G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the β2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID:27362234

  18. Dissociative Electron Attachment

    NASA Astrophysics Data System (ADS)

    Arreola, Esmeralda; Esmeralda Arreola Collaboration; Leigh Hargreaves Collaboration

    Since the pioneering work of Boudiaffa et al., it has been understood that electrons, even with energies near or below the ionization threshold, are capable of initiating strand-breaks in human DNA. This discovery raised important questions for cancer treatments, since sub-ionizing electrons are known to be the most copiously produced secondary product of radiation therapy. But even to date these factors are largely excluded from dosimetry calculations. This lack of inclusion is, at least in part, certainly due to the dearth of fundamental data describing low-energy electron interactions with nucleotide molecules that form the basis of DNA. Understanding of how such slow electrons are able to damage DNA remains incomplete, but the strongly peaked nature of Boudiaffa et al.'s data gives strong hints at resonantly driven collision processes. DNA damage is therefore most likely driven by ``dissociative electron attachment'' (DEA). DEA is a rather complicated process to model due to the coupling of electronic and nuclear degrees of freedom in the molecule. At the California State University Fullerton, we are currently commissioning a new spectrometer to study dissociation channels, reaction rates and orientation effects in DEA collisions between slow electrons and nucleotide molecules. At the meeting we will present design parameters and commissioning data for this new apparatus.

  19. Hyperglycemia associated dissociative fugue (organic dissociative disorder) in an elderly

    PubMed Central

    Ram, Dushad; Ashoka, H. G; Gowdappa, Basavnna

    2015-01-01

    Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed. PMID:26286620

  20. Dissociative States and Neural Complexity

    ERIC Educational Resources Information Center

    Bob, Petr; Svetlak, Miroslav

    2011-01-01

    Recent findings indicate that neural mechanisms of consciousness are related to integration of distributed neural assemblies. This neural integration is particularly vulnerable to past stressful experiences that can lead to disintegration and dissociation of consciousness. These findings suggest that dissociation could be described as a level of…

  1. Agonist-trafficking and hallucinogens.

    PubMed

    González-Maeso, Javier; Sealfon, Stuart C

    2009-01-01

    Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT(2A) receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs. PMID:19275609

  2. Dissociative absorption: An empirically unique, clinically relevant, dissociative factor.

    PubMed

    Soffer-Dudek, Nirit; Lassri, Dana; Soffer-Dudek, Nir; Shahar, Golan

    2015-11-01

    Research of dissociative absorption has raised two questions: (a) Is absorption a unique dissociative factor within a three-factor structure, or a part of one general dissociative factor? Even when three factors are found, the specificity of the absorption factor is questionable. (b) Is absorption implicated in psychopathology? Although commonly viewed as "non-clinical" dissociation, absorption was recently hypothesized to be specifically associated with obsessive-compulsive symptoms. To address these questions, we conducted exploratory and confirmatory factor analyses on 679 undergraduates. Analyses supported the three-factor model, and a "purified" absorption scale was extracted from the original inclusive absorption factor. The purified scale predicted several psychopathology scales. As hypothesized, absorption was a stronger predictor of obsessive-compulsive symptoms than of general psychopathology. In addition, absorption was the only dissociative scale that longitudinally predicted obsessive-compulsive symptoms. We conclude that absorption is a unique and clinically relevant dissociative tendency that is particularly meaningful to obsessive-compulsive symptoms. PMID:26241024

  3. The association-dissociation behavior of the ApoE proteins: kinetic and equilibrium studies

    PubMed Central

    Garai, Kanchan; Frieden, Carl

    2010-01-01

    The apolipoprotein E family consists of three major protein isoforms: apolipoprotein E4 (ApoE4), ApoE3 and ApoE2. The isoforms, which contain 299 residues, differ only by single amino acid changes but of the three only ApoE4 is a risk factor for Alzheimer’s Disease. At μM concentrations lipid-free ApoE exists predominantly as tetramers. In more dilute solutions, lower molecular weight species predominate. Using Fluorescence Correlation Spectroscopy (FCS), intermolecular Fluorescence Resonance Energy Transfer (FRET) and sedimentation methods we find that the association-dissociation reaction of ApoE can be modeled with a monomer-dimer-tetramer process. Equilibrium constants have been determined from the sedimentation data while the individual rate constants for association and dissociation are determined by measuring the kinetics of dissociation of ApoE and are in agreement with the equilibrium constants. Dissociation kinetics as measured by intermolecular FRET show two phases reflecting the dissociation of tetramer to dimer and of dimer to monomer with dissociation from tetramer to dimer being more rapid than the dimer to monomer dissociation. The rate constants differ for the different ApoE isoforms showing that the association-dissociation process is isoforms specific. Strikingly, the association rate constants are almost two orders of magnitude slower than expected for a diffusion controlled process. Dissociation kinetics were also monitored by tryptophan fluorescence in presence of acrylamide and the data found to be consistent with the monomer-dimer-tetramer model. The approach combining multiple methods establishes the reaction scheme of ApoE self-association. PMID:20923231

  4. Somatostatin binding to dissociated cells from rat cerebral cortex

    SciTech Connect

    Colas, B.; Prieto, J.C.; Arilla, E. )

    1990-11-01

    A method has been developed for the study of somatostatin (SS) binding to dissociated cells from rat cerebral cortex. Binding of {sup 125}I (Tyr11)SS to cells obtained by mechanical dissociation of rat cerebral cortex was dependent on time and temperature, saturable, reversible and highly specific. Under conditions of equilibrium, i.e., 60 min at 25 degrees C, native SS inhibited tracer binding in a dose-dependent manner. The Scatchard analysis of binding data was linear and yielded a dissociation constant of 0.60 +/- 0.08 nM with a maximal binding capacity of 160 +/- 16 fmol/mg protein. The binding of {sup 125}I (Tyr11)SS was specific as shown in experiments on tracer displacement by the native peptides, SS analogues, and unrelated peptides.

  5. Agonist binding and function at the human alpha(2A)-adrenoceptor: allosteric modulation by amilorides.

    PubMed

    Leppik, R A; Birdsall, N J

    2000-11-01

    It has been found previously that amilorides act via an allosteric site on the alpha(2A)-adrenergic receptor to strongly inhibit antagonist binding. In this study, allosteric modulation of agonist binding and function at the alpha(2A)-adrenergic receptor was explored. The dissociation rate of the agonist [(3)H]UK14304 from alpha(2A)-receptors was decreased by the amilorides in a concentration-dependent manner. This contrasts with the increases in (3)H-antagonist dissociation rate found previously. The agonist-amiloride analog interaction data could be fitted to equations derived from the ternary complex allosteric model. The calculated log affinities of the amilorides at the [(3)H]UK14304-occupied receptor increased with the size of the 5-N-alkyl side chain and ranged from 2.4 for amiloride to 4.2 for 5-(N,N-hexamethylene)-amiloride. The calculated negative cooperativities cover a narrow range, in sharp contrast to the broad range found for antagonist-amiloride analog interactions. The effects of the amilorides on the agonist actions of UK14304, epinephrine, and norepinephrine were explored using a [(35)S]GTPgammaS functional assay, and the parameters calculated for the cooperativities and affinities of the UK14304-amiloride analog interactions, using the equation derived from the ternary complex allosteric model, were in good agreement with those derived from the kinetic studies. Therefore both the binding and functional data provide further support for the existence of a well defined allosteric site on the human alpha(2A)-adrenergic receptor. The binding mode of the amilorides at the agonist-occupied and antagonist-occupied receptor differs markedly but, within each group, the structure of either the agonist or the antagonist examined has only a slight effect on the allosteric interactions. PMID:11040058

  6. Dissociative disorders in DSM-5.

    PubMed

    Spiegel, David; Lewis-Fernández, Roberto; Lanius, Ruth; Vermetten, Eric; Simeon, Daphne; Friedman, Matthew

    2013-01-01

    The rationale, research literature, and proposed changes to the dissociative disorders and conversion disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are presented. Dissociative identity disorder will include reference to possession as well as identity fragmentation, to make the disorder more applicable to culturally diverse situations. Dissociative amnesia will include dissociative fugue as a subtype, since fugue is a rare disorder that always involves amnesia but does not always include confused wandering or loss of personality identity. Depersonalization disorder will include derealization as well, since the two often co-occur. A dissociative subtype of posttraumatic stress disorder (PTSD), defined by the presence of depersonalization or derealization in addition to other PTSD symptoms, is being recommended, based upon new epidemiological and neuroimaging evidence linking it to an early life history of adversity and a combination of frontal activation and limbic inhibition. Conversion disorder (functional neurological symptom disorder) will likely remain with the somatic symptom disorders, despite considerable dissociative comorbidity. PMID:23394228

  7. Activation of endplate nicotinic acetylcholine receptors by agonists.

    PubMed

    Auerbach, Anthony

    2015-10-15

    The interaction of a small molecule made in one cell with a large receptor made in another is the signature event of cell signaling. Understanding the structure and energy changes associated with agonist activation is important for engineering drugs, receptors and synapses. The nicotinic acetylcholine receptor (AChR) is a ∼300kD ion channel that binds the neurotransmitter acetylcholine (ACh) and other cholinergic agonists to elicit electrical responses in the central and peripheral nervous systems. This mini-review is in two sections. First, general concepts of skeletal muscle AChR operation are discussed in terms of energy landscapes for conformational change. Second, adult vs. fetal AChRs are compared with regard to interaction energies between ACh and agonist-site side chains, measured by single-channel electrophysiology and molecular dynamics simulations. The five aromatic residues that form the core of each agonist binding site can be divided into two working groups, a triad (led by αY190) that behaves similarly at all sites and a coupled pair (led by γW55) that has a large influence on affinity only in fetal AChRs. Each endplate AChR has 5 homologous subunits, two of α(1) and one each of β, δ, and either γ (fetal) or ϵ (adult). These nicotinic AChRs have only 2 functional agonist binding sites located in the extracellular domain, at αδ and either αγ or αϵ subunit interfaces. The receptor undergoes a reversible, global isomerization between structures called C and O. The C shape does not conduct ions and has a relatively low affinity for ACh, whereas O conducts cations and has a higher affinity. When both agonist sites are empty (filled only with water) the probability of taking on the O conformation (PO) is low, <10(-6). When ACh molecules occupy the agonist sites the C→O opening rate constant and C↔O gating equilibrium constant increase dramatically. Following a pulse of ACh at the nerve-muscle synapse, the endplate current rises rapidly

  8. Global functioning and disability in dissociative disorders.

    PubMed

    Mueller-Pfeiffer, Christoph; Rufibach, Kaspar; Perron, Noelle; Wyss, Daniela; Kuenzler, Cornelia; Prezewowsky, Cornelia; Pitman, Roger K; Rufer, Michael

    2012-12-30

    Dissociative disorders are frequent comorbid conditions of other mental disorders. Yet, there is controversy about their clinical relevance, and little systematic research has been done on how they influence global functioning. Outpatients and day care patients (N=160) of several psychiatric units in Switzerland were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders, Structured Clinical Interview for DSM-IV Dissociative Disorders, Global Assessment of Functioning Scale, and World Health Organization Disability Assessment Schedule-II. The association between subjects with a dissociative disorder (N=30) and functional impairment after accounting for non-dissociative axis I disorders was evaluated by linear regression models. We found a proportion of 18.8% dissociative disorders (dissociative amnesia=0%, dissociative fugue=0.6%, depersonalization disorder=4.4%, dissociative identity disorder=7.5%, dissociative disorder-not-otherwise-specified=6.3%) across treatment settings. Adjusted for other axis I disorders, subjects with a comorbid dissociative identity disorder or dissociative disorder-not-otherwise-specified had a median global assessment of functioning score that was 0.86 and 0.88 times, respectively, the score of subjects without a comorbid dissociative disorder. These findings support the hypothesis that complex dissociative disorders, i.e., dissociative identity disorder and dissociative disorder-not-otherwise-specified, contribute to functional impairment above and beyond the impact of co-existing non-dissociative axis I disorders, and that they qualify as "serious mental illness". PMID:22578820

  9. Dissociative experiences and dissociative minds: Exploring a nomological network of dissociative functioning.

    PubMed

    Schimmenti, Adriano

    2016-01-01

    In this study, the psychometric properties of the Dissociative Experiences Scale-II (DES-II) were tested in a sample of Italian adults, and a nomological network of dissociative functioning based on current psychodynamic research was examined. A total of 794 participants (55% females) ranging in age from 18 to 64 completed the DES-II and other measures of theory of mind, alexithymia, attachment style, and empathy. The Italian translation of the DES-II showed high internal consistency, adequate item-to-scale homogeneity, and good split-half reliability. A single-factor solution including the 8 items of pathological dissociation (DES-T) adequately fit the data. Participants who reported higher levels of dissociative experiences showed significantly lower scores on theory of mind and empathy than other participants. They also showed significantly higher scores on alexithymia, preoccupied attachment, and fearful attachment. Results of the study support the view that people who suffer from severe dissociative experiences may also have difficulties mentalizing and regulating affects and that they may feel uncomfortable in close relationships because they have a negative view of the self. This can inform clinical work with dissociative individuals, who could benefit from therapies that consider their potential problems with mentalization, empathy, affect regulation, and attachment. PMID:26507547

  10. Visuomotor Dissociation in Cerebral Scaling of Size.

    PubMed

    Potgieser, Adriaan R E; de Jong, Bauke M

    2016-01-01

    Estimating size and distance is crucial in effective visuomotor control. The concept of an internal coordinate system implies that visual and motor size parameters are scaled onto a common template. To dissociate perceptual and motor components in such scaling, we performed an fMRI experiment in which 16 right-handed subjects copied geometric figures while the result of drawing remained out of sight. Either the size of the example figure varied while maintaining a constant size of drawing (visual incongruity) or the size of the examples remained constant while subjects were instructed to make changes in size (motor incongruity). These incongruent were compared to congruent conditions. Statistical Parametric Mapping (SPM8) revealed brain activations related to size incongruity in the dorsolateral prefrontal and inferior parietal cortex, pre-SMA / anterior cingulate and anterior insula, dominant in the right hemisphere. This pattern represented simultaneous use of a 'resized' virtual template and actual picture information requiring spatial working memory, early-stage attention shifting and inhibitory control. Activations were strongest in motor incongruity while right pre-dorsal premotor activation specifically occurred in this condition. Visual incongruity additionally relied on a ventral visual pathway. Left ventral premotor activation occurred in all variably sized drawing while constant visuomotor size, compared to congruent size variation, uniquely activated the lateral occipital cortex additional to superior parietal regions. These results highlight size as a fundamental parameter in both general hand movement and movement guided by objects perceived in the context of surrounding 3D space. PMID:26963705

  11. Visuomotor Dissociation in Cerebral Scaling of Size

    PubMed Central

    Potgieser, Adriaan R. E.; de Jong, Bauke M.

    2016-01-01

    Estimating size and distance is crucial in effective visuomotor control. The concept of an internal coordinate system implies that visual and motor size parameters are scaled onto a common template. To dissociate perceptual and motor components in such scaling, we performed an fMRI experiment in which 16 right-handed subjects copied geometric figures while the result of drawing remained out of sight. Either the size of the example figure varied while maintaining a constant size of drawing (visual incongruity) or the size of the examples remained constant while subjects were instructed to make changes in size (motor incongruity). These incongruent were compared to congruent conditions. Statistical Parametric Mapping (SPM8) revealed brain activations related to size incongruity in the dorsolateral prefrontal and inferior parietal cortex, pre-SMA / anterior cingulate and anterior insula, dominant in the right hemisphere. This pattern represented simultaneous use of a ‘resized’ virtual template and actual picture information requiring spatial working memory, early-stage attention shifting and inhibitory control. Activations were strongest in motor incongruity while right pre-dorsal premotor activation specifically occurred in this condition. Visual incongruity additionally relied on a ventral visual pathway. Left ventral premotor activation occurred in all variably sized drawing while constant visuomotor size, compared to congruent size variation, uniquely activated the lateral occipital cortex additional to superior parietal regions. These results highlight size as a fundamental parameter in both general hand movement and movement guided by objects perceived in the context of surrounding 3D space. PMID:26963705

  12. Dissociative symptomatology in cancer patients

    PubMed Central

    Civilotti, Cristina; Castelli, Lorys; Binaschi, Luca; Cussino, Martina; Tesio, Valentina; Di Fini, Giulia; Veglia, Fabio; Torta, Riccardo

    2015-01-01

    Introduction: The utilization of the post-traumatic stress disorder (PTSD) diagnostic spectrum is currently being debated to categorize psychological adjustment in cancer patients. The aims of this study were to: (1) evaluate the presence of cancer-related traumatic dissociative symptomatology in a sample of cancer patients; (2) examine the correlation of cancer-related dissociation and sociodemographic and medical variables, anxiety, depression, and post-traumatic stress symptomatology; (3) investigate the predictors of cancer-related dissociation. Methods: Ninety-two mixed cancer patients (mean age: 58.94, ds = 10.13) recruited from two hospitals in northern Italy were administered a questionnaire on sociodemographic and medical characteristics, the Karnofsky Scale to measure the level of patient activity and medical care requirements, the Hospital Anxiety and Depression Scale (HADS) to evaluate the presence of anxiety and depression, the Impact of Event Scale Revised (IES-R) to assess the severity of intrusion, avoidance, and hypervigilance, and the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) to quantify the traumatic dissociative symptomatology. Results: 31.5% of participants report a PDEQ score above the cutoff. The results indicated that dissociative symptomatology was positively correlated with HADS scores (HADS-Anxiety: r = 0.476, p < 0.001; HADS-Depression: r = 0.364, p < 0.001) and with IES-R scores (IES-R-Intrusion: r = 0.698, p < 0.001; IES-R-Avoidance: r = 0.619, p < 0.001; IES-R- Hypervigilance: r = 0.681, p < 0.001). A stepwise regression analysis was performed in order to find the predictors of cancer-related traumatic dissociative symptomatology. The results converged on a three predictor model revealing that IES-R-Intrusion, IES-R-Avoidance, and IES-R-Hyperarousal accounted for 53.9% of the explained variance. Conclusion: These findings allow us to hypothesize a specific psychological reaction which may be ascribed to the traumatic

  13. Acetylated histone H3 increases nucleosome dissociation

    NASA Astrophysics Data System (ADS)

    Simon, Marek; Manohar, Mridula; Ottesen, Jennifer; Poirier, Michael

    2009-03-01

    Chromatin's basic unit structure is the nucleosome, i.e. genomic DNA wrapped around a particular class of proteins -- histones -- which due to their physical hindrance, block vital biological processes, such as DNA repair, DNA replication, and RNA transcription. Histone post-translational modifications, which are known to exist in vivo, are hypothesized to regulate these biological processes by directly altering DNA-histone interactions and thus nucleosome structure and stability. Using magnetic tweezers technique we studied the acetylation of histone H3 in the dyad region, i.e. at K115 and K122, on reconstituted arrays of nucleosomes under constant external force. Based on the measured increase in the probability of dissociation of modified nucleosomes, we infer that this double modification could facilitate histone chaperone mediated nucleosome disassembly in vivo.

  14. Some remarks on the selection of exit channels in the theoretical description of dissociative recombination

    NASA Astrophysics Data System (ADS)

    Guberman, Steven L.

    2015-01-01

    The need for the careful selection of dissociative routes for inclusion in the theoretical calculation of accurate dissociative recombination (DR) cross sections and rate constants is discussed. For total energies corresponding to the sum of the "free" electron energy plus the ion vibrational energy, all neutral diabatic curves that fall between or near the turning points of the highest Rydberg vibrational levels with the same electronic symmetry need to be included in the calculation. This is especially the case if there are several dissociative routes of the same electronic symmetry that satisfy this criterion. Also, care must be exercised in the exclusion of dissociative routes having relatively small electron capture widths. Examples from theoretical studies of the dissociative recombination (DR) of N2+ are used as illustrations.

  15. Diffraction dissociation at the LHC

    NASA Astrophysics Data System (ADS)

    Jenkovszky, László; Orava, Risto; Salii, Andrii

    2013-04-01

    We report on recent calculations of low missing mass single (SD) and double (DD) diffractive dissociation at LHC energies. The calculations are based on a dual-Regge model, dominated by a single Pomeron exchange. The diffractively excited states lie on the nucleon trajectory N*, appended by the isolated Roper resonance. Detailed predictions for the squared momentum transfer and missing mass dependence of the differential and integrated single-and double diffraction dissociation in the kinematical range of present and future LHC measurements are given.

  16. Diffraction dissociation at the LHC

    SciTech Connect

    Jenkovszky, Laszlo; Orava, Risto; Salii, Andrii

    2013-04-15

    We report on recent calculations of low missing mass single (SD) and double (DD) diffractive dissociation at LHC energies. The calculations are based on a dual-Regge model, dominated by a single Pomeron exchange. The diffractively excited states lie on the nucleon trajectory N*, appended by the isolated Roper resonance. Detailed predictions for the squared momentum transfer and missing mass dependence of the differential and integrated single-and double diffraction dissociation in the kinematical range of present and future LHC measurements are given.

  17. Dissociation of pleasure in psychopathology.

    PubMed

    Brown, S L

    1981-01-01

    This paper analyzes the development of the concept of dissociation from 19th century psychological theory through 20th century neurophysiological thought. Recent research is discussed, indicating that normal individuals show an "association" between emitted pleasurable behavior and self-perception of pleasurable activity, whereas depressives and schizophrenics show a lack of association, or "dissociation," between these measures. concomitantly, depressives show an abnormal degree of association between the experience and expression of negative affect. Such a discrepancy in systems of affect is considered as both an important pathological element in mental disorder and also as a valuable new research tool for studying etiology, differential diagnosis, and therapeutic efficacy in psychobiological illness. PMID:7005394

  18. Clinical use of GnRH agonists in canine and feline species.

    PubMed

    Fontaine, E; Fontbonne, A

    2011-04-01

    GnRH (gonadotrophin releasing hormone) is a key hormone of reproductive function in mammals; agonist forms have been largely developed, and data concerning their use in small animal reproduction are now abundant. GnRH agonists act by a two-step mechanism. First, their agonist properties on the pituitary will cause marked LH (luteinizing hormone) and FSH (follicle-stimulating hormone) secretion into the bloodstream, accompanied by an increase in the concentrations of sex steroid hormones. Then, in case of constant administration, GnRH agonists will lead to pituitary desensitization, and FSH and LH levels will collapse. These two effects have been widely documented, and these compounds have many potential benefits in a clinical context, capitalizing both on their stimulating and sterilizing effects. PMID:20964727

  19. K+ efflux agonists induce NLRP3 inflammasome activation independently of Ca2+ signaling1

    PubMed Central

    Katsnelson, Michael A.; Rucker, L. Graham; Russo, Hana M.; Dubyak, George R.

    2015-01-01

    Perturbation of intracellular ion homeostasis is a major cellular stress signal for activation of NLRP3 inflammasome signaling that results in caspase-1 mediated production of IL-1β and pyroptosis. However, the relative contributions of decreased cytosolic [K+] versus increased cytosolic [Ca2+] remain disputed and incompletely defined. We investigated roles for elevated cytosolic [Ca2+] in NLRP3 activation and downstream inflammasome signaling responses in primary murine dendritic cells and macrophages in response to two canonical NLRP3 agonists (ATP and nigericin) that facilitate primary K+ efflux by mechanistically distinct pathways or the lysosome-destabilizing agonist Leu-Leu-O-methyl ester (LLME). The study provides three major findings relevant to this unresolved area of NLRP3 regulation. First, increased cytosolic [Ca2+] was neither a necessary nor sufficient signal for the NLRP3 inflammasome cascade during activation by endogenous ATP-gated P2X7 receptor channels, the exogenous bacterial ionophore nigericin, or the lysosomotropic agent LLME. Second, agonists for three Ca2+-mobilizing G protein-coupled receptors (formyl peptide receptor/FPR; P2Y2 purinergic receptor/P2Y2R; calcium-sensing receptor/CaSR) expressed in murine dendritic cells were ineffective as activators of rapidly induced NLRP3 signaling when directly compared to the K+ efflux agonists. Third, the intracellular Ca2+ buffer, BAPTA, and the channel blocker, 2-aminoethoxydiphenyl borate (2-APB), widely used reagents for disruption of Ca2+-dependent signaling pathways, strongly suppressed nigericin-induced NLRP3 inflammasome signaling via mechanisms dissociated from their canonical or expected effects on Ca2+ homeostasis. The results indicate that the ability of K+ efflux agonists to activate NLRP3 inflammasome signaling can be dissociated from changes in cytosolic [Ca2+] as a necessary or sufficient signal. PMID:25762778

  20. Defining Nicotinic Agonist Binding Surfaces through Photoaffinity Labeling†

    PubMed Central

    Tomizawa, Motohiro; Maltby, David; Medzihradszky, Katalin F.; Zhang, Nanjing; Durkin, Kathleen A.; Presley, Jack; Talley, Todd T.; Taylor, Palmer; Burlingame, Alma L.; Casida, John E.

    2016-01-01

    Nicotinic acetylcholine (ACh) receptor (nAChR) agonists are potential therapeutic agents for neurological dysfunction. In the present study, the homopentameric mollusk ACh binding protein (AChBP), used as a surrogate for the extracellular ligand-binding domain of the nAChR, was specifically derivatized by the highly potent agonist azidoepibatidine (AzEPI) prepared as a photoaffinity probe and radioligand. One EPI-nitrene photoactivated molecule was incorporated in each subunit interface binding site based on analysis of the intact derivatized protein. Tryptic fragments of the modified AChBP were analyzed by collision-induced dissociation and Edman sequencing of radiolabeled peptides. Each specific EPI-nitrene-modified site involved either Tyr195 of loop C on the principal or (+)-face or Met116 of loop E on the complementary or (−)-face. The two derivatization sites were observed in similar frequency, providing evidence of the reactivity of the azido/nitrene probe substituent and close proximity to both residues. [3H]AzEPI binds to the α4β2 nAChR at a single high-affinity site and photoaffinity-labels only the α4 subunit, presumably modifying Tyr225 spatially corresponding to Tyr195 of AChBP. Phe137 of the β2 nAChR subunit, equivalent to Met116 of AChBP, conceivably lacks sufficient reactivity with the nitrene generated from the probe. The present photoaffinity labeling in a physiologically relevant condition combined with the crystal structure of AChBP allows development of precise structural models for the AzEPI interactions with AChBP and α4β2 nAChR. These findings enabled us to use AChBP as a structural surrogate to define the nAChR agonist site. PMID:17614369

  1. [Gender differences in dissociative disorders].

    PubMed

    Spitzer, C; Freyberger, H J

    2008-01-01

    The relationship between mental illness, on the one hand, and sex and gender, on the other hand, has received interest since the beginning of medicine in antique times. A prototypical example of a seemingly woman-specific disease is hysteria. The term itself, which is derived from the Greek word for womb, denotes a psychosexual dimension comprising the current attitude towards sexuality and the dominating gender relationship. In addition, the colourful history of hysteria indicates that illness is not exclusively determined by biological factors, but also significantly by socio-cultural influences, for example in the treatment of hysterical women. Even nowadays, there is a wide-spread belief that dissociative symptoms and disorders, which have succeeded hysteria in current classification systems, are predominantly seen in women. However, empirical studies in the general population and in different clinical samples using sound instruments have indicated that dissociative symptoms do not differ between the genders. The seemingly dominance of dissociative disorders in women may also depend on the socio-cultural context, because men with dissociative disorders usually do not enter the general health system, but rather the legal system, i.e. they can be found in jail or forensic institutions. PMID:18185968

  2. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

  3. Two-temperature models for nitrogen dissociation

    NASA Astrophysics Data System (ADS)

    da Silva, M. Lino; Guerra, V.; Loureiro, J.

    2007-12-01

    Accurate sets of nitrogen state-resolved dissociation rates have been reduced to two-temperature (translational T and vibrational Tv) dissociation rates. The analysis of such two-temperature dissociation rates shows evidence of two different dissociation behaviors. For Tv < 0.3 T dissociation proceeds predominantly from the lower-lying vibrational levels, whereas for Tv > 0.3 T dissociation proceeds predominantly form the near-dissociative vibrational levels, with an abrupt change of behavior at Tv = 0.3 T. These two-temperature sets have then been utilized as a benchmark for the comparison against popular multitemperature dissociation models (Park, Hansen, Marrone-Treanor, Hammerling, Losev-Shatalov, Gordiets, Kuznetsov, and Macheret-Fridman). This has allowed verifying the accuracy of each theoretical model, and additionally proposing adequate values for any semi-empirical parameters present in the different theories. The Macheret-Fridman model, who acknowledges the existence of the two aforementioned dissociation regimes, has been found to provide significantly more accurate results than the other models. Although these different theoretical approaches have been tested and validated solely for nitrogen dissociation processes, it is reasonable to expect that the general conclusions of this work, regarding the adequacy of the different dissociation models, could be extended to the description of arbitrary diatomic dissociation processes.

  4. Study of the dissociation of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Vessot, R. F. C.

    1981-01-01

    Dissociators used to obtain an RF plasma discharge for hydrogen masers and the test system used for operation and evaluation of the dissociators are described. A compact sorption cartridge using a graphite matrix is tested as part of a hydrogen scavenging system. Testing of a vacuum enclosed hydrogen dissociator suitable for long term operation in space is described.

  5. Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo.

    PubMed

    Vayssière, B M; Dupont, S; Choquart, A; Petit, F; Garcia, T; Marchandeau, C; Gronemeyer, H; Resche-Rigon, M

    1997-08-01

    Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids. However, major side effects severely limit their therapeutic use. The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects. One possibility toward this goal is to try to dissociate two main activities of glucocorticoids, i.e. transactivation and transrepression. Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids, which exert strong AP-1 inhibition but little or no transactivation. Importantly, despite high ligand binding affinity, the prototypic dissociated compound, RU24858, acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells. Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene (TAT), which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis. To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids, several in vitro and in vivo models were used. Indeed, secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells. Moreover, in two in vivo models, these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone. These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery. PMID:9259316

  6. On the Khinchin Constant

    NASA Technical Reports Server (NTRS)

    Bailey, David H.; Borwein, Jonathan M.; Crandall, Richard E.; Craw, James M. (Technical Monitor)

    1995-01-01

    We prove known identities for the Khinchin constant and develop new identities for the more general Hoelder mean limits of continued fractions. Any of these constants can be developed as a rapidly converging series involving values of the Riemann zeta function and rational coefficients. Such identities allow for efficient numerical evaluation of the relevant constants. We present free-parameter, optimizable versions of the identities, and report numerical results.

  7. Solar constant secular changes

    NASA Technical Reports Server (NTRS)

    Schatten, Kenneth H.; Orosz, Jerome A.

    1990-01-01

    A recent model for solar constant secular changes is used to calculate a 'proxy' solar constant for: (1) the past four centuries, based upon the sunspot record, (2) the past nine centuries, based upon C-14 observations and their relation to solar activity, and (3) the next decade, based upon a dynamo theory model for the solar cycle. The proxy solar constant data is tabulated as it may be useful for climate modelers studying global climate changes.

  8. Quantitative structure-(chromatographic) retention relationship models for dissociating compounds.

    PubMed

    Kubik, Łukasz; Wiczling, Paweł

    2016-08-01

    The aim of this work was to develop mathematical models relating the hydrophobicity and dissociation constant of an analyte with its structure, which would be useful in predicting analyte retention times in reversed-phase liquid chromatography. For that purpose a large and diverse group of 115 drugs was used to build three QSRR models combining retention-related parameters (logkw-chromatographic measure of hydrophobicity, S-slope factor from Snyder-Soczewinski equation, and pKa) with structural descriptors calculated by means of molecular modeling for both dissociated and nondissociated forms of analytes. Lasso, Stepwise and PLS regressions were used to build statistical models. Moreover a simple QSRR equations based on lipophilicity and dissociation constant parameters calculated in the ACD/Labs software were proposed and compared with quantum chemistry-based QSRR equations. The obtained relationships were further used to predict chromatographic retention times. The predictive performances of the obtained models were assessed using 10-fold cross-validation and external validation. The QSRR equations developed were simple and were characterized by satisfactory predictive performance. Application of quantum chemistry-based and ACD-based descriptors leads to similar accuracy of retention times' prediction. PMID:26960942

  9. p-( sup 125 I)iodoclonidine, a novel radiolabeled agonist for studying central alpha 2-adrenergic receptors

    SciTech Connect

    Baron, B.M.; Siegel, B.W. )

    1990-09-01

    Unlabeled p-iodoclonidine was efficacious in attenuating forskolin-stimulated cAMP accumulation in SK-N-SH neuroblastoma cells. Maximal attenuation was 76 +/- 3%, with an EC50 of 347 +/- 60 nM. Comparable values of epinephrine were 72 +/- 3% and 122 +/- 22 nM. Responses to both agonists were abolished by 10 microM phentolamine. Therefore, p-iodoclonidine is an agonist in a cell culture model system of the neuronal alpha 2-adrenergic receptor. p-(125I)Iodoclonidine binding to membranes were measured using various regions of the rat brain. The agonist labeled a single population of sites present on cerebral cortical membranes, which was saturable (Bmax = 230 fmol/mg of protein) and possessed high affinity for the ligand (Kd = 0.6 nM). Binding was largely specific (93% at 0.6 nM). A variety of alpha 2-adrenergic agonists and antagonists were shown to compete for the binding of the radioligand. The binding of p-(125I)iodoclonidine was much less sensitive to agents that interact with alpha 1-adrenergic, serotonergic, and dopaminergic receptors. Approximately 65% of the binding was sensitive to guanine nucleotides. Association kinetics using 0.4 nM radioligand were biphasic (37% associate rapidly, with kobs = 0.96 min-1, with the remainder binding more slowly, with kobs = 0.031 min-1) and reached a plateau by 90 min at 25 degrees. Dissociation kinetics were also biphasic, with 30% of the binding dissociating rapidly (k1 = 0.32 min-1) and the remainder dissociating 50-fold more slowly (k2 = 0.006 min-1). Agonist binding is, therefore, uniquely complex and probably reflects the conformational changes that accompany receptor activation.

  10. Coulomb dissociation of N,2120

    NASA Astrophysics Data System (ADS)

    Röder, Marko; Adachi, Tatsuya; Aksyutina, Yulia; Alcantara, Juan; Altstadt, Sebastian; Alvarez-Pol, Hector; Ashwood, Nicholas; Atar, Leyla; Aumann, Thomas; Avdeichikov, Vladimir; Barr, M.; Beceiro, Saul; Bemmerer, Daniel; Benlliure, Jose; Bertulani, Carlos; Boretzky, Konstanze; Borge, Maria J. G.; Burgunder, G.; Caamaño, Manuel; Caesar, Christoph; Casarejos, Enrique; Catford, Wilton; Cederkäll, Joakim; Chakraborty, S.; Chartier, Marielle; Chulkov, Leonid; Cortina-Gil, Dolores; Crespo, Raquel; Datta Pramanik, Ushasi; Diaz-Fernandez, Paloma; Dillmann, Iris; Elekes, Zoltan; Enders, Joachim; Ershova, Olga; Estrade, A.; Farinon, F.; Fraile, Luis M.; Freer, Martin; Freudenberger, M.; Fynbo, Hans; Galaviz, Daniel; Geissel, Hans; Gernhäuser, Roman; Göbel, Kathrin; Golubev, Pavel; Gonzalez Diaz, D.; Hagdahl, Julius; Heftrich, Tanja; Heil, Michael; Heine, Marcel; Heinz, Andreas; Henriques, Ana; Holl, Matthias; Ickert, G.; Ignatov, Alexander; Jakobsson, Bo; Johansson, Hâkan; Jonson, Björn; Kalantar-Nayestanaki, Nasser; Kanungo, Rituparna; Kelic-Heil, Aleksandra; Knöbel, Ronja; Kröll, Thorsten; Krücken, Reiner; Kurcewicz, J.; Kurz, Nikolaus; Labiche, Marc; Langer, Christoph; Le Bleis, Tudi; Lemmon, Roy; Lepyoshkina, Olga; Lindberg, Simon; Machado, Jorge; Marganiec, Justyna; Mostazo Caro, Magdalena; Movsesyan, Alina; Najafi, Mohammad Ali; Nilsson, Thomas; Nociforo, Chiara; Panin, Valerii; Paschalis, Stefanos; Perea, Angel; Petri, Marina; Pietri, S.; Plag, Ralf; Prochazka, A.; Rahaman, Md. Anisur; Rastrepina, Ganna; Reifarth, Rene; Ribeiro, Guillermo; Ricciardi, M. Valentina; Rigollet, Catherine; Riisager, Karsten; Rossi, Dominic; Sanchez del Rio Saez, Jose; Savran, Deniz; Scheit, Heiko; Simon, Haik; Sorlin, Olivier; Stoica, V.; Streicher, Branislav; Taylor, Jon; Tengblad, Olof; Terashima, Satoru; Thies, Ronja; Togano, Yasuhiro; Uberseder, Ethan; Van de Walle, J.; Velho, Paulo; Volkov, Vasily; Wagner, Andreas; Wamers, Felix; Weick, Helmut; Weigand, Mario; Wheldon, Carl; Wilson, G.; Wimmer, Christine; Winfield, J. S.; Woods, Philip; Yakorev, Dmitry; Zhukov, Mikhail; Zilges, Andreas; Zuber, Kai; R3B Collaboration

    2016-06-01

    Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N,2120 are reported. Relativistic N,2120 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the 19N (n ,γ )20N and 20N (n ,γ ) 21N excitation functions and thermonuclear reaction rates have been determined. The 19 (n ,γ )20N rate is up to a factor of 5 higher at T <1 GK with respect to previous theoretical calculations, leading to a 10% decrease in the predicted fluorine abundance.

  11. [Prison psychosis and dissociative disorders].

    PubMed

    al Chaabani, S; Bataille, M

    2002-12-01

    Through a few clinical case histories stemming from their daily activities at the psychiatric section of the Lantin Prison, the authors propose to revisit the classic concept of Prison psychosis. They broaden its limits to include other psychotic and dissociative phenomena common to the jail population. This requires a strict differential diagnosis, allowing to eliminate some similar pathologies; nevertheless, some difficulties and imperfections persist. The development of the psychosis, the input from the jail architecture and milieu, the predisposing as well as facilitating factors linked to the personality of the inmate, and triggering phenomena are discussed. Finally, the comorbidity between these psychotic/dissociative phenomena and the borderline & histrionic personality disorders is envisaged. PMID:12632838

  12. [Dis-social personality disorder].

    PubMed

    Habermeyer, E; Herpertz, S C

    2006-05-01

    Deviant behavior is gaining in clinical importance if it is founded on stable, characteristic, and enduring patterns of psychopathologically relevant personality traits which have their onset in childhood or adolescence. The classification of these traits shows variations, so that a distinction between the ICD-10 diagnosis of dis-social personality disorder, DSM-IV diagnosis of antisocial personality disorder, and the concept "psychopathy" is necessary. Our knowledge about the biological basis of antisocial behavior includes neurophysiologic, psychophysiologic, and genetic findings. Also relevant are results of neurotransmitter studies and structural resp. functional neuroimaging findings. Psychosocial risk factors include parental deficits, rejection, disregard, unstable relations, and abuse. Efficient psychotherapeutic treatment is cognitive-behavioral. Pharmacologic treatment is largely "off-label". The diagnosis of antisocial and dis-social personality disorders allows no conclusions on criminal responsibility. In addition to psychiatric diagnostics, considerations on the severity of the disorder and its effects on the ability to inhibit actions are necessary. PMID:16609871

  13. Coupling of disulfide bond and distal histidine dissociation in human ferrous cytoglobin regulates ligand binding.

    PubMed

    Beckerson, Penny; Reeder, Brandon J; Wilson, Michael T

    2015-02-13

    Earlier kinetics studies on cytoglobin did not assign functional properties to specific structural forms. Here, we used defined monomeric and dimeric forms and cysteine mutants to show that an intramolecular disulfide bond (C38-C83) alters the dissociation rate constant of the intrinsic histidine (H81) (∼1000 fold), thus controlling binding of extrinsic ligands. Through time-resolved spectra we have unequivocally assigned CO binding to hexa- and penta-coordinate forms and have made direct measurement of histidine rebinding following photolysis. We present a model that describes how the cysteine redox state of the monomer controls histidine dissociation rate constants and hence extrinsic ligand binding. PMID:25601563

  14. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  15. Fundamental Physical Constants

    National Institute of Standards and Technology Data Gateway

    SRD 121 CODATA Fundamental Physical Constants (Web, free access)   This site, developed in the Physics Laboratory at NIST, addresses three topics: fundamental physical constants, the International System of Units (SI), which is the modern metric system, and expressing the uncertainty of measurement results.

  16. Desensitization of Functional µ-Opioid Receptors Increases Agonist Off-Rate

    PubMed Central

    2014-01-01

    Desensitization of µ-opioid receptors (MORs) develops over 5–15 minutes after the application of some, but not all, opioid agonists and lasts for tens of minutes after agonist removal. The decrease in function is receptor selective (homologous) and could result from 1) a reduction in receptor number or 2) a decrease in receptor coupling. The present investigation used photolysis of two caged opioid ligands to examine the kinetics of MOR-induced potassium conductance before and after MOR desensitization. Photolysis of a caged antagonist, carboxynitroveratryl-naloxone (caged naloxone), blocked the current induced by a series of agonists, and the time constant of decline was significantly decreased after desensitization. The increase in the rate of current decay was not observed after partial blockade of receptors with the irreversible antagonist, β-chlornaltrexamine (β-CNA). The time constant of current decay after desensitization was never more rapid than 1 second, suggesting an increased agonist off-rate rather than an increase in the rate of channel closure downstream of the receptor. The rate of G protein–coupled K+ channel (GIRK) current activation was examined using photolysis of a caged agonist, carboxynitrobenzyl-tyrosine-[Leu5]-enkephalin. After acute desensitization or partial irreversible block of MORs with β-CNA, there was an increase in the time it took to reach a peak current. The decrease in the rate of agonist-induced GIRK conductance was receptor selective and dependent on receptor number. The results indicate that opioid receptor desensitization reduced the number of functional receptor and that the remaining active receptors have a reduced agonist affinity. PMID:24748657

  17. [Clinical Handling of Patients with Dissociative Disorders].

    PubMed

    Okano, Kenichiro

    2015-01-01

    This paper discusses the way informed psychiatrists are expected to handle dissociative patients in clinical situations, with a specific focus on dissociative identity disorders and dissociative fugue. On the initial interview with dissociative patients, information on their history of trauma and any nascent dissociative symptoms in their childhood should be carefully obtained. Their level of stress in their current life should also be assessed in order to understand their symptomatology, as well as to predict their future clinical course. A psychoeducational approach is crucial; it might be helpful to give information on dissociative disorder to these patients as well as their family members in order to promote their adherence to treatment. Regarding the symptomatology of dissociative disorders, detailed symptoms and the general clinical course are presented. It was stressed that dissociative identity disorder and dissociative fugue, the most high-profile dissociative disorders, are essentially different in their etiology and clinical presentation. Dissociative disorders are often confused with and misdiagnosed as psychotic disorders, such as schizophrenia. Other conditions considered in terms of the differential diagnosis include borderline personality disorder as well as temporal lobe epilepsy. Lastly, the therapeutic approach to dissociative identity disorder is discussed. Each dissociative identity should be understood as potentially representing some traumatically stressful event in the past. The therapist should be careful not to excessively promote the creation or elaboration of any dissociative identities. Three stages are proposed in the individual psychotherapeutic process. In the initial stage, a secure environment and stabilization of symptoms should be sought. The second stage consists of aiding the "host" personality to make use of other more adaptive coping skills in their life. The third stage involves coaching as well as continuous awareness of

  18. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  19. STABILITY OF A SPHERICAL ACCRETION SHOCK WITH NUCLEAR DISSOCIATION

    SciTech Connect

    Fernandez, Rodrigo; Thompson, Christopher

    2009-06-01

    We examine the stability of a standing shock wave within a spherical accretion flow onto a gravitating star, in the context of core-collapse supernova explosions. Our focus is on the effect of nuclear dissociation below the shock on the linear growth, and nonlinear saturation, of nonradial oscillations of the shocked fluid. We combine two-dimensional, time-dependent hydrodynamic simulations using FLASH2.5 with a solution to the linear eigenvalue problem, and demonstrate the consistency of the two approaches. Previous studies of this 'standing accretion shock instability' (SASI) have focused either on zero-energy accretion flows without nuclear dissociation, or made use of a detailed finite-temperature nuclear equation of state and included strong neutrino heating. Our main goal in this and subsequent papers is to introduce equations of state of increasing complexity, in order to isolate the various competing effects. In this work, we employ an ideal gas equation of state with a constant rate of nuclear dissociation below the shock, and do not include neutrino heating. We find that a negative Bernoulli parameter below the shock significantly lowers the real frequency, growth rate, and saturation amplitude of the SASI. A decrease in the adiabatic index has similar effects. The nonlinear development of the instability is characterized by an expansion of the shock driven by turbulent kinetic energy at nearly constant internal energy. Our results also provide further insight into the instability mechanism: the rate of growth of a particular mode is fastest when the radial advection time from the shock to the accretor overlaps with the period of a standing lateral sound wave. The fastest-growing mode can therefore be modified by nuclear dissociation.

  20. The influence of porosity and structural parameters on different kinds of gas hydrate dissociation

    PubMed Central

    Misyura, S. Y.

    2016-01-01

    Methane hydrate dissociation at negative temperatures was studied experimentally for different artificial and natural samples, differing by macro- and micro-structural parameters. Four characteristic dissociation types are discussed in the paper. The internal kinetics of artificial granule gas hydrates and clathrate hydrates in coal is dependent on the porosity, defectiveness and gas filtration rate. The density of pores distribution in the crust of formed ice decreases by the several orders of magnitude and this change significantly the rate of decay. Existing models for describing dissociation at negative temperatures do not take into account the structural parameters of samples. The dissociation is regulated by internal physical processes that must be considered in the simulation. Non-isothermal dissociation with constant external heat flux was simulated numerically. The dissociation is simulated with consideration of heat and mass transfer, kinetics of phase transformation and gas filtering through a porous medium of granules for the negative temperatures. It is shown that the gas hydrate dissociation in the presence of mainly microporous structures is fundamentally different from the disintegration of gas hydrates containing meso and macropores. PMID:27445113

  1. The influence of porosity and structural parameters on different kinds of gas hydrate dissociation

    NASA Astrophysics Data System (ADS)

    Misyura, S. Y.

    2016-07-01

    Methane hydrate dissociation at negative temperatures was studied experimentally for different artificial and natural samples, differing by macro- and micro-structural parameters. Four characteristic dissociation types are discussed in the paper. The internal kinetics of artificial granule gas hydrates and clathrate hydrates in coal is dependent on the porosity, defectiveness and gas filtration rate. The density of pores distribution in the crust of formed ice decreases by the several orders of magnitude and this change significantly the rate of decay. Existing models for describing dissociation at negative temperatures do not take into account the structural parameters of samples. The dissociation is regulated by internal physical processes that must be considered in the simulation. Non-isothermal dissociation with constant external heat flux was simulated numerically. The dissociation is simulated with consideration of heat and mass transfer, kinetics of phase transformation and gas filtering through a porous medium of granules for the negative temperatures. It is shown that the gas hydrate dissociation in the presence of mainly microporous structures is fundamentally different from the disintegration of gas hydrates containing meso and macropores.

  2. The influence of porosity and structural parameters on different kinds of gas hydrate dissociation.

    PubMed

    Misyura, S Y

    2016-01-01

    Methane hydrate dissociation at negative temperatures was studied experimentally for different artificial and natural samples, differing by macro- and micro-structural parameters. Four characteristic dissociation types are discussed in the paper. The internal kinetics of artificial granule gas hydrates and clathrate hydrates in coal is dependent on the porosity, defectiveness and gas filtration rate. The density of pores distribution in the crust of formed ice decreases by the several orders of magnitude and this change significantly the rate of decay. Existing models for describing dissociation at negative temperatures do not take into account the structural parameters of samples. The dissociation is regulated by internal physical processes that must be considered in the simulation. Non-isothermal dissociation with constant external heat flux was simulated numerically. The dissociation is simulated with consideration of heat and mass transfer, kinetics of phase transformation and gas filtering through a porous medium of granules for the negative temperatures. It is shown that the gas hydrate dissociation in the presence of mainly microporous structures is fundamentally different from the disintegration of gas hydrates containing meso and macropores. PMID:27445113

  3. The cosmological constant problem

    SciTech Connect

    Dolgov, A.D.

    1989-05-01

    A review of the cosmological term problem is presented. Baby universe model and the compensating field model are discussed. The importance of more accurate data on the Hubble constant and the Universe age is stressed. 18 refs.

  4. Space Shuttle astrodynamical constants

    NASA Technical Reports Server (NTRS)

    Cockrell, B. F.; Williamson, B.

    1978-01-01

    Basic space shuttle astrodynamic constants are reported for use in mission planning and construction of ground and onboard software input loads. The data included here are provided to facilitate the use of consistent numerical values throughout the project.

  5. Constant potential pulse polarography

    USGS Publications Warehouse

    Christie, J.H.; Jackson, L.L.; Osteryoung, R.A.

    1976-01-01

    The new technique of constant potential pulse polarography, In which all pulses are to be the same potential, is presented theoretically and evaluated experimentally. The response obtained is in the form of a faradaic current wave superimposed on a constant capacitative component. Results obtained with a computer-controlled system exhibit a capillary response current similar to that observed In normal pulse polarography. Calibration curves for Pb obtained using a modified commercial pulse polarographic instrument are in good accord with theoretical predictions.

  6. Aspirin metabolites are GPR35 agonists.

    PubMed

    Deng, Huayun; Fang, Ye

    2012-07-01

    Aspirin is widely used as an anti-inflammatory, anti-platelet, anti-pyretic, and cancer-preventive agent; however, the molecular mode of action is unlikely due entirely to the inhibition of cyclooxygenases. Here, we report the agonist activity of several aspirin metabolites at GPR35, a poorly characterized orphan G protein-coupled receptor. 2,3,5-Trihydroxybenzoic acid, an aspirin catabolite, was found to be the most potent GPR35 agonist among aspirin metabolites. Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin. PMID:22526472

  7. Religious Dissociation and Economic Appraisal in Brazil.

    PubMed

    François Dengah, H J

    2016-04-01

    Research on the association between religion and health often neglects to provide an explicit theoretical mechanism of influence between faith and well-being. This research posits that dissociative behaviors, such as glossolalia, may provide a biological pathway that influences both physiological and psychological health. This paper argues that religious dissociation acts as a moderator between economic stressors and psychobiological appraisal. Brazil, with its economic inequality and preponderance of religious dissociative rituals, provides an ideal context to examine religious dissociation as a moderator of stress. Utilizing data from a cross section of Brazilian faiths, this paper examines: (1) Whether individuals with low socioeconomic status preferentially participate and experience religious dissociative states and (2) whether dissociative states are correlated with greater psychological appraisal of status. PMID:25687180

  8. Dissociative Tendencies and Facilitated Emotional Processing

    PubMed Central

    Oathes, Desmond J.; Ray, William J.

    2009-01-01

    Dissociation is a process linked to lapses of attention, history of abuse or trauma, compromised emotional memory, and a disintegrated sense of self. It is theorized that dissociation stems from avoiding emotional information, especially negative emotion, to protect a fragile psyche. The present study tested whether or not dissociaters do actually avoid processing emotion by asking groups scoring high or low on the Dissociative Experiences Scale to judge the affective valence of several types of emotional stimuli. Manipulations of valence, modality (pictures or words), task complexity, and personal relevance lead to results suggesting that dissociation is linked to facilitated rather than deficient emotional processing. Our results are consistent with a theory that sensitivity to emotional material may be a contributing factor in subsequent dissociation to avoid further elaboration of upsetting emotion in these individuals. The findings for dissociation further exemplify the influence of individual differences in the link between cognition and emotion. PMID:18837615

  9. Coulomb Dissociation of 27P

    NASA Astrophysics Data System (ADS)

    Beceiro Novo, S.; Sümmerer, K.; Cortina-Gil, D.; Wimmer, C.; Plag, R.; Alvarez-Pol, H.; Aumann, T.; Behr, K.; Boretzky, K.; Casarejos, E.; Chatillon, A.; Datta-Pramanik, U.; Elekes, Z.; Fulop, Z.; Galaviz, D.; Geissel, H.; Giron, S.; Greife, U.; Hammache, F.; Heil, M.; Hoffman, J.; Johansson, H.; Karagiannis, C.; Kiselev, O.; Kurz, N.; Larsson, K.; Le Bleis, T.; Litvinov, Y.; Mahata, K.; Muentz, C.; Nociforo, C.; Ott, W.; Paschalis, S.; Prokopowicz, W.; Rodriguez-Tajes, C.; Rossi, D.; Simon, H.; Stanoiu, M.; Stroth, J.; Typel, S.; Wagner, A.; Wamers, F.; Weick, H.

    2012-09-01

    In this work the astrophysical 26Si(p,γ)27P reaction is studied using the Coulomb dissociation technique. We performed a 27P Coulomb Dissociation experiment at GSI, Darmstadt (28 May-5 June 2007) using the ALADIN-LAND setup which allows complete-kinematic studies. A secondary 27P beam at 498 AMeV impinging a 515mg/cm2 Pb target was used. The relative energy of the outgoing system (26Si+p) is measured obtaining the resonant states of the 27P. Preliminary results show four resonant states measured at 0.36±0.07, 0.88±0.09, 1.5±0.2, 2.3±0.3 MeV and evidence of a higher state at around 3.1 MeV. The preliminary total cross section obtained for relative energies between 0 and 3 MeV has been measured and yields 55±7 mb.

  10. Dissociative recombination in planetary ionospheres

    NASA Technical Reports Server (NTRS)

    Fox, J. L.

    1993-01-01

    Ionization in planetary atmospheres can be produced by solar photoionization, photoelectron impact ionization, and, in auroral regions, by impact of precipitating particles. This ionization is lost mainly in dissociative recombination (DR) of molecular ions. Although atomic ions cannot undergo DR, they can be transformed locally through ion-molecule reactions into molecular ions, or they may be transported vertically or horizontally to regions of the atmosphere where such transformations are possible. Because DR reactions tend to be very exothermic, they can be an important source of kinetically or internally excited fragments. In interplanetary thermospheres, the neutral densities decrease exponentially with altitude. Below the homopause (or turbopause), the atmosphere is assumed to be throughly mixed by convection and/or turbulence. Above the homopause, diffusion is the major transport mechanism, and each species is distributed according to its mass, with the logarithmic derivative of the density with repect to altitude given approximately by -1/H, where H = kT/mg is the scale height. In this expression, T is the neutral temperature, g is the local acceleratiion of gravity, and m is the mass of the species. Thus lighter species become relatively more abundant, and heavier species less abundant, as the altitude increases. This variation of the neutral composition can lead to changes in the ion composition; furthermore, as the neutral densities decrease, dissociative recombination becomes more important relative to ion-neutral reactions as a loss mechanism for molecular ions.

  11. Dissociation rate of bromine diatomics in an argon heat bath

    NASA Technical Reports Server (NTRS)

    Razner, R.; Hopkins, D.

    1973-01-01

    The evolution of a collection of 300 K bromine diatomics embedded in a heat bath of argon atoms at 1800 K was studied by computer, and a dissociation-rate constant for the reaction Br2 + BR + Ar yields Br + Ar was determined. Previously published probability distributions for energy and angular momentum transfers in classical three-dimensional Br2-Ar collisions were used in conjunction with a newly developed Monte Carlo scheme for this purpose. Results are compared with experimental shock-tube data and the predictions of several other theoretical models. A departure from equilibrium is obtained which is significantly greater than that predicted by any of these other theories.

  12. Monoterpenoid agonists of TRPV3

    PubMed Central

    Vogt-Eisele, A K; Weber, K; Sherkheli, M A; Vielhaber, G; Panten, J; Gisselmann, G; Hatt, H

    2007-01-01

    Background and purpose: Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated. Experimental approach: Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes. Key results: Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC50 is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent. Conclusions and implications: Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement. PMID:17420775

  13. Dissociative Recombination without a Curve Crossing

    NASA Technical Reports Server (NTRS)

    Guberman, Steven L.

    1994-01-01

    Ab initio calculations show that a curve crossing is not always needed for a high dissociative- recombination cross section. For HeH(+), in which no neutral states cross the ion potential curve, dissociative recombination is driven by the nuclear kinetic-energy operator on adiabatic potential curves. The kinetic-energy derivative operator allows for capture into repulsive curves that are outside of the classical turning points for the nuclear motion. The dominant dissociative route is the C (2)Sigma(+) state leading to H(n = 2) atoms. An analogous mechanism is proposed for the dissociative recombination of H3(+).

  14. Degree of somatoform and psychological dissociation in dissociative disorder is correlated with reported trauma.

    PubMed

    Nijenhuis, E R; Spinhoven, P; van Dyck, R; van der Hart, O; Vanderlinden, J

    1998-10-01

    In this study, the prevalence and severity of traumatic experiences as reported by patients with dissociative disorders and with other DSM-IV psychiatric diagnoses were compared. Furthermore, the predictive value of emotional, physical, and sexual trauma with respect to somatoform and psychological dissociation was analyzed. In contrast with comparison patients, dissociative disorder patients reported severe and multifaceted traumatization. Physical and sexual trauma predicted somatoform dissociation, sexual trauma predicted psychological dissociation as well. According to the memories of the dissociative disorder patients, this abuse occurred in an emotionally neglectful and abusive social context. Pathological dissociation was best predicted by early onset of reported intense, chronic and multiple traumatization. Methodological limitations restricting causal inferences between reported trauma and dissociation are discussed. PMID:9870223

  15. Dissociative symptoms and dissociative disorder comorbidity in patients with obsessive-compulsive disorder.

    PubMed

    Belli, Hasan; Ural, Cenk; Vardar, Melek Kanarya; Yesılyurt, Sema; Oncu, Fatıh

    2012-10-01

    The present study attempted to assess the dissociative symptoms and overall dissociative disorder comorbidity in patients with obsessive-compulsive disorder (OCD). In addition, we examined the relationship between the severity of obsessive-compulsive symptoms and dissociative symptoms. All patients admitted for the first time to the psychiatric outpatient unit were included in the study. Seventy-eight patients had been diagnosed as having OCD during the 2-year study period. Patients had to meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD. Most (76.9%; n = 60) of the patients were female, and 23.1% (n = 18) of the patients were male. Dissociation Questionnaire was used to measure dissociative symptoms. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Dissociative Disorders interviews and Yale-Brown Obsessive Compulsive Checklist and Severity Scale were used. Eleven (14%) of the patients with OCD had comorbid dissociative disorder. The most prevalent disorder in our study was dissociative depersonalization disorder. Dissociative amnesia and dissociative identity disorder were common as well. The mean Yale-Brown score was 23.37 ± 7.27 points. Dissociation Questionnaire scores were between 0.40 and 3.87 points, and the mean was 2.23 ± 0.76 points. There was a statistically significant positive correlation between Yale-Brown points and Dissociation Questionnaire points. We conclude that dissociative symptoms among patients with OCD should alert clinicians for the presence of a chronic and complex dissociative disorder. Clinicians may overlook an underlying dissociative process in patients who have severe symptoms of OCD. However, a lack of adequate response to cognitive-behavioral and drug therapy may be a consequence of dissociative process. PMID:22425531

  16. Modeling heating curve for gas hydrate dissociation in porous media.

    PubMed

    Dicharry, Christophe; Gayet, Pascal; Marion, Gérard; Graciaa, Alain; Nesterov, Anatoliy N

    2005-09-15

    A method for modeling the heating curve for gas hydrate dissociation in porous media at isochoric conditions (constant cell volume) is presented. This method consists of using an equation of state of the gas, the cumulative volume distribution (CVD) of the porous medium, and a van der Waals-Platteeuw-type thermodynamic model that includes a capillary term. The proposed method was tested to predict the heating curves for methane hydrate dissociation in a mesoporous silica glass for saturated conditions (liquid volume = pore volume) and for a fractional conversion of water to hydrate of 1 (100% of the available water was converted to hydrate). The shape factor (F) of the hydrate-water interface was found equal to 1, supporting a cylindrical shape for the hydrate particles during hydrate dissociation. Using F = 1, it has been possible to predict the heating curve for different ranges of pressure and temperature. The excellent agreement between the calculated and experimental heating curves supports the validity of our approach. PMID:16853195

  17. Photoinduced ionization and dissociation of aniline-(methanol)n clusters

    NASA Astrophysics Data System (ADS)

    Park, Hye Sun; Nam, Sang Hwan; Song, Jae Kyu; Park, Seung Min

    2007-04-01

    A linear tandem-type time-of-flight mass spectrometer was employed to study unimolecular dissociation of metastable aniline+-(methanol)n (An+-(CH3OH)n, n = 2-9) cluster cations formed by two-photon ionization of neutral clusters. The dominant dissociation channel was to liberate a single methanol molecule, namely, An+-(CH3OH)n --> An+-(CH3OH)n-1 + CH3OH. The decay time constant of the ions ranged from 65 to 460 [mu]s and turned out to be highly dependent on the cluster size. Also, hydrogen transfer mechanism in the formation of An+-(CH3OH)nH was examined by analyzing experimental results from isotopomers, such as deuterated An-d7+-(CH3OD) and An-d7+-(CD3OD) cluster ions. Density functional theory calculations were carried out to obtain optimized structures for neutral and ionic clusters and to support mechanisms related to the hydrogen transfer and unimolecular dissociation reaction.

  18. Piperidine derivatives as nonprostanoid IP receptor agonists.

    PubMed

    Hayashi, Ryoji; Sakagami, Hideki; Koiwa, Masakazu; Ito, Hiroaki; Miyamoto, Mitsuko; Isogaya, Masafumi

    2016-05-01

    The discovery of a new class of nonprostanoid prostaglandin I2 receptor (IP receptor) agonists is reported. Among them, the unique piperidine derivative 31b (2-((1-(2-(N-(4-tolyl)benzamido)ethyl)piperidin-4-yl)oxy)acetic acid) was a good IP receptor agonist and was 50-fold more selective for the human IP receptor than for other human prostanoid receptors. This compound showed good pharmacokinetic properties in dog. PMID:26996371

  19. Dielectric Constant of Suspensions

    NASA Astrophysics Data System (ADS)

    Mendelson, Kenneth S.; Ackmann, James J.

    1997-03-01

    We have used a finite element method to calculate the dielectric constant of a cubic array of spheres. Extensive calculations support preliminary conclusions reported previously (K. Mendelson and J. Ackmann, Bull. Am. Phys. Soc. 41), 657 (1996).. At frequencies below 100 kHz the real part of the dielectric constant (ɛ') shows oscillations as a function of the volume fraction of suspension. These oscillations disappear at low conductivities of the suspending fluid. Measurements of the dielectric constant (J. Ackmann, et al., Ann. Biomed. Eng. 24), 58 (1996). (H. Fricke and H. Curtis, J. Phys. Chem. 41), 729 (1937). are not sufficiently sensitive to show oscillations but appear to be consistent with the theoretical results.

  20. Elastic constants of calcite

    USGS Publications Warehouse

    Peselnick, L.; Robie, R.A.

    1962-01-01

    The recent measurements of the elastic constants of calcite by Reddy and Subrahmanyam (1960) disagree with the values obtained independently by Voigt (1910) and Bhimasenachar (1945). The present authors, using an ultrasonic pulse technique at 3 Mc and 25??C, determined the elastic constants of calcite using the exact equations governing the wave velocities in the single crystal. The results are C11=13.7, C33=8.11, C44=3.50, C12=4.82, C13=5.68, and C14=-2.00, in units of 1011 dyncm2. Independent checks of several of the elastic constants were made employing other directions and polarizations of the wave velocities. With the exception of C13, these values substantially agree with the data of Voigt and Bhimasenachar. ?? 1962 The American Institute of Physics.

  1. Molecular dissociation in dilute gas

    SciTech Connect

    Renfrow, S.N.; Duggan, J.L.; McDaniel, F.D. |

    1999-06-01

    The charge state distributions (CSD) produced during molecular dissociation are important to both Trace Element Accelerator Mass Spectrometry (TEAMS) and the ion implantation industry. The CSD of 1.3{endash}1.7 MeV SiN{sup +}, SiMg{sup +}, SiMn{sup +}, and SiZn{sup +} molecules have been measured for elements that do not form atomic negative ions (N, Mg, Mn, and Zn) using a NEC Tandem Pelletron accelerator. The molecules were produced in a Cs sputter negative ion source, accelerated, magnetically analyzed, and then passed through an N{sub 2} gas cell. The neutral and charged breakups where analyzed using an electrostatic deflector and measured with particle detectors. Equilibrium CSD were determined and comparisons made between molecular and atomic ion data. {copyright} {ital 1999 American Institute of Physics.}

  2. The Dissociative Recombination of OH(+)

    NASA Technical Reports Server (NTRS)

    Guberman, Steven L.

    1995-01-01

    Theoretical quantum chemical calculations of the cross sections and rates for the dissociative recombination of the upsilon = 0 level of the ground state of OH(+) show that recombination occurs primarily along the 2 (2)Pi diabatic route. The products are 0((1)D) and a hot H atom with 6.1 eV kinetic energy. The coupling to the resonances is very small and the indirect recombination mechanism plays only a minor role. The recommended value for the rate coefficient is (6.3 +/- 0.7) x 10(exp -9)x (T(e)/1300)(exp -0.48) cu.cm/s for 10 less than T(e) less than 1000 K.

  3. XrayOpticsConstants

    2005-06-20

    This application (XrayOpticsConstants) is a tool for displaying X-ray and Optical properties for a given material, x-ray photon energy, and in the case of a gas, pressure. The display includes fields such as the photo-electric absorption attenuation length, density, material composition, index of refraction, and emission properties (for scintillator materials).

  4. Dissociative recombination of highly symmetric polyatomic ions.

    PubMed

    Douguet, Nicolas; Orel, Ann E; Greene, Chris H; Kokoouline, Viatcheslav

    2012-01-13

    A general first-principles theory of dissociative recombination is developed for highly symmetric molecular ions and applied to H(3)O(+) and CH(3)(+), which play an important role in astrophysical, combustion, and laboratory plasma environments. The theoretical cross sections obtained for the dissociative recombination of the two ions are in good agreement with existing experimental data from storage ring experiments. PMID:22324682

  5. A Hierarchical Process-Dissociation Model

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Lu, Jun; Morey, Richard D.; Sun, Dongchu; Speckman, Paul L.

    2008-01-01

    In fitting the process-dissociation model (L. L. Jacoby, 1991) to observed data, researchers aggregate outcomes across participant, items, or both. T. Curran and D. L. Hintzman (1995) demonstrated how biases from aggregation may lead to artifactual support for the model. The authors develop a hierarchical process-dissociation model that does not…

  6. Dissociation and the Development of Psychopathology.

    ERIC Educational Resources Information Center

    Putnam, Frank W.; Trickett, Penelope K.

    This paper reviews the research on dissociation and the development of psychopathology in children and adolescents. Definitions and dimensions of dissociation are addressed, noting its range from normative daydreaming to the extremes found in individuals with multiple personality disorder. Memory dysfunctions, disturbances of identity, passive…

  7. Dissociative depression among women in the community.

    PubMed

    Sar, Vedat; Akyüz, Gamze; Oztürk, Erdinç; Alioğlu, Firdevs

    2013-01-01

    This study screened the prevalence and correlates of dissociative disorders among depressive women in the general population. The Dissociative Disorders Interview Schedule and the posttraumatic stress disorder (PTSD) and borderline personality disorder sections of the Structured Clinical Interview for DSM-IV were administered to 628 women in 500 homes. The prevalence of current major depressive episode was 10.0%. Of the women, 26 (40.6%) had the lifetime diagnosis of a DSM-IV, dissociative disorder, yielding a prevalence of 4.1% for dissociative depression. This group was younger (mean age = 30.7 years) than the nondissociative depression women (mean age = 39.6 years). There was no difference between the 2 groups on comorbid somatization disorder, PTSD, or borderline personality disorder. Besides suicide attempts, the dissociative group was characterized by secondary features of dissociative identity disorder; Schneiderian symptoms; borderline personality disorder criteria; and extrasensory perceptions, including possession experiences. They reported suicidality, thoughts of guilt and worthlessness, diminished concentration and indecisiveness, and appetite and weight changes more frequently than the nondissociative group. Early cessation of school education and childhood sexual abuse were frequently reported by the dissociative depression group. With its distinct features, the concept of dissociative depression may facilitate understanding of treatment resistance in, development of better psychotherapy strategies for, and new thinking on the neurobiology and pharmacotherapy of depressive disorders. PMID:23796173

  8. Recent developments in the theory of dissociation

    PubMed Central

    SPITZER, CARSTEN; BARNOW, SVEN; FREYBERGER, HARALD J; GRABE, HANS JOERGEN

    2006-01-01

    Although the construct of dissociation was introduced into psychiatry at the end of the 19th century by Pierre Janet, the term still lacks a coherent conceptualization, which is partially reflected by differences in the classification of dissociative and conversion disorders in ICD-10 and DSM-IV. Given the clinical significance of dissociative psychopathology in numerous clinical conditions, it is very valuable that various efforts have been made to refine and to specify current conceptualizations in recent years. The most promising and convincing approaches converge in subdividing dissociation into qualitatively different types, i.e. pathological versus non-pathological dissociation, and "detachment" versus "compartmentalization". We review these concepts and discuss their scientific and clinical potential as well as their limitations. PMID:16946940

  9. The Shutdown Dissociation Scale (Shut-D)

    PubMed Central

    Schalinski, Inga; Schauer, Maggie; Elbert, Thomas

    2015-01-01

    The evolutionary model of the defense cascade by Schauer and Elbert (2010) provides a theoretical frame for a short interview to assess problems underlying and leading to the dissociative subtype of posttraumatic stress disorder. Based on known characteristics of the defense stages “fright,” “flag,” and “faint,” we designed a structured interview to assess the vulnerability for the respective types of dissociation. Most of the scales that assess dissociative phenomena are designed as self-report questionnaires. Their items are usually selected based on more heuristic considerations rather than a theoretical model and thus include anything from minor dissociative experiences to major pathological dissociation. The shutdown dissociation scale (Shut-D) was applied in several studies in patients with a history of multiple traumatic events and different disorders that have been shown previously to be prone to symptoms of dissociation. The goal of the present investigation was to obtain psychometric characteristics of the Shut-D (including factor structure, internal consistency, retest reliability, predictive, convergent and criterion-related concurrent validity). A total population of 225 patients and 68 healthy controls were accessed. Shut-D appears to have sufficient internal reliability, excellent retest reliability, high convergent validity, and satisfactory predictive validity, while the summed score of the scale reliably separates patients with exposure to trauma (in different diagnostic groups) from healthy controls. The Shut-D is a brief structured interview for assessing the vulnerability to dissociate as a consequence of exposure to traumatic stressors. The scale demonstrates high-quality psychometric properties and may be useful for researchers and clinicians in assessing shutdown dissociation as well as in predicting the risk of dissociative responding. PMID:25976478

  10. A classical trajectory study of the dissociation and isomerization of C2H5.

    PubMed

    Wagner, Albert F; Rivera-Rivera, Luis A; Bachellerie, Damien; Perry, Jamin W; Thompson, Donald L

    2013-11-21

    Motivated by photodissociation experiments in which non-RRKM nanosecond lifetimes of the ethyl radical were reported, we have performed a classical trajectory study of the dissociation and isomerization of C2H5 over the energy range 100-150 kcal/mol. We used a customized version of the AIREBO semiempirical potential (Stuart, S. J.; et al. J. Chem. Phys. 2000, 112, 6472-6486) to more accurately describe the gas-phase decomposition of C2H5. This study constitutes one of the first gas-phase applications of this potential form. At each energy, 10,000 trajectories were run and all underwent dissociation in less than 100 ps. The calculated dissociation rate constants are consistent with RRKM models; no evidence was found for nanosecond lifetimes. An analytic kinetics model of isomerization/dissociation competition was developed that incorporated incomplete mode mixing through a postulated divided phase space. The fits of the model to the trajectory data are good and represent the trajectory results in detail through repeated isomerizations at all energies. The model correctly displays single exponential decay at lower energies, but at higher energies, multiexponential decay due to incomplete mode mixing becomes more apparent. At both ends of the energy range, we carried out similar trajectory studies on CD2CH3 to examine isotopic scrambling. The results largely support the assumption that a H or a D atom is equally likely to dissociate from the mixed-isotope methyl end of the molecule. The calculated fraction of products that have the D atom dissociation is ∼20%, twice the experimental value available at one energy within our range. The calculated degree of isotopic scrambling is non-monotonic with respect to energy due to a non-monotonic ratio of the isomerization to dissociation rate constants. PMID:23448205

  11. Dissociation and Memory Fragmentation in Posttraumatic Stress Disorder: An Evaluation of the Dissociative Encoding Hypothesis

    PubMed Central

    Bedard-Gilligan, Michele; Zoellner, Lori A.

    2012-01-01

    Several prominent theories of posttraumatic stress disorder (PTSD) posit that peritraumatic dissociation results in insufficient encoding of the trauma memory and that persistent dissociation prevents memory elaboration, resulting in memory fragmentation and PTSD. In this review, we summarize the empirical literature on peritraumatic and trait dissociation and trauma narrative fragmentation as measured by meta-memory and rater/objective coding. Across 16 studies to date, the association between dissociation and fragmentation was most prominent when examining peritraumatic dissociation and patient's own ratings of memory fragmentation. This relationship did not hold when examining trait dissociation or rater-coded or computer-generated measures of fragmentation. Thus, initial evidence points more toward a strong self-reported association between constructs that is not supported on more objective fragmentation coding. Measurement overlap, construct ambiguity, and exclusion of potential confounds may underlie lack of a strong association between dissociation and objective-rated fragmentation. PMID:22348400

  12. High fidelity modeling of thermal relaxation and dissociation of oxygen

    NASA Astrophysics Data System (ADS)

    Andrienko, Daniil A.; Boyd, Iain D.

    2015-11-01

    A master equation study of vibrational relaxation and dissociation of oxygen is conducted using state-specific O2-O transition rates, generated by extensive trajectory simulations. Both O2-O and O2-O2 collisions are concurrently simulated in the evolving nonequilibrium gas system under constant heat bath conditions. The forced harmonic oscillator model is incorporated to simulate the state-to-state relaxation of oxygen in O2-O2 collisions. The system of master equations is solved to simulate heating and cooling flows. The present study demonstrates the importance of atom-diatom collisions due to the extremely efficient energy randomization in the intermediate O3 complex. It is shown that the presence of atomic oxygen has a significant impact on vibrational relaxation time at temperatures observed in hypersonic flow. The population of highly-excited O2 vibrational states is affected by the amount of atomic oxygen when modeling the relaxation under constant heat bath conditions. A model of coupled state-to-state vibrational relaxation and dissociation of oxygen is also discussed.

  13. High fidelity modeling of thermal relaxation and dissociation of oxygen

    SciTech Connect

    Andrienko, Daniil A. Boyd, Iain D.

    2015-11-15

    A master equation study of vibrational relaxation and dissociation of oxygen is conducted using state-specific O{sub 2}–O transition rates, generated by extensive trajectory simulations. Both O{sub 2}–O and O{sub 2}–O{sub 2} collisions are concurrently simulated in the evolving nonequilibrium gas system under constant heat bath conditions. The forced harmonic oscillator model is incorporated to simulate the state-to-state relaxation of oxygen in O{sub 2}–O{sub 2} collisions. The system of master equations is solved to simulate heating and cooling flows. The present study demonstrates the importance of atom-diatom collisions due to the extremely efficient energy randomization in the intermediate O{sub 3} complex. It is shown that the presence of atomic oxygen has a significant impact on vibrational relaxation time at temperatures observed in hypersonic flow. The population of highly-excited O{sub 2} vibrational states is affected by the amount of atomic oxygen when modeling the relaxation under constant heat bath conditions. A model of coupled state-to-state vibrational relaxation and dissociation of oxygen is also discussed.

  14. Wall of fundamental constants

    SciTech Connect

    Olive, Keith A.; Peloso, Marco; Uzan, Jean-Philippe

    2011-02-15

    We consider the signatures of a domain wall produced in the spontaneous symmetry breaking involving a dilatonlike scalar field coupled to electromagnetism. Domains on either side of the wall exhibit slight differences in their respective values of the fine-structure constant, {alpha}. If such a wall is present within our Hubble volume, absorption spectra at large redshifts may or may not provide a variation in {alpha} relative to the terrestrial value, depending on our relative position with respect to the wall. This wall could resolve the contradiction between claims of a variation of {alpha} based on Keck/Hires data and of the constancy of {alpha} based on Very Large Telescope data. We derive the properties of the wall and the parameters of the underlying microscopic model required to reproduce the possible spatial variation of {alpha}. We discuss the constraints on the existence of the low-energy domain wall and describe its observational implications concerning the variation of the fundamental constants.

  15. Renormalization of Newton's constant

    NASA Astrophysics Data System (ADS)

    Falls, Kevin

    2015-12-01

    The problem of obtaining a gauge independent beta function for Newton's constant is addressed. By a specific parametrization of metric fluctuations a gauge independent functional integral is constructed for the semiclassical theory around an arbitrary Einstein space. The effective action then has the property that only physical polarizations of the graviton contribute, while all other modes cancel with the functional measure. We are then able to compute a gauge independent beta function for Newton's constant in d dimensions to one-loop order. No Landau pole is present provided Ng<18 , where Ng=d (d -3 )/2 is the number of polarizations of the graviton. While adding a large number of matter fields can change this picture, the absence of a pole persists for the particle content of the standard model in four spacetime dimensions.

  16. Investigations into factors determining the duration of action of the beta 2-adrenoceptor agonist, salmeterol.

    PubMed Central

    Nials, A. T.; Sumner, M. J.; Johnson, M.; Coleman, R. A.

    1993-01-01

    1. This study has explored the mechanism underlying the long duration of action of the beta 2-adrenoceptor agonist, salmeterol. 2. Salmeterol, salbutamol and isoprenaline caused a concentration-related inhibition of electrically-induced contractile responses of the guinea-pig superfused trachea preparation. The effects of both isoprenaline and salbutamol were rapid in onset and rapidly reversed upon removal of the agonist. In contrast, the effects of salmeterol were slower in onset and could not be reversed by superfusion of the tissue with agonist-free Krebs solution even for periods of up to 10 h. 3. The effects of salmeterol were, however, readily reversed by a number of beta-adrenoceptor blocking drugs, as was the effect of a continuous infusion of isoprenaline. Upon removal of the antagonist, however, the effects of salmeterol and of the isoprenaline infusion were reasserted at a rate which was inversely related to the lipophilicity of a beta-adrenoceptor blocking drugs. 4. Salmeterol inhibited the binding of [125I]-(-)-iodopindolol (100 pM) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC50 6.2) and salbutamol (pIC50 5.1) having lower potencies. The inhibition of binding by salmeterol was apparently non-competitive, whereas that produced by salbutamol and isoprenaline was competitive in nature. 5. Isoprenaline and salbutamol rapidly dissociated from their binding sites, whereas in marked contrast, the binding of salmeterol showed no dissociation for periods of up to 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8095419

  17. Varying constants quantum cosmology

    SciTech Connect

    Leszczyńska, Katarzyna; Balcerzak, Adam; Dabrowski, Mariusz P. E-mail: abalcerz@wmf.univ.szczecin.pl

    2015-02-01

    We discuss minisuperspace models within the framework of varying physical constants theories including Λ-term. In particular, we consider the varying speed of light (VSL) theory and varying gravitational constant theory (VG) using the specific ansätze for the variability of constants: c(a) = c{sub 0} a{sup n} and G(a)=G{sub 0} a{sup q}. We find that most of the varying c and G minisuperspace potentials are of the tunneling type which allows to use WKB approximation of quantum mechanics. Using this method we show that the probability of tunneling of the universe ''from nothing'' (a=0) to a Friedmann geometry with the scale factor a{sub t} is large for growing c models and is strongly suppressed for diminishing c models. As for G varying, the probability of tunneling is large for G diminishing, while it is small for G increasing. In general, both varying c and G change the probability of tunneling in comparison to the standard matter content (cosmological term, dust, radiation) universe models.

  18. Connecting Fundamental Constants

    SciTech Connect

    Di Mario, D.

    2008-05-29

    A model for a black hole electron is built from three basic constants only: h, c and G. The result is a description of the electron with its mass and charge. The nature of this black hole seems to fit the properties of the Planck particle and new relationships among basic constants are possible. The time dilation factor in a black hole associated with a variable gravitational field would appear to us as a charge; on the other hand the Planck time is acting as a time gap drastically limiting what we are able to measure and its dimension will appear in some quantities. This is why the Planck time is numerically very close to the gravitational/electric force ratio in an electron: its difference, disregarding a {pi}{radical}(2) factor, is only 0.2%. This is not a coincidence, it is always the same particle and the small difference is between a rotating and a non-rotating particle. The determination of its rotational speed yields accurate numbers for many quantities, including the fine structure constant and the electron magnetic moment.

  19. The Hubble Constant

    NASA Astrophysics Data System (ADS)

    Jackson, Neal

    2015-09-01

    I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give H_0 values of around 72-74 km s^-1 Mpc^-1, with typical errors of 2-3 km s^-1 Mpc^-1. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68 km s^-1 Mpc^-1 and typical errors of 1-2 km s^-1 Mpc^-1. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.

  20. Exciton dissociation at organic small molecule donor-acceptor interfaces (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Robey, Steven W.

    2015-08-01

    Exciton dissociation at organic semiconductor donor-acceptor (D-A) heterojunctions is critical for the performance of organic photovoltaic (OPV) structures. Interfacial charge separation and recombination processes control device efficiency. We have investigated these fundamental interfacial issues using time-resolved two-photon photoemission (TR-2PPE), coupled with the formation of well-controlled D-A structures by organic molecular beam epitaxy. The interfacial electronic and molecular structure of these model interfaces was well-characterized using scanning tunneling microscopy and ultraviolet photoemission. Exciton dissociation dynamics were investigated by using a sub-picosecond pump pulse to create Pc π-->π* transitions, producing a population of singlet (S1) Pc excitons. The subsequent decay dynamics of this population was monitored via photoemission with a time-delayed UV pulse. For CuPcC60 interfaces, S1 exciton population decay in the interfacial CuPc layer was much faster than decay in the bulk due to interfacial charge separation. The rate constant for exciton dissociation was found to be ≍ 7 x 10 12 sec-1 (≍ 140 fs). Excitons that lose energy via intersystem crossing (ISC) to triplet levels dissociate approximately 500 to 1000 times slower. The dependence of exciton dissociation on separation was also studied. Exciton dissociation falls of rapidly with distance from the interface. Dissociation from the 2nd, and subsequent, layers of H2Pc is reduced by at least a factor of 10 from that in the interfacial layer. Finally, investigations of the relative efficiency for interfacial exciton dissociation by alternative acceptors based on perylene cores, (perylene tetracarboxylic dianhydride, or PTCDA) compared to fullerene-based acceptors such as C60 will also be discussed.

  1. Kinetics of calcium dissociation from its high-affinity transport sites on sarcoplasmic reticulum ATPase.

    PubMed

    Orlowski, S; Champeil, P

    1991-01-15

    We investigated the kinetics of calcium dissociation from its high-affinity transport sites on sarcoplasmic reticulum Ca2(+)-ATPase by combining fast filtration with stopped-flow fluorescence measurements. At pH 6 and 20 degrees C, in the absence of potassium and in the presence of 20 mM MgCl2, isotopic exchange of bound calcium exhibited biphasic kinetics, with two phases of equal amplitude, regardless of the initial extent of binding site saturation. The rapidly exchangeable site, whose occupancy by calcium controlled the rate constant of the slow phase, had an apparent affinity for calcium of about 3-6 microM. A similar high affinity was also deduced from measurements of the calcium dependence of the rate constant for ATPase fluorescence changes. This affinity was higher than the overall affinity for calcium deduced from the equilibrium binding measurements (dissociation constant of 15-20 microM); this was consistent with the occurrence of cooperativity (Hill coefficient of 1.6-1.8). The drop in intrinsic fluorescence observed upon chelation of calcium was always slightly faster than the dissociation of calcium itself, although the rates for both this drop in fluorescence and calcium dissociation varied slightly from one preparation to the other. This fluorescence drop was therefore mainly due to dissociation of the bound ions, not to slow transconformation of the ATPase. Dissociation of the two bound calcium ions in a medium containing EGTA exhibited monophasic kinetics in the presence of a calcium ionophore, with a rate constant about half that of the fast phase of isotopic exchange. This particular pattern was observed over a wide range of experimental conditions, including the presence of KCl, dimethyl sulfoxide, 4-nonylphenol, or a nucleotide analogue, at pH 6 or 7, and at various temperatures. The kinetics of calcium dissociation under the above various conditions were not correlated with the ATPase affinity for calcium deduced from equilibrium

  2. From state dissociation to status dissociatus.

    PubMed

    Antelmi, Elena; Ferri, Raffaele; Iranzo, Alex; Arnulf, Isabelle; Dauvilliers, Yves; Bhatia, Kailash P; Liguori, Rocco; Schenck, Carlos H; Plazzi, Giuseppe

    2016-08-01

    The states of being are conventionally defined by the simultaneous occurrence of behavioral, neurophysiological and autonomic descriptors. State dissociation disorders are due to the intrusion of features typical of a different state into an ongoing state. Disorders related to these conditions are classified according to the ongoing main state and comprise: 1) Dissociation from prevailing wakefulness as seen in hypnagogic or hypnopompic hallucinations, automatic behaviors, sleep drunkenness, cataplexy and sleep paralysis 2) Dissociation from rapid eye movement (REM) sleep as seen in REM sleep behavior disorder and lucid dreaming and 3) Dissociation from NREM sleep as seen in the disorders of arousal. The extreme expression of states dissociation is characterized by the asynchronous occurrence of the various components of the different states that prevents the recognition of any state of being. This condition has been named status dissociatus. According to the underlying disorders/diseases and to their severity, among status dissociatus we may recognize disorders in which such an extreme dissociation occurs only at night time or intermittently (i.e., autoimmune encephalopathies, narcolepsy type 1 and IgLON5 parasomnia), and others in which it occurs nearly continuously with complete loss of any conventionally defined state of being, and of the circadian pattern (agrypnia excitata). Here, we render a comprehensive review of all diseases/disorders associated with state dissociation and status dissociatus and propose a critical classification of this complex scenario. PMID:26431902

  3. Theory of dissociative tunneling ionization

    NASA Astrophysics Data System (ADS)

    Svensmark, Jens; Tolstikhin, Oleg I.; Madsen, Lars Bojer

    2016-05-01

    We present a theoretical study of the dissociative tunneling ionization process. Analytic expressions for the nuclear kinetic energy distribution of the ionization rates are derived. A particularly simple expression for the spectrum is found by using the Born-Oppenheimer (BO) approximation in conjunction with the reflection principle. These spectra are compared to exact non-BO ab initio spectra obtained through model calculations with a quantum mechanical treatment of both the electronic and nuclear degrees of freedom. In the regime where the BO approximation is applicable, imaging of the BO nuclear wave function is demonstrated to be possible through reverse use of the reflection principle, when accounting appropriately for the electronic ionization rate. A qualitative difference between the exact and BO wave functions in the asymptotic region of large electronic distances is shown. Additionally, the behavior of the wave function across the turning line is seen to be reminiscent of light refraction. For weak fields, where the BO approximation does not apply, the weak-field asymptotic theory describes the spectrum accurately.

  4. Dissociative Ionization of Pyridine by Electron Impact

    NASA Technical Reports Server (NTRS)

    Dateo, Christopher; Huo, Winifred; Kwak, Dochan (Technical Monitor)

    2002-01-01

    In order to understand the damage of biomolecules by electrons, a process important in radiation damage, we undertake a study of the dissociative ionization (DI) of pyridine (C5H5N) from the low-lying ionization channels. The methodology used is the same as in the benzene study. While no experimental DI data are available, we compare the dissociation products from our calculations with the dissociative photoionization measurements of Tixier et al. using dipole (e, e(+) ion) coincidence spectroscopy. Comparisons with the DI of benzene is also made so as to understand the difference in DI between a heterocyclic and an aromatic molecule.

  5. Dissociation of Natural and Artificial Methane Hydrate

    NASA Astrophysics Data System (ADS)

    Misyura, S. Y.

    2016-02-01

    Present work deals with natural and artificial methane hydrate dissociation. The heating of the powder produced due to the temperature difference between the external air and the powder. The dissociation rate was determined by gravimetric method. The range of the partial self-preservation for the natural hydrate is significantly longer than for the artificial one and moved to higher temperatures. The destruction of the natural sample is slower than the artificial one. The time-averaged dissociation rate for the artificial sample is equal to 1,25 %/s and for the natural hydrate corresponds to 0,59 %/s.

  6. Products of Dissociative Recombination in the Ionosphere

    NASA Technical Reports Server (NTRS)

    Cosby, Philip

    1996-01-01

    SRI International undertook a novel experimental measurement of the product states formed by dissociative ro-combination (DR) of C2(+), NO(+), and N2(+) as a function of both electron energy and reactant ion vibrational level. For these measurements we used a recently developed experimental technique for measuring dissociation product distributions that allows both the branching ratios to be accurately determined and the electronic and ro-vibrational state composition of the reactant ions to be specified. DR is the dominant electron loss mechanism in all regions of the ionosphere. In this process, electron attachment to the molecular ion produces an unstable neutral molecule that rapidly dissociates.

  7. Wavepacket theory of collisional dissociation in molecules

    SciTech Connect

    Kulander, K.

    1980-01-01

    An explicit integration scheme is used to solve the time dependent Schroedinger equation for wavepackets which model collisions in the collinear H + H/sub 2/ system. A realistic LEPS-type potential energy surface is used. Collision energies considered are above the dissociation threshold and probabilities for collision induced dissociation are reported. Also quantum mechanical state-to-state transition probabilities are generated. These results are compared to extensive classical trajectory calculations performed on this same system. The time evolution of the wavepacket densities is studied to understand the dynamics of the collinear collisional dissociation process.

  8. beta2-Agonists at the Olympic Games.

    PubMed

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  9. Introduction of a single isomer beta agonist.

    PubMed

    Rau, J L

    2000-08-01

    The release of levalbuterol offers the first approved single-isomer beta agonist for oral inhalation. Data from in vitro studies support the concept that S albuterol is not inactive and may have properties antagonistic to bronchodilation. There is some variability in the results of clinical studies with the separate isomers of albuterol, which suggests the need for further study. The introduction of levalbuterol into general clinical use in managing asthma and chronic obstructive disease should begin to offer additional information on the effects of a single isomer beta agonist in comparison to previous racemic mixtures. PMID:10963321

  10. Phasic and Sustained Fear are Pharmacologically Dissociable in Rats

    PubMed Central

    Miles, Leigh; Davis, Michael; Walker, David

    2011-01-01

    Previous findings suggest differences in the neuroanatomical substrates of short- (seconds) vs longer-duration (minutes) fear responses. We now report that phasic and sustained fear can also be differentiated pharmacologically, based on their response to several treatments that either are or are not clinically effective anxiolytics. For these experiments, short- or long-duration clicker stimuli were paired with footshock. Acoustic startle amplitude was later measured in the absence of the clicker, or within seconds (phasic fear) or minutes (sustained fear) of its onset. Before testing, rats received a single injection of vehicle, the benzodiazepine chlordiazepoxide, the 5HT1A agonist and dopamine D2 antagonist buspirone, the selective serotonin reuptake inhibitor fluoxetine, or a 3-week treatment with either vehicle or fluoxetine. Chlordiazepoxide blocked sustained, but not phasic startle increases. Acute buspirone, which is not anxiolytic in human beings, did not affect sustained startle increases, but did disrupt phasic increases. Chronic fluoxetine blocked sustained startle increases and unreliably reduced phasic increases; acute fluoxetine affected neither. The results indicate that phasic and sustained fear responses can be pharmacologically dissociated, further validating this distinction, and suggest that sustained startle increases may be especially useful as anxiety models and anxiolytic screens. PMID:21471958

  11. A theoretical analysis of photoactivated unimolecular dissociation: The overtone dissociation of t-butyl hydroperoxide

    NASA Astrophysics Data System (ADS)

    Chandler, David W.; Miller, James A.

    1984-07-01

    We have used the master equation formalism to analyze the photoactivated unimolecular dissociation of a large polyatomic molecule, t-butyl hydroperoxide (t-BuOOH). Our results are compared to the experimental results of Chandler, Farneth, and Zare and of Chuang et al. We find that the curvature in their Stern-Volmer plots cannot be explained by a collisional energy transfer mechanism. At high pressure, the theoretical Stern-Volmer plots are linear, independent of the collisional energy transfer properties. This linearity is related to the existence of a limiting high pressure ``reactive distribution.'' We identify three different pressure regimes that exist in photoactivated unimolecular reaction experiments, and we relate these regimes to the properties of the reactive distribution. In particular, we find that, when a Stern-Volmer analysis is used, curvature at very low pressure can result in systematic errors in determining the unimolecular rate constants. In addition, we have successfully analyzed the real time experiments of Rizzo and Crim using the same molecular model and parameters necessary to predict the experiments of Chandler et al.

  12. Theoretical analysis of photoactivated unimolecular dissociation: The overtone dissociation of t-butyl hydroperoxide

    SciTech Connect

    Chandler, D.W.; Miller, J.A.

    1984-07-01

    We have used the master equation formalism to analyze the photoactivated unimolecular dissociation of a large polyatomic molecule, t-butyl hydroperoxide (t-BuOOH). Our results are compared to the experimental results of Chandler, Farneth, and Zare and of Chuang et al. We find that the curvature in their Stern-Volmer plots cannot be explained by a collisional energy transfer mechanism. At high pressure, the theoretical Stern--Volmer plots are linear, independent of the collisional energy transfer properties. This linearity is related to the existence of a limiting high pressure ''reactive distribution.'' We identify three different pressure regimes that exist in photoactivated unimolecular reaction experiments, and we relate these regimes to the properties of the reactive distribution. In particular, we find that, when a Stern-Volmer analysis is used, curvature at very low pressure can result in systematic errors in determining the unimolecular rate constants. In addition, we have successfully analyzed the real time experiments of Rizzo and Crim using the same molecular model and parameters necessary to predict the experiments of Chandler et al.

  13. Shock wave study of the thermal dissociations of C3F6 and c-C3F6. II. dissociation of hexafluorocyclopropane and dimerization of CF2.

    PubMed

    Cobos, C J; Sölter, L; Tellbach, E; Troe, J

    2014-07-10

    The thermal dissociation of c-C3F6 has been studied in shock waves over the range 620-1030 K monitoring the UV absorption of CF2. The reaction was studied close to its high-pressure limit, but some high-temperature falloff was accounted for. Quantum-chemical and kinetic modeling rationalized the experimental data. The reaction is suggested to involve the 1,3 biradical CF2CF2CF2 intermediate. CF2 formed by the dissociation of c-C3F6 dimerizes to C2F4. The measured rate of this reaction is also found to correspond to the falloff range. Rate constants for 2CF2 → C2F4 as a function of temperature and bath gas concentration [Ar] are given and shown to be consistent with literature values for the high-pressure rate constants from experiments at lower temperatures and dissociation rate constants obtained in the falloff range at higher temperatures. The onset of falloff at intermediate temperatures is analyzed. PMID:24905207

  14. Dissociative identity disorder presenting as dermatitis artefacta.

    PubMed

    Ozmen, Mine; Erdogan, Ayten; Aydemir, Ertugrul H; Oguz, Oya

    2006-06-01

    Dermatitis artefacta is a rare psychiatric condition characterized by rubbing of skin blisters and denial of self-infliction. Dissociation may be comorbid with self-injurious behavior. A background of emotional disturbances during formative years and in later life often results in feelings of isolation and insecurity, which can lead to dissociation as a primary defense mechanism used to overcome traumatic events. In this case report, we describe a female patient with dermatitis artefacta associated with dissociative identity disorder. The patient was a 14-year-old girl. Multiple large, deep ulcerations with unnatural shapes were seen on her left forearm. The ulcerations were thought to be self-inflicted. Psychiatric examination revealed that she had a different identity, and inflicted the lesions when this was assumed. This case leads us to suggest that patients with dermatitis artefacta might have comorbid dissociative experiences, which cannot be identified easily. PMID:16796649

  15. Collision-induced gas phase dissociation rates

    NASA Technical Reports Server (NTRS)

    Hansen, C. Frederick

    1990-01-01

    The Landau-Zener theory of reactive cross sections was applied to diatomic molecules dissociating from a ladder of vibrational states. The result predicts a dissociation rate that is quite well duplicated by an Arrhenius function having a preexponential temperature dependence of about T(sub -1/2), at least for inert collision partners. This relation fits experimental data reasonably well. The theory is then used to calculate the effect of vibrational nonequilibrium on dissociation rate. For Morse oscillators, the results are about the same as given by Hammerling, Kivel, and Teare in their analytic approximation for harmonic oscillators, though at very high temperature a correction for the partition function limit is included. The empirical correction for vibration nonequilibrium proposed by Park, which is a convenient algorithm for CFD calculations, is modified to prevent a drastic underestimation of dissociation rates that occurs with this method when vibrational temperature is much smaller than the kinetic temperature of the gas.

  16. Research Reports: Hallucinogens and Dissociative Drugs

    MedlinePlus

    ... in bizarre or dangerous behavior. Hallucinogens such as LSD, psilocybin, peyote, DMT, and ayahuasca cause emotions to ... Take Hallucinogenic or Dissociative Drugs? How Do Hallucinogens (LSD, Psilocybin, Peyote, DMT, and Ayahuasca) Affect the Brain ...

  17. A comparison of the equilibrium constants for the dissociation of carbonic acid in seawater media

    NASA Astrophysics Data System (ADS)

    Dickson, A. G.; Millero, F. J.

    1987-10-01

    The published experimental data of Hansson and of Mehrbach et al. have been critically compared after adjustment to a common pH scale based upon total hydrogen ion concentration. No significant systematic differences are found within the overall experimental error of the data. The results have been pooled to yield reliable equations that can be used to estimate pK 1∗and pK 2∗ for seawater media a salinities from 0 to 40 and at temperatures from 2 to 35°C.

  18. Determination of the inhibitor dissociation constant of an individual unmodified enzyme molecule in free solution.

    PubMed

    Crawford, Jeremie J; Hollett, Joshua W; Craig, Douglas B

    2016-08-01

    Single enzyme molecule assays on E. coli β-galactosidase were performed using a capillary electrophoresis-based method. Three types of assays were performed. The catalytic rate of 20 individual molecules was assayed in duplicate in the presence of 50 μM substrate. The ratio of rates for the second incubation relative to the first was 0.96 ± 0.03, showing the reproducibility of the method. In the second assay, the rates were determined in the absence and presence of 210 μM L-ribose, a competitive inhibitor. The ratio of the rate in the presence of inhibitor to that in its absence for 19 individual molecules was 0.44 ± 0.23. This large relative standard deviation suggests that each individual enzyme molecule was affected to a different extent by the presence of the inhibitor, which is consistent with KI being heterogeneous. To estimate KI for individual molecules, a third assay was performed. Each molecule was incubated in the presence of 30 and 50 μM substrate and then in the presence of 50 μM substrate plus 210 μM inhibitor. Comparison of the rates in the two substrate concentrations allowed for the determination of the individual Km of each molecule. From this value and the difference in rates in the presence and absence of inhibitor, the individual molecule KI values were determined. This value was found to differ between individual molecules and was found to increase with an increase in Km . Modeling showed that a heterogeneity in KI results in an alteration in the Michaelis-Menten curve for a population of enzymes in the presence of a competitive inhibitor. PMID:27271375

  19. Dissociation energy of molecules in dense gases

    NASA Technical Reports Server (NTRS)

    Kunc, J. A.

    1992-01-01

    A general approach is presented for calculating the reduction of the dissociation energy of diatomic molecules immersed in a dense (n = less than 10 exp 22/cu cm) gas of molecules and atoms. The dissociation energy of a molecule in a dense gas differs from that of the molecule in vacuum because the intermolecular forces change the intramolecular dynamics of the molecule, and, consequently, the energy of the molecular bond.

  20. Dissociative Ionization of Benzene by Electron Impact

    NASA Technical Reports Server (NTRS)

    Huo, Winifred; Dateo, Christopher; Kwak, Dochan (Technical Monitor)

    2002-01-01

    We report a theoretical study of the dissociative ionization (DI) of benzene from the low-lying ionization channels. Our approach makes use of the fact that electron motion is much faster than nuclear motion and DI is treated as a two-step process. The first step is electron-impact ionization resulting in an ion with the same nuclear geometry as the neutral molecule. In the second step the nuclei relax from the initial geometry and undergo unimolecular dissociation. For the ionization process we use the improved binary-encounter dipole (iBED) model. For the unimolecular dissociation step, we study the steepest descent reaction path to the minimum of the ion potential energy surface. The path is used to analyze the probability of unimolecular dissociation and to determine the product distributions. Our analysis of the dissociation products and the thresholds of the productions are compared with the result dissociative photoionization measurements of Feng et al. The partial oscillator strengths from Feng et al. are then used in the iBED cross section calculations.

  1. Collision induced dissociation of alpha hydroxy acids

    NASA Astrophysics Data System (ADS)

    Bandu, Mary L.; Grubbs, Thomas; Kater, Marcus; Desaire, Heather

    2006-03-01

    Alpha hydroxy acids typically dissociate in tandem mass spectrometric experiments to produce product ions representing a neutral loss of 46 Da (CH2O2) in negative ion mode. Although it is widely accepted that the carboxylate group is lost in the dissociation process, the origin of the remaining two hydrogens is unclear. The current study utilizes an alpha hydroxy acid chemical library and deuterium labeling experiments to identify the origin of the two hydrogens lost during dissociation. Secondly, this study investigates the lower m/z region of the CID spectrum, a region previously unexplored, to aid in characterizing the dissociation mechanism. Further experiments testing the energy requirements and time parameters of the dissociation also are consistent with criteria previously defined for ion-neutral complex formation. In addition to describing the mechanism for the loss of CH2O2, we have conducted experiments that demonstrate the important chemical features of molecules that can prevent alpha hydroxy acids from undergoing the loss of 46 Da. By understanding the chemical composition of the 46 Da loss, the dissociation mechanism responsible for the loss, and the factors that hinder this mechanistic pathway, chemical information about alpha hydroxy acids can be obtained from their CID data.

  2. Unimolecular dissociation of cyclopentadiene and indene

    SciTech Connect

    Yi, W.; Chattopadhyay, A.; Bersohn, R. )

    1991-05-01

    The dissociation of hydrogen atoms from the methylene group of cyclopentadiene (CP) and indene (ID) excited with a 193 nm photon has been studied by hydrogen atom laser induced fluorescence. The rate of dissociation of IND was 7.4{times}10{sup 6} s{sup {minus}1} but that of CP was too fast to measure. The ratio of H atoms to D atoms generated from 5-deuteriocyclopentadiene (5-dCP) was 3.91{plus minus}0.46. Rice--Ramsberger--Kassel--Marcus theory was used to calculate the rates of dissociation of CP and 5-dCP. The quantum yield for dissociating H atoms from CP was 0.85{plus minus}0.07. The ejected H atoms have a Maxwell velocity distribution with temperatures which are equal to the vibrational temperatures, 3690 and 2479 K for CP and IND, respectively. The most important result of the work is this confirmation of an earlier finding on a different set of molecules that the translational temperature of the fragments {ital after} the dissociation is equal to the vibrational temperature {ital before} the dissociation. This is explained by the assumption that the motion of the fast, light hydrogen atom is partly decoupled from that of the heavier, slower atoms.

  3. The Hubble constant.

    PubMed

    Tully, R B

    1993-06-01

    Five methods of estimating distances have demonstrated internal reproducibility at the level of 5-20% rms accuracy. The best of these are the cepheid (and RR Lyrae), planetary nebulae, and surface-brightness fluctuation techniques. Luminosity-line width and Dn-sigma methods are less accurate for an individual case but can be applied to large numbers of galaxies. The agreement is excellent between these five procedures. It is determined that Hubble constant H0 = 90 +/- 10 km.s-1.Mpc-1 [1 parsec (pc) = 3.09 x 10(16) m]. It is difficult to reconcile this value with the preferred world model even in the low-density case. The standard model with Omega = 1 may be excluded unless there is something totally misunderstood about the foundation of the distance scale or the ages of stars. PMID:11607391

  4. When constants are important

    SciTech Connect

    Beiu, V.

    1997-04-01

    In this paper the authors discuss several complexity aspects pertaining to neural networks, commonly known as the curse of dimensionality. The focus will be on: (1) size complexity and depth-size tradeoffs; (2) complexity of learning; and (3) precision and limited interconnectivity. Results have been obtained for each of these problems when dealt with separately, but few things are known as to the links among them. They start by presenting known results and try to establish connections between them. These show that they are facing very difficult problems--exponential growth in either space (i.e. precision and size) and/or time (i.e., learning and depth)--when resorting to neural networks for solving general problems. The paper will present a solution for lowering some constants, by playing on the depth-size tradeoff.

  5. Unitaxial constant velocity microactuator

    DOEpatents

    McIntyre, Timothy J.

    1994-01-01

    A uniaxial drive system or microactuator capable of operating in an ultra-high vacuum environment. The mechanism includes a flexible coupling having a bore therethrough, and two clamp/pusher assemblies mounted in axial ends of the coupling. The clamp/pusher assemblies are energized by voltage-operated piezoelectrics therewithin to operatively engage the shaft and coupling causing the shaft to move along its rotational axis through the bore. The microactuator is capable of repeatably positioning to sub-manometer accuracy while affording a scan range in excess of 5 centimeters. Moreover, the microactuator generates smooth, constant velocity motion profiles while producing a drive thrust of greater than 10 pounds. The system is remotely controlled and piezoelectrically driven, hence minimal thermal loading, vibrational excitation, or outgassing is introduced to the operating environment.

  6. A Constant Pressure Bomb

    NASA Technical Reports Server (NTRS)

    Stevens, F W

    1924-01-01

    This report describes a new optical method of unusual simplicity and of good accuracy suitable to study the kinetics of gaseous reactions. The device is the complement of the spherical bomb of constant volume, and extends the applicability of the relationship, pv=rt for gaseous equilibrium conditions, to the use of both factors p and v. The method substitutes for the mechanical complications of a manometer placed at some distance from the seat of reaction the possibility of allowing the radiant effects of reaction to record themselves directly upon a sensitive film. It is possible the device may be of use in the study of the photoelectric effects of radiation. The method makes possible a greater precision in the measurement of normal flame velocities than was previously possible. An approximate analysis shows that the increase of pressure and density ahead of the flame is negligible until the velocity of the flame approaches that of sound.

  7. The Hubble constant.

    PubMed Central

    Tully, R B

    1993-01-01

    Five methods of estimating distances have demonstrated internal reproducibility at the level of 5-20% rms accuracy. The best of these are the cepheid (and RR Lyrae), planetary nebulae, and surface-brightness fluctuation techniques. Luminosity-line width and Dn-sigma methods are less accurate for an individual case but can be applied to large numbers of galaxies. The agreement is excellent between these five procedures. It is determined that Hubble constant H0 = 90 +/- 10 km.s-1.Mpc-1 [1 parsec (pc) = 3.09 x 10(16) m]. It is difficult to reconcile this value with the preferred world model even in the low-density case. The standard model with Omega = 1 may be excluded unless there is something totally misunderstood about the foundation of the distance scale or the ages of stars. PMID:11607391

  8. Reciprocity of agonistic support in ravens

    PubMed Central

    Fraser, Orlaith N.; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim’s likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  9. Multiple tyrosine metabolites are GPR35 agonists

    PubMed Central

    Deng, Huayun; Hu, Haibei; Fang, Ye

    2012-01-01

    Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown. Here we report the agonist activity of multiple tyrosine metabolites at the GPR35. Tyrosine metabolism intermediates that contain carboxylic acid and/or catechol functional groups were first selected. Whole cell dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor were then used to characterize their agonist activity in native HT-29. Molecular assays including β-arrestin translocation, ERK phosphorylation and receptor internalization confirmed that GPR35 functions as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3′,5′-triiodothyronine, 3,3′,5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine. These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism. PMID:22523636

  10. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  11. Reciprocity of agonistic support in ravens.

    PubMed

    Fraser, Orlaith N; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID:22298910

  12. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    PubMed Central

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  13. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    PubMed

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  14. An improved potential energy surface and multi-temperature quasiclassical trajectory calculations of N2 + N2 dissociation reactions.

    PubMed

    Bender, Jason D; Valentini, Paolo; Nompelis, Ioannis; Paukku, Yuliya; Varga, Zoltan; Truhlar, Donald G; Schwartzentruber, Thomas; Candler, Graham V

    2015-08-01

    Accurate modeling of high-temperature hypersonic flows in the atmosphere requires consideration of collision-induced dissociation of molecular species and energy transfer between the translational and internal modes of the gas molecules. Here, we describe a study of the N2 + N2⟶N2 + 2N and N2 + N2⟶4N nitrogen dissociation reactions using the quasiclassical trajectory (QCT) method. The simulations used a new potential energy surface for the N4 system; the surface is an improved version of one that was presented previously. In the QCT calculations, initial conditions were determined based on a two-temperature model that approximately separates the translational-rotational temperature from the vibrational temperature of the N2 diatoms. Five values from 8000 K to 30,000 K were considered for each of the two temperatures. Over 2.4 × 10(9) trajectories were calculated. We present results for ensemble-averaged dissociation rate constants as functions of the translational-rotational temperature T and the vibrational temperature T(v). The rate constant depends more strongly on T when T(v) is low, and it depends more strongly on T(v) when T is low. Quasibound reactant states contribute significantly to the rate constants, as do exchange processes at higher temperatures. We discuss two sets of runs in detail: an equilibrium test set in which T = T(v) and a nonequilibrium test set in which T(v) < T. In the equilibrium test set, high-v and moderately-low-j molecules contribute most significantly to the overall dissociation rate, and this state specificity becomes stronger as the temperature decreases. Dissociating trajectories tend to result in a major loss of vibrational energy and a minor loss of rotational energy. In the nonequilibrium test set, as T(v) decreases while T is fixed, higher-j molecules contribute more significantly to the dissociation rate, dissociating trajectories tend to result in a greater rotational energy loss, and the dissociation probability

  15. An improved potential energy surface and multi-temperature quasiclassical trajectory calculations of N2 + N2 dissociation reactions

    NASA Astrophysics Data System (ADS)

    Bender, Jason D.; Valentini, Paolo; Nompelis, Ioannis; Paukku, Yuliya; Varga, Zoltan; Truhlar, Donald G.; Schwartzentruber, Thomas; Candler, Graham V.

    2015-08-01

    Accurate modeling of high-temperature hypersonic flows in the atmosphere requires consideration of collision-induced dissociation of molecular species and energy transfer between the translational and internal modes of the gas molecules. Here, we describe a study of the N2 + N2⟶N2 + 2N and N2 + N2⟶4N nitrogen dissociation reactions using the quasiclassical trajectory (QCT) method. The simulations used a new potential energy surface for the N4 system; the surface is an improved version of one that was presented previously. In the QCT calculations, initial conditions were determined based on a two-temperature model that approximately separates the translational-rotational temperature from the vibrational temperature of the N2 diatoms. Five values from 8000 K to 30 000 K were considered for each of the two temperatures. Over 2.4 × 109 trajectories were calculated. We present results for ensemble-averaged dissociation rate constants as functions of the translational-rotational temperature T and the vibrational temperature Tv. The rate constant depends more strongly on T when Tv is low, and it depends more strongly on Tv when T is low. Quasibound reactant states contribute significantly to the rate constants, as do exchange processes at higher temperatures. We discuss two sets of runs in detail: an equilibrium test set in which T = Tv and a nonequilibrium test set in which Tv < T. In the equilibrium test set, high-v and moderately-low-j molecules contribute most significantly to the overall dissociation rate, and this state specificity becomes stronger as the temperature decreases. Dissociating trajectories tend to result in a major loss of vibrational energy and a minor loss of rotational energy. In the nonequilibrium test set, as Tv decreases while T is fixed, higher-j molecules contribute more significantly to the dissociation rate, dissociating trajectories tend to result in a greater rotational energy loss, and the dissociation probability's dependence on v

  16. Thermal dissociation behavior and dissociation enthalpies of methane-carbon dioxide mixed hydrates.

    PubMed

    Kwon, Tae-Hyuk; Kneafsey, Timothy J; Rees, Emily V L

    2011-06-30

    Replacement of methane with carbon dioxide in hydrate has been proposed as a strategy for geologic sequestration of carbon dioxide (CO(2)) and/or production of methane (CH(4)) from natural hydrate deposits. This replacement strategy requires a better understanding of the thermodynamic characteristics of binary mixtures of CH(4) and CO(2) hydrate (CH(4)-CO(2) mixed hydrates), as well as thermophysical property changes during gas exchange. This study explores the thermal dissociation behavior and dissociation enthalpies of CH(4)-CO(2) mixed hydrates. We prepared CH(4)-CO(2) mixed hydrate samples from two different, well-defined gas mixtures. During thermal dissociation of a CH(4)-CO(2) mixed hydrate sample, gas samples from the head space were periodically collected and analyzed using gas chromatography. The changes in CH(4)-CO(2) compositions in both the vapor phase and hydrate phase during dissociation were estimated based on the gas chromatography measurements. It was found that the CO(2) concentration in the vapor phase became richer during dissociation because the initial hydrate composition contained relatively more CO(2) than the vapor phase. The composition change in the vapor phase during hydrate dissociation affected the dissociation pressure and temperature; the richer CO(2) in the vapor phase led to a lower dissociation pressure. Furthermore, the increase in CO(2) concentration in the vapor phase enriched the hydrate in CO(2). The dissociation enthalpy of the CH(4)-CO(2) mixed hydrate was computed by fitting the Clausius-Clapeyron equation to the pressure-temperature (PT) trace of a dissociation test. It was observed that the dissociation enthalpy of the CH(4)-CO(2) mixed hydrate lays between the limiting values of pure CH(4) hydrate and CO(2) hydrate, increasing with the CO(2) fraction in the hydrate phase. PMID:21604671

  17. Modeling electrostatic and heterogeneity effects on proton dissociation from humic substances

    USGS Publications Warehouse

    Tipping, E.; Reddy, M.M.; Hurley, M.A.

    1990-01-01

    The apparent acid dissociation constant of humic substances increases by 2-4 pK units as ionization of the humic carboxylate groups proceeds. This change in apparent acid strength is due in part to the increase in electrical charge on the humic molecules as protons are shed. In addition, proton dissociation reactions are complicated because humic substances are heterogeneous with respect to proton dissociating groups and molecular size. In this paper, we use the Debye-Hu??ckel theory to describe the effects of electrostatic interactions on proton dissociation of humic substances. Simulations show that, for a size-heterogeneous system of molecules, the weight-average molecular weight is preferable to the number-average value for averaging the effects of electrostatic interactions. Analysis of published data on the proton dissociation of fulvic acid from the Suwannee River shows that the electrostatic interactions can be satisfactorily described by a hypothetical homogeneous compound having a molecular weight of 1000 (similar to the experimentally determined weight-average value). Titration data at three ionic strengths, for several fulvic acid concentrations, and in the pH range from 2.9 to 6.4 can be fitted with three adjustable parameters (pK??int values), given information on molecular size and carboxylate group content. ?? 1990 American Chemical Society.

  18. Direct molecular simulation of nitrogen dissociation based on an ab initio potential energy surface

    SciTech Connect

    Valentini, Paolo Schwartzentruber, Thomas E. Bender, Jason D. Nompelis, Ioannis Candler, Graham V.

    2015-08-15

    The direct molecular simulation (DMS) approach is used to predict the internal energy relaxation and dissociation dynamics of high-temperature nitrogen. An ab initio potential energy surface (PES) is used to calculate the dynamics of two interacting nitrogen molecules by providing forces between the four atoms. In the near-equilibrium limit, it is shown that DMS reproduces the results obtained from well-established quasiclassical trajectory (QCT) analysis, verifying the validity of the approach. DMS is used to predict the vibrational relaxation time constant for N{sub 2}–N{sub 2} collisions and its temperature dependence, which are in close agreement with existing experiments and theory. Using both QCT and DMS with the same PES, we find that dissociation significantly depletes the upper vibrational energy levels. As a result, across a wide temperature range, the dissociation rate is found to be approximately 4–5 times lower compared to the rates computed using QCT with Boltzmann energy distributions. DMS calculations predict a quasi-steady-state distribution of rotational and vibrational energies in which the rate of depletion of high-energy states due to dissociation is balanced by their rate of repopulation due to collisional processes. The DMS approach simulates the evolution of internal energy distributions and their coupling to dissociation without the need to precompute rates or cross sections for all possible energy transitions. These benchmark results could be used to develop new computational fluid dynamics models for high-enthalpy flow applications.

  19. Balanced anesthesia and constant-rate infusions in horses.

    PubMed

    Valverde, Alexander

    2013-04-01

    Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions. This review summarizes the different drug combinations used in horses, and provides calculated recommended doses based on the pharmacokinetics of individual drugs. PMID:23498047

  20. Dissociations between developmental dyslexias and attention deficits

    PubMed Central

    Lukov, Limor; Friedmann, Naama; Shalev, Lilach; Khentov-Kraus, Lilach; Shalev, Nir; Lorber, Rakefet; Guggenheim, Revital

    2014-01-01

    We examine whether attention deficits underlie developmental dyslexia, or certain types of dyslexia, by presenting double dissociations between the two. We took into account the existence of distinct types of dyslexia and of attention deficits, and focused on dyslexias that may be thought to have an attentional basis: letter position dyslexia (LPD), in which letters migrate within words, attentional dyslexia (AD), in which letters migrate between words, neglect dyslexia, in which letters on one side of the word are omitted or substituted, and surface dyslexia, in which words are read via the sublexical route. We tested 110 children and adults with developmental dyslexia and/or attention deficits, using extensive batteries of reading and attention. For each participant, the existence of dyslexia and the dyslexia type were tested using reading tests that included stimuli sensitive to the various dyslexia types. Attention deficit and its type was established through attention tasks assessing sustained, selective, orienting, and executive attention functioning. Using this procedure, we identified 55 participants who showed a double dissociation between reading and attention: 28 had dyslexia with normal attention and 27 had attention deficits with normal reading. Importantly, each dyslexia with suspected attentional basis dissociated from attention: we found 21 individuals with LPD, 13 AD, 2 neglect dyslexia, and 12 surface dyslexia without attention deficits. Other dyslexia types (vowel dyslexia, phonological dyslexia, visual dyslexia) also dissociated from attention deficits. Examination of 55 additional individuals with both a specific dyslexia and a certain attention deficit found no attention function that was consistently linked with any dyslexia type. Specifically, LPD and AD dissociated from selective attention, neglect dyslexia dissociated from orienting, and surface dyslexia dissociated from sustained and executive attention. These results indicate that

  1. Molecular dynamics studies of the dissociated screw dislocation in silicon.

    PubMed

    Choudhury, R; Gattinoni, C; Makov, G; De Vita, A

    2010-02-24

    Characterizing the motion of dislocations through covalent, high Peierls barrier materials is a key problem in materials science, while despite the progress in experimental studies the actual observation of the atomistic behaviour involved in core migration remains limited. We have applied a hybrid embedding scheme to investigate the dissociated screw dislocation in silicon, consisting of two 30° partials separated by a stacking fault ribbon, under the influence of a constant external strain. Our 'learn on the fly' hybrid technique allows us to calculate the forces on atoms in the vicinity of the core region using the tight binding Kwon potential, whilst the remainder of the bulk matrix is treated within a classical approximation. Applying a 5% strain to the dissociated screw dislocation, for a simulation time of 100 ps at a temperature of 600 K, we observe movement of the partials through two different mechanisms: double kink formation and square ring diffusion at the core. Our results suggest that in these conditions, the role of solitons or anti-phase defects in seeding kink formation and subsequent migration is an important one, which should be taken into account in future studies. PMID:21386388

  2. Rovibrational energy transfer and dissociation in O2-O collisions

    NASA Astrophysics Data System (ADS)

    Andrienko, Daniil A.; Boyd, Iain D.

    2016-03-01

    A set of state-specific transition rates for each rovibrational level is generated for the O 2 ( X 3 Σg - ) - O (" separators=" 3 P ) system using the quasi-classical trajectory method at temperatures observed in hypersonic flows. A system of master equations describes the relaxation of the rovibrational ensemble to thermal equilibrium under ideal heat bath conditions at a constant translational temperature. Vibrational and rotational relaxation times, obtained from the average internal energies, exhibit a pattern inherent in a chemically reactive collisional pair. An intrinsic feature of the O3 molecular system with a large attractive potential is a weak temperature dependence of the rovibrational transition rates. For this reason, the quasi-steady vibrational and rotational temperatures experience a maximum at increasing translational temperature. The energy rate coefficients, that characterize the average loss of internal energy due to dissociation, quickly diminish at high temperatures, compared to other molecular systems.

  3. Dissociation energies of some high temperature molecules containing aluminum

    NASA Technical Reports Server (NTRS)

    Stearns, C. A.; Kohl, F. J.

    1972-01-01

    The Knudsen cell mass spectrometric method has been used to investigate the gaseous molecules Al2, AlSi,AlSiO, AlC2, Al2C2, and AlAuC2. Special attention was given to the experimental considerations and techniques needed to identify and to measure ion intensities for very low abundance molecular species. Second- and third-law procedures were used to obtain reaction enthalpies for pressure calibration independent and isomolecular exchange reactions. Dissociation energies for the molecules were derived from the measured ion intensities, free-energy functions obtained from estimated molecular constants, and auxiliary thermodynamic data. The bonding and stability of these aluminum containing molecules are compared with other similar species.

  4. Rovibrational energy transfer and dissociation in O2-O collisions.

    PubMed

    Andrienko, Daniil A; Boyd, Iain D

    2016-03-14

    A set of state-specific transition rates for each rovibrational level is generated for the O2(X(3)Σ(g)(-))-O(3)P system using the quasi-classical trajectory method at temperatures observed in hypersonic flows. A system of master equations describes the relaxation of the rovibrational ensemble to thermal equilibrium under ideal heat bath conditions at a constant translational temperature. Vibrational and rotational relaxation times, obtained from the average internal energies, exhibit a pattern inherent in a chemically reactive collisional pair. An intrinsic feature of the O3 molecular system with a large attractive potential is a weak temperature dependence of the rovibrational transition rates. For this reason, the quasi-steady vibrational and rotational temperatures experience a maximum at increasing translational temperature. The energy rate coefficients, that characterize the average loss of internal energy due to dissociation, quickly diminish at high temperatures, compared to other molecular systems. PMID:26979687

  5. Dissociative electron attachment to C{sub 2}F{sub 5} radicals

    SciTech Connect

    Haughey, Sean A.; Field, Thomas A.; Langer, Judith; Shuman, Nicholas S.; Miller, Thomas M.; Friedman, Jeffrey F.; Viggiano, A. A.

    2012-08-07

    Dissociative electron attachment to the reactive C{sub 2}F{sub 5} molecular radical has been investigated with two complimentary experimental methods; a single collision beam experiment and a new flowing afterglow Langmuir probe technique. The beam results show that F{sup -} is formed close to zero electron energy in dissociative electron attachment to C{sub 2}F{sub 5}. The afterglow measurements also show that F{sup -} is formed in collisions between electrons and C{sub 2}F{sub 5} molecules with rate constants of 3.7 Multiplication-Sign 10{sup -9} cm{sup 3} s{sup -1} to 4.7 Multiplication-Sign 10{sup -9} cm{sup 3} s{sup -1} at temperatures of 300-600 K. The rate constant increases slowly with increasing temperature, but the rise observed is smaller than the experimental uncertainty of 35%.

  6. Refractive index change in dissociating shocked benzene

    SciTech Connect

    Erskine, D.J.

    1994-06-01

    A calculation is made of the refractive index of a shocked solution of hydrocarbon species and spheroidal carbon particles that would be the dissociation products of benzene. The results is evaluated for benzene shocked to 15 GPa, both for an arbitrary endpoint distribution of products and reactant, and for a specific endpoint distribution suggested by a statistical-mechanical calculation. In the case of diamond particles, the refractive index is predicted to decrease by a small amount (from 1.96 to 1.75) as the dissociation proceeds. In the case of graphite particles of large oblateness, the refractive index could increase significantly through the dissociation (from 1.96 to 2.75 for infinitely oblate platelets). Thus the measurement of the time dependent refractive index through the dissociation of shocked benzene can indicate the morphology of the carbon particulates as well as the time scale for this reaction. We propose using the refractive index as a measure of completion of the dissociation reaction. This would allow a determination of the instantaneous amount of carbon in particulate form, information which is valuable in conjunction with Mie scattering experiments for example.

  7. Intrinsic disorder accelerates dissociation rather than association.

    PubMed

    Umezawa, Koji; Ohnuki, Jun; Higo, Junichi; Takano, Mitsunori

    2016-08-01

    The intrinsically disordered protein (IDP) has distinct properties both physically and biologically: it often becomes folded when binding to the target and is frequently involved in signal transduction. The physical property seems to be compatible with the biological property where fast association and dissociation between IDP and the target are required. While fast association has been well studied, fueled by the fly-casting mechanism, the dissociation kinetics has received less attention. We here study how the intrinsic disorder affects the dissociation kinetics, as well as the association kinetics, paying attention to the interaction strength at the binding site (i.e., the quality of the "fly lure"). Coarse-grained molecular dynamics simulation of the pKID-KIX system, a well-studied IDP system, shows that the association rate becomes larger as the disorder-inducing flexibility that was imparted to the model is increased, but the acceleration is marginal and turns into deceleration as the quality of the fly lure is worsened. In contrast, the dissociation rate is greatly enhanced as the disorder is increased, indicating that intrinsic disorder serves for rapid signal switching more effectively through dissociation than association. Proteins 2016; 84:1124-1133. © 2016 Wiley Periodicals, Inc. PMID:27122223

  8. Ion-induced dissociation dynamics of acetylene

    SciTech Connect

    De, Sankar; Rajput, Jyoti; Roy, A.; Safvan, C. P.; Ghosh, P. N.

    2008-02-15

    We report on the results of dissociation dynamics of multiple charged acetylene molecules formed in collision with 1.2 MeV Ar{sup 8+} projectiles. Using the coincidence map, we can separate out the different dissociation pathways between carbon and hydrogen ionic fragments as well as complete two-body breakup events. From the measured slopes of the coincidence islands for carbon atomic fragments and theoretical values determined from the charge and momentum distribution of the correlated particles, we observe a diatom like behavior of the C-C charged complex during dissociation of multiply charged C{sub 2}H{sub 2}. We conclude that this behavior in breakup dynamics is a signature of sequentiality in dissociation of this multiply charged molecular species. The shape and orientation of the islands give further information about the momentum balance in the fragmentation process of two- or many-body dissociation pathways. Kinetic energy release of different breakup channels are reported here and compared with values calculated from the pure Coulomb explosion model.

  9. Isotope separation by photoselective dissociative electron capture

    DOEpatents

    Stevens, Charles G. [Pleasanton, CA

    1978-08-29

    A method of separating isotopes based on photoselective electron capture dissociation of molecules having an electron capture cross section dependence on the vibrational state of the molecule. A molecular isotope source material is irradiated to selectively excite those molecules containing a desired isotope to a predetermined vibrational state having associated therewith an electron capture energy region substantially non-overlapping with the electron capture energy ranges associated with the lowest vibration states of the molecules. The isotope source is also subjected to electrons having an energy corresponding to the non-overlapping electron capture region whereby the selectively excited molecules preferentially capture electrons and dissociate into negative ions and neutrals. The desired isotope may be in the negative ion product or in the neutral product depending upon the mechanism of dissociation of the particular isotope source used. The dissociation product enriched in the desired isotope is then separated from the reaction system by conventional means. Specifically, .sup.235 UF.sub.6 is separated from a UF.sub.6 mixture by selective excitation followed by dissociative electron capture into .sup.235 UF.sub.5 - and F.

  10. Isotope separation by photoselective dissociative electron capture

    DOEpatents

    Stevens, C.G.

    1978-08-29

    Disclosed is a method of separating isotopes based on photoselective electron capture dissociation of molecules having an electron capture cross section dependence on the vibrational state of the molecule. A molecular isotope source material is irradiated to selectively excite those molecules containing a desired isotope to a predetermined vibrational state having associated therewith an electron capture energy region substantially non-overlapping with the electron capture energy ranges associated with the lowest vibration states of the molecules. The isotope source is also subjected to electrons having an energy corresponding to the non-overlapping electron capture region whereby the selectively excited molecules preferentially capture electrons and dissociate into negative ions and neutrals. The desired isotope may be in the negative ion product or in the neutral product depending upon the mechanism of dissociation of the particular isotope source used. The dissociation product enriched in the desired isotope is then separated from the reaction system by conventional means. Specifically, [sup 235]UF[sub 6] is separated from a UF[sub 6] mixture by selective excitation followed by dissociative electron capture into [sup 235]UF[sub 5]- and F. 2 figs.

  11. Beyond the Hubble Constant

    NASA Astrophysics Data System (ADS)

    1995-08-01

    about the distances to galaxies and thereby about the expansion rate of the Universe. A simple way to determine the distance to a remote galaxy is by measuring its redshift, calculate its velocity from the redshift and divide this by the Hubble constant, H0. For instance, the measured redshift of the parent galaxy of SN 1995K (0.478) yields a velocity of 116,000 km/sec, somewhat more than one-third of the speed of light (300,000 km/sec). From the universal expansion rate, described by the Hubble constant (H0 = 20 km/sec per million lightyears as found by some studies), this velocity would indicate a distance to the supernova and its parent galaxy of about 5,800 million lightyears. The explosion of the supernova would thus have taken place 5,800 million years ago, i.e. about 1,000 million years before the solar system was formed. However, such a simple calculation works only for relatively ``nearby'' objects, perhaps out to some hundred million lightyears. When we look much further into space, we also look far back in time and it is not excluded that the universal expansion rate, i.e. the Hubble constant, may have been different at earlier epochs. This means that unless we know the change of the Hubble constant with time, we cannot determine reliable distances of distant galaxies from their measured redshifts and velocities. At the same time, knowledge about such change or lack of the same will provide unique information about the time elapsed since the Universe began to expand (the ``Big Bang''), that is, the age of the Universe and also its ultimate fate. The Deceleration Parameter q0 Cosmologists are therefore eager to determine not only the current expansion rate (i.e., the Hubble constant, H0) but also its possible change with time (known as the deceleration parameter, q0). Although a highly accurate value of H0 has still not become available, increasing attention is now given to the observational determination of the second parameter, cf. also the Appendix at the

  12. HERG1 Channel Agonists and Cardiac Arrhythmia

    PubMed Central

    Sanguinetti, Michael

    2014-01-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  13. HERG1 channel agonists and cardiac arrhythmia.

    PubMed

    Sanguinetti, Michael C

    2014-04-01

    Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650

  14. Shock wave study of the thermal dissociations of C3F6 and c-C3F6. I. dissociation of hexafluoropropene.

    PubMed

    Cobos, C J; Sölter, L; Tellbach, E; Troe, J

    2014-07-10

    The thermal dissociation of C3F6 was studied between 1330 and 2210 K in shock waves monitoring the UV absorption of CF2. CF2 yields of about 2.6 per parent C3F6 were obtained at reactant concentrations of 500-1000 ppm in the bath gas Ar. These yields dropped to about 1.8 when reactant concentrations were lowered to 60 ppm. The increase of the CF2 yield with increasing concentration was attributed to bimolecular reactions between primary and secondary dissociation products. Quantum-chemical and kinetic modeling calculations helped to estimate the contributions from the various primary dissociation steps. It was shown that the measurements correspond to unimolecular reactions in their falloff range. Falloff representations of the rate constants are given, leading to an overall high pressure rate constant k∞ = 2.0 × 10(17)(-104 kcal mol(-1)/RT) s(-1) and a relative rate of about 2/3:1/3 for the reactions C3F6 → CF3CF + CF2 versus C3F6 → C2F3 + CF3. PMID:24905383

  15. Dissociation in virtual reality: depersonalization and derealization

    NASA Astrophysics Data System (ADS)

    Garvey, Gregory P.

    2010-01-01

    This paper looks at virtual worlds such as Second Life7 (SL) as possible incubators of dissociation disorders as classified by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition3 (also known as the DSM-IV). Depersonalization is where "a person feels that he or she has changed in some way or is somehow unreal." Derealization when "the same beliefs are held about one's surroundings." Dissociative Identity Disorder (DID), previously known as multiple personality disorder fits users of Second Life who adopt "in-world" avatars and in effect, enact multiple distinct identities or personalities (known as alter egos or alters). Select questions from the Structured Clinical Interview for Depersonalization (SCI-DER)8 will be discussed as they might apply to the user's experience in Second Life. Finally I would like to consider the hypothesis that rather than a pathological disorder, dissociation is a normal response to the "artificial reality" of Second Life.

  16. Electron Transfer Dissociation of Oligonucleotide Cations.

    PubMed

    Smith, Suncerae I; Brodbelt, Jennifer S

    2009-06-01

    Electron transfer dissociation (ETD) of multi-protonated 6 - 20-mer oligonucleotides and 12- and 14-mer duplexes is compared to collision activated dissociation (CAD). ETD causes efficient charge reduction of the multi-protonated oligonucleotides in addition to limited backbone cleavages to yield sequence ions of low abundance. Subsequent CAD of the charge-reduced oligonucleotides formed upon electron transfer, in a net process termed electron transfer collision activated dissociation (ETcaD), results in rich fragmentation in terms of w, a, z, and d products, with a marked decrease in the abundance of base loss ions and internal fragments. Complete sequencing was possible for nearly all oligonucleotides studied. ETcaD of an oligonucleotide duplex resulted in specific backbone cleavages, with conservation of weaker non-covalent bonds. PMID:20161288

  17. Psychotherapy and pharmacotherapy for patients with dissociative identity disorder.

    PubMed

    Gentile, Julie P; Dillon, Kristy S; Gillig, Paulette Marie

    2013-02-01

    There is a wide variety of what have been called "dissociative disorders," including dissociative amnesia, dissociative fugue, depersonalization disorder, dissociative identity disorder, and forms of dissociative disorder not otherwise specified. Some of these diagnoses, particularly dissociative identity disorder, are controversial and have been questioned by many clinicians over the years. The disorders may be under-diagnosed or misdiagnosed, but many persons who have experienced trauma report "dissociative" symptoms. Prevalence of dissociative disorders is unknown, but current estimates are higher than previously thought. This paper reviews clinical, phenomenological, and epidemiological data regarding diagnosis in general, and illustrates possible treatment interventions for dissociative identity disorder, with a focus on psychotherapy interventions and a review of current psychopharmacology recommendations as part of a comprehensive multidisciplinary treatment plan. PMID:23556139

  18. Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimer’s disease mouse model

    PubMed Central

    Kunath, Nicolas; van Groen, Thomas; Allison, David B.; Kumar, Ashish; Dozier-Sharpe, Monique; Kadish, Inga

    2015-01-01

    The orexigenic hormone ghrelin, a potential antagonist of the insulin system, ensures sufficient serum glucose in times of fasting. In the race for new therapeutics for diabetes, one focus of study has been antagonizing the ghrelin system in order to improve glucose tolerance. We provide evidence for a differential role of a ghrelin agonist on glucose homeostasis in an Alzheimer’s disease mouse model fed a high–glycemic index diet as a constant challenge for glucose homeostasis. The ghrelin agonist impaired glucose tolerance immediately after administration but not in the long term. At the same time, the ghrelin agonist improved spatial learning in the mice, raised their activity levels, and reduced their body weight and fat mass. Immunoassay results showed a beneficial impact of long-term treatment on insulin signaling pathways in hippocampal tissue. The present results suggest that ghrelin might improve cognition in Alzheimer’s disease via a central nervous system mechanism involving insulin signaling. PMID:26090621

  19. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-01

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID:26832440

  20. Melanocortin 1 Receptor Agonists Reduce Proteinuria

    PubMed Central

    Ebefors, Kerstin; Johansson, Martin E.; Stefánsson, Bergur; Granqvist, Anna; Arnadottir, Margret; Berg, Anna-Lena; Nyström, Jenny; Haraldsson, Börje

    2010-01-01

    Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown. Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients. PMID:20507942

  1. Kinetics of Propargyl Radical Dissociation.

    PubMed

    Klippenstein, Stephen J; Miller, James A; Jasper, Ahren W

    2015-07-16

    Due to the prominent role of the propargyl radical for hydrocarbon growth within combustion environments, it is important to understand the kinetics of its formation and loss. The ab initio transition state theory-based master equation method is used to obtain theoretical kinetic predictions for the temperature and pressure dependence of the thermal decomposition of propargyl, which may be its primary loss channel under some conditions. The potential energy surface for the decomposition of propargyl is first mapped at a high level of theory with a combination of coupled cluster and multireference perturbation calculations. Variational transition state theory is then used to predict the microcanonical rate coefficients, which are subsequently implemented within the multiple-well multiple-channel master equation. A variety of energy transfer parameters are considered, and the sensitivity of the thermal rate predictions to these parameters is explored. The predictions for the thermal decomposition rate coefficient are found to be in good agreement with the limited experimental data. Modified Arrhenius representations of the rate constants are reported for utility in combustion modeling. PMID:25871530

  2. Dissociation of ultracold molecules with Feshbach resonances

    SciTech Connect

    Duerr, Stephan; Volz, Thomas; Rempe, Gerhard

    2004-09-01

    Ultracold molecules are associated from an atomic Bose-Einstein condensate by ramping a magnetic field across a Feshbach resonance. The reverse ramp dissociates the molecules. The kinetic energy released in the dissociation process is used to measure the widths of four Feshbach resonances in {sup 87}Rb. This method to determine the width works remarkably well for narrow resonances even in the presence of significant magnetic-field noise. In addition, a quasimonoenergetic atomic wave is created by jumping the magnetic field across the Feshbach resonance.

  3. Dissociation and recombination in an inhomogeneous gas

    NASA Astrophysics Data System (ADS)

    Kuščer, Ivan

    1991-09-01

    The system of Boltzmann equations of Ludwig and Heil for a dissociating gas mixture is reviewed and reformulated in terms of differential cross sections. For the purpose of Monte Carlo simulations, collision models of the type of Borgnakke and Larsen are proposed. In case of short-lived transient flows of molecular gases and at not too high temperatures, simulation of scattering collisions is expected to suffice; the distribution function of the dissociated particles can be evaluated afterwards by integration, and recombination can be ignored.

  4. Quantum Zeno control of coherent dissociation

    SciTech Connect

    Khripkov, C.; Vardi, A.

    2011-08-15

    We study the effect of dephasing on the coherent dissociation dynamics of an atom-molecule Bose-Einstein condensate. We show that when phase-noise intensity is strong with respect to the inverse correlation time of the stimulated process, dissociation is suppressed via a Bose enhanced quantum Zeno effect. This is complementary to the quantum Zeno control of phase-diffusion in a bimodal condensate by symmetric noise [Phys. Rev. Lett. 100, 220403 (2008)] in that the controlled process here is phase formation and the required decoherence mechanism for its suppression is purely phase noise.

  5. Differential Signaling of the Endogenous Agonists at the β2-Adrenergic Receptor*

    PubMed Central

    Reiner, Susanne; Ambrosio, Manuela; Hoffmann, Carsten; Lohse, Martin J.

    2010-01-01

    The concept of “functional selectivity” or “biased signaling” suggests that a ligand can have distinct efficacies with regard to different signaling pathways. We have investigated the question of whether biased signaling may be related to distinct agonist-induced conformational changes in receptors using the β2-adrenergic receptor (β2AR) and its two endogenous ligands epinephrine and norepinephrine as a model system. Agonist-induced conformational changes were determined in a fluorescently tagged β2AR FRET sensor. In this β2AR sensor, norepinephrine caused signals that amounted to only ≈50% of those induced by epinephrine and the standard “full” agonist isoproterenol. Furthermore, norepinephrine-induced changes in the β2AR FRET sensor were slower than those induced by epinephrine (rate constants, 47 versus 128 ms). A similar partial β2AR activation signal was revealed for the synthetic agonists fenoterol and terbutaline. However, norepinephrine was almost as efficient as epinephrine (and isoproterenol) in causing activation of Gs and adenylyl cyclase. In contrast, fenoterol was quite efficient in triggering β-arrestin2 recruitment to the cell surface and its interaction with β2AR, as well as internalization of the receptors, whereas norepinephrine caused partial and slow changes in these assays. We conclude that partial agonism of norepinephrine at the β2AR is related to the induction of a different active conformation and that this conformation is efficient in signaling to Gs and less efficient in signaling to β-arrestin2. These observations extend the concept of biased signaling to the endogenous agonists of the β2AR and link it to distinct conformational changes in the receptor. PMID:20837485

  6. Desensitization of human CRF2(a) receptor signaling governed by agonist potency and βarrestin2 recruitment.

    PubMed

    Hauger, Richard L; Olivares-Reyes, J Alberto; Braun, Sandra; Hernandez-Aranda, Judith; Hudson, Christine C; Gutknecht, Eric; Dautzenberg, Frank M; Oakley, Robert H

    2013-09-10

    The primary goal was to determine agonist-specific regulation of CRF2(a) receptor function. Exposure of human retinoblastoma Y79 cells to selective (UCN2, UCN3 or stresscopins) and non-selective (UCN1 or sauvagine) agonists prominently desensitized CRF2(a) receptors in a rapid, concentration-dependent manner. A considerably slower rate and smaller magnitude of desensitization developed in response to the weak agonist CRF. CRF1 receptor desensitization stimulated by CRF, cortagine or stressin1-A had no effect on CRF2(a) receptor cyclic AMP signaling. Conversely, desensitization of CRF2(a) receptors by UCN2 or UCN3 did not cross-desensitize Gs-coupled CRF1 receptor signaling. In transfected HEK293 cells, activation of CRF2(a) receptors by UCN2, UCN3 or CRF resulted in receptor phosphorylation and internalization proportional to agonist potency. Neither protein kinase A nor casein kinases mediated CRF2(a) receptor phosphorylation or desensitization. Exposure of HEK293 or U2OS cells to UCN2 or UCN3 (100nM) produced strong βarrestin2 translocation and colocalization with membrane CRF2(a) receptors while CRF (1μM) generated only weak βarrestin2 recruitment. βarrestin2 did not internalize with the receptor, however, indicating that transient CRF2(a) receptor-arrestin complexes dissociate at or near the cell membrane. Since deletion of the βarrestin2 gene upregulated Gs-coupled CRF2(a) receptor signaling in MEF cells, a βarrestin2 mechanism restrains Gs-coupled CRF2(a) receptor signaling activated by urocortins. We further conclude that the rate and extent of homologous CRF2(a) receptor desensitization are governed by agonist-specific mechanisms affecting GRK phosphorylation, βarrestin2 recruitment, and internalization thereby producing unique signal transduction profiles that differentially affect the stress response. PMID:23820308

  7. Carbon monoxide dissociative attachment and resonant dissociation by electron-impact

    NASA Astrophysics Data System (ADS)

    Laporta, V.; Tennyson, J.; Celiberto, R.

    2016-02-01

    Low-energy dissociative electron attachment and resonant electron impact dissociation of CO molecule are considered. Ro-vibrationally resolved cross sections and rate coefficients for both the processes are calculated using an ab-initio model based on the low-lying \\text{X}{{}2}\\Pi resonance of CO-. Final results show that the cross sections increases very rapidly as a function of the ro-vibrational level; these cross sections should be useful for understanding kinetic dissociation of CO in strongly non-equilibrium plasmas.

  8. Isotherm-Based Thermodynamic Models for Solute Activities of Organic Acids with Consideration of Partial Dissociation.

    PubMed

    Nandy, Lucy; Ohm, Peter B; Dutcher, Cari S

    2016-06-23

    Organic acids make up a significant fraction of the organic mass in atmospheric aerosol particles. The calculation of gas-liquid-solid equilibrium partitioning of the organic acid is therefore critical for accurate determination of atmospheric aerosol physicochemical properties and processes such as new particle formation and activation to cloud condensation nuclei. Previously, an adsorption isotherm-based statistical thermodynamic model was developed for capturing solute concentration-activity relationships for multicomponent aqueous solutions over the entire concentration range (Dutcher et al. J. Phys. Chem. C/A 2011, 2012, 2013), with model parameters for energies of adsorption successfully related to dipole-dipole electrostatic forces in solute-solvent and solvent-solvent interactions for both electrolytes and organics (Ohm et al. J. Phys. Chem. A 2015). However, careful attention is needed for weakly dissociating semivolatile organic acids. Dicarboxylic acids, such as malonic acid and glutaric acid are treated here as a mixture of nondissociated organic solute (HA) and dissociated solute (H(+) + A(-)). It was found that the apparent dissociation was greater than that predicted by known dissociation constants alone, emphasizing the effect of dissociation on osmotic and activity coefficient predictions. To avoid additional parametrization from the mixture approach, an expression was used to relate the Debye-Hückel hard-core collision diameter to the adjustable solute-solvent intermolecular distance. An improved reference state treatment for electrolyte-organic aqueous mixtures, such as that observed here with partial dissociation, has also been proposed. This work results in predictive correlations for estimation of organic acid and water activities for which there is little or no activity data. PMID:27222917

  9. New Quasar Studies Keep Fundamental Physical Constant Constant

    NASA Astrophysics Data System (ADS)

    2004-03-01

    Very Large Telescope sets stringent limit on possible variation of the fine-structure constant over cosmological time Summary Detecting or constraining the possible time variations of fundamental physical constants is an important step toward a complete understanding of basic physics and hence the world in which we live. A step in which astrophysics proves most useful. Previous astronomical measurements of the fine structure constant - the dimensionless number that determines the strength of interactions between charged particles and electromagnetic fields - suggested that this particular constant is increasing very slightly with time. If confirmed, this would have very profound implications for our understanding of fundamental physics. New studies, conducted using the UVES spectrograph on Kueyen, one of the 8.2-m telescopes of ESO's Very Large Telescope array at Paranal (Chile), secured new data with unprecedented quality. These data, combined with a very careful analysis, have provided the strongest astronomical constraints to date on the possible variation of the fine structure constant. They show that, contrary to previous claims, no evidence exist for assuming a time variation of this fundamental constant. PR Photo 07/04: Relative Changes with Redshift of the Fine Structure Constant (VLT/UVES) A fine constant To explain the Universe and to represent it mathematically, scientists rely on so-called fundamental constants or fixed numbers. The fundamental laws of physics, as we presently understand them, depend on about 25 such constants. Well-known examples are the gravitational constant, which defines the strength of the force acting between two bodies, such as the Earth and the Moon, and the speed of light. One of these constants is the so-called "fine structure constant", alpha = 1/137.03599958, a combination of electrical charge of the electron, the Planck constant and the speed of light. The fine structure constant describes how electromagnetic forces hold

  10. Double Dissociation between Reading and Spelling Deficits

    ERIC Educational Resources Information Center

    Moll, Kristina; Landerl, Karin

    2009-01-01

    In two studies dissociations between reading and spelling skills were examined. Study 1 reports equally high prevalence rates for isolated deficits in reading (7%) or spelling (6%) in a representative sample (N = 2,029) of German-speaking elementary school children. In Study 2, children with isolated deficits were presented with the same words to…

  11. EVIDENCE FOR CO DISSOCIATION ON RHODIUM SURFACES

    SciTech Connect

    Castner, D.G.; Dubois, L.H.; Sexton, B.A.; Somorjai, G.A.

    1980-06-01

    Carbon monoxide adsorbs molecularly on rhodium surfaces at 300K, but if the rhodium samples are heated in the presence of carbon monoxide, there is evidence for carbon-oxygen bond breaking at step and/or defect sites. The effects of step and defect site density, subsurface oxygen concentration, and oxygen dissolution into the rhodium lattice on CO dissociation are discussed.

  12. Phenyl radical thermolysis and rate constants for phenyl + O{sub 2}

    SciTech Connect

    Kumaran, S.S.; Michael, J.V.

    1997-08-01

    The thermal decomposition of C{sub 6}H{sub 5}I has been used to prepare in-situ known initial concentrations of phenyl radicals at high temperatures. These can be degraded by direct decomposition at T > 1350 K giving H + C{sub 6}H{sub 4}. Using H-atom ARAS, rate constants for C{sub 6}H{sub 5} dissociation have been measured. Using the same ARAS technique, constants for C{sub 6}H{sub 5} dissociation have been measured. Using the same ARAS technique, the H- and O-atoms formed from the reaction, C{sub 6}H{sub 5} + O{sub 2}, have both been measured. The rate constant results are discussed along with lower T measurements in terms of RRKM calculations using published ab initio electronic structure determinations of transition states.

  13. Thermal dissociation behavior and dissociation enthalpies of methane-carbon dioxide mixed hydrates

    SciTech Connect

    Kwon, T.H.; Kneafsey, T.J.; Rees, E.V.L.

    2011-02-15

    Replacement of methane with carbon dioxide in hydrate has been proposed as a strategy for geologic sequestration of carbon dioxide (CO{sub 2}) and/or production of methane (CH{sub 4}) from natural hydrate deposits. This replacement strategy requires a better understanding of the thermodynamic characteristics of binary mixtures of CH{sub 4} and CO{sub 2} hydrate (CH{sub 4}-CO{sub 2} mixed hydrates), as well as thermophysical property changes during gas exchange. This study explores the thermal dissociation behavior and dissociation enthalpies of CH{sub 4}-CO{sub 2} mixed hydrates. We prepared CH{sub 4}-CO{sub 2} mixed hydrate samples from two different, well-defined gas mixtures. During thermal dissociation of a CH{sub 4}-CO{sub 2} mixed hydrate sample, gas samples from the head space were periodically collected and analyzed using gas chromatography. The changes in CH{sub 4}-CO{sub 2} compositions in both the vapor phase and hydrate phase during dissociation were estimated based on the gas chromatography measurements. It was found that the CO{sub 2} concentration in the vapor phase became richer during dissociation because the initial hydrate composition contained relatively more CO{sub 2} than the vapor phase. The composition change in the vapor phase during hydrate dissociation affected the dissociation pressure and temperature; the richer CO{sub 2} in the vapor phase led to a lower dissociation pressure. Furthermore, the increase in CO{sub 2} concentration in the vapor phase enriched the hydrate in CO{sub 2}. The dissociation enthalpy of the CH{sub 4}-CO{sub 2} mixed hydrate was computed by fitting the Clausius-Clapeyron equation to the pressure-temperature (PT) trace of a dissociation test. It was observed that the dissociation enthalpy of the CH{sub 4}-CO{sub 2} mixed hydrate lays between the limiting values of pure CH{sub 4} hydrate and CO{sub 2} hydrate, increasing with the CO{sub 2} fraction in the hydrate phase.

  14. Psychotherapy and Pharmacotherapy for Patients with Dissociative Identity Disorder

    PubMed Central

    Gentile, Julie P.; Dillon, Kristy S.

    2013-01-01

    There is a wide variety of what have been called “dissociative disorders,” including dissociative amnesia, dissociative fugue, depersonalization disorder, dissociative identity disorder, and forms of dissociative disorder not otherwise specified. Some of these diagnoses, particularly dissociative identity disorder, are controversial and have been questioned by many clinicians over the years. The disorders may be under-diagnosed or misdiagnosed, but many persons who have experienced trauma report “dissociative” symptoms. Prevalence of dissociative disorders is unknown, but current estimates are higher than previously thought. This paper reviews clinical, phenomenological, and epidemiological data regarding diagnosis in general, and illustrates possible treatment interventions for dissociative identity disorder, with a focus on psychotherapy interventions and a review of current psychopharmacology recommendations as part of a comprehensive multidisciplinary treatment plan. PMID:23556139

  15. Force and Stress along Simulated Dissociation Pathways of Cucurbituril-Guest Systems

    PubMed Central

    Velez-Vega, Camilo; Gilson, Michael K.

    2012-01-01

    The field of host-guest chemistry provides computationally tractable yet informative model systems for biomolecular recognition. We applied molecular dynamics simulations to study the forces and mechanical stresses associated with forced dissociation of aqueous cucurbituril-guest complexes with high binding affinities. First, the unbinding transitions were modeled with constant velocity pulling (steered dynamics) and a soft spring constant, to model atomic force microscopy (AFM) experiments. The computed length-force profiles yield rupture forces in good agreement with available measurements. We also used steered dynamics with high spring constants to generate paths characterized by a tight control over the specified pulling distance; these paths were then equilibrated via umbrella sampling simulations and used to compute time-averaged mechanical stresses along the dissociation pathways. The stress calculations proved to be informative regarding the key interactions determining the length-force profiles and rupture forces. In particular, the unbinding transition of one complex is found to be a stepwise process, which is initially dominated by electrostatic interactions between the guest’s ammoniums and the host’s carbonyl groups, and subsequently limited by the extraction of the guest’s bulky bicyclooctane moiety; the latter step requires some bond stretching at the cucurbituril’s extraction portal. Conversely, the dissociation of a second complex with a more slender guest is mainly driven by successive electrostatic interactions between the different guest’s ammoniums and the host’s carbonyl groups. The calculations also provide information on the origins of thermodynamic irreversibilities in these forced dissociation processes. PMID:22754402

  16. Exposure of MC4R to agonist in the endoplasmic reticulum stabilizes an active conformation of the receptor that does not desensitize

    PubMed Central

    Granell, Susana; Molden, Brent M.; Baldini, Giulia

    2013-01-01

    Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in neurons of the hypothalamus where it regulates food intake. MC4R responds to an agonist, α-melanocyte–stimulating hormone (α-MSH) and to an antagonist/inverse agonist, agouti-related peptide (AgRP), which are released by upstream neurons. Binding to α-MSH leads to stimulation of receptor activity and suppression of food intake, whereas AgRP has opposite effects. MC4R cycles constantly between the plasma membrane and endosomes and undergoes agonist-mediated desensitization by being routed to lysosomes. MC4R desensitization and increased AgRP expression are thought to decrease the effectiveness of MC4R agonists as an antiobesity treatment. In this study, α-MSH, instead of being delivered extracellularly, is targeted to the endoplasmic reticulum (ER) of neuronal cells and cultured hypothalamic neurons. We find that the ER-targeted agonist associates with MC4R at this location, is transported to the cell surface, induces constant cAMP and AMP kinase signaling at maximal amplitude, abolishes desensitization of the receptor, and promotes both cell-surface expression and constant signaling by an obesity-linked MC4R variant, I316S, that otherwise is retained in the ER. Formation of the MC4R/agonist complex in the ER stabilizes the receptor in an active conformation that at the cell surface is insensitive to antagonism by AgRP and at the endosomes is refractory to routing to the lysosomes. The data indicate that targeting agonists to the ER can stabilize an active conformation of a G protein-coupled receptor that does not become desensitized, suggesting a target for therapy. PMID:24248383

  17. What contributes to predicting change in the treatment of dissociation: initial levels of dissociation, PTSD, or overall distress?

    PubMed

    Brand, Bethany L; Stadnik, Ryan

    2013-01-01

    Individuals with dissociative disorders (DDs) suffer from high levels of dissociation as well as posttraumatic stress disorder (PTSD) and general distress. No research has investigated how changes in dissociation relate to changes in other symptoms over the course of treatment in patients with DD. Using a prospective, naturalistic design, we collected reports of symptoms from a sample of therapists and their patients diagnosed with dissociative identity disorder or dissociative disorder not otherwise specified who participated in the Treatment Outcome of Patients with Dissociative Disorders study. The patients completed surveys at intake (Time 1) into the study and at 30-month follow-up (Time 4). We found that dissociative symptoms, including amnesia, depersonalization/derealization, and absorption, at the initial assessment of the study ("initial") were related to initial levels of PTSD and general distress and that changes in dissociative symptoms were related to changes in PTSD and general distress. Initial dissociation was a significant predictor of change in dissociation at 30 months when we controlled for length of time for follow-up, length of time practicing therapy, and length of time treating dissociative patients. Our results suggest that a reduction in dissociative symptoms in DD patients is associated with reductions in the overall severity of dissociative, posttraumatic stress, and distress symptoms. PMID:23627481

  18. Dissociation of acetaldehyde in intense laser field: Coulomb explosion or field-assisted dissociation?

    NASA Astrophysics Data System (ADS)

    Elshakre, Mohamed E.; Gao, Lirong; Tang, Xiaoping; Wang, Sufan; Shu, Yafei; Kong, Fanao

    2003-09-01

    Dissociation of acetaldehyde in moderate strong laser field of 1013-1014W/cm2 was investigated. Singly charged parent ion CH3CHO+ and fragmental ions CH3+, CHO+, C2H4+, O+, CH2CHO+, and H+ were produced by 800 nm laser of 100 fs pulse duration and recorded by time-of-flight mass spectrometer. The CH3+ fragment further dissociated to CH2+, CH+, and C+ ions at higher intensity. Ab initio calculated results show that the singly-, doubly-, and triply charged parent ions are stable. So, the dissociation mechanism was not due to Coulomb explosion of multicharged ion. A field-assisted dissociation (FAD) theory, which assumes that only one bond undergoes dissociation while the rest of the molecular geometry stays unchanged, was employed to treat the dissociation dynamics. Accordingly, the dressed potential energy surfaces of the ground state for the parent and the fragment ions were calculated. Corresponding quasiclassical trajectory calculations show that the bond ruptures take place in the order of C-C, C-O, and C-H, agreeing with the observation. The observed angular dependence and charge distribution of the product ions can also be interpreted by the FAD theory.

  19. Does phasic trauma treatment make patients with dissociative identity disorder treatment more dissociative?

    PubMed

    Brand, Bethany; Loewenstein, Richard J

    2014-01-01

    Proponents of the iatrogenic model of the etiology of dissociative identity disorder (DID) have expressed concern that treatment focused on direct engagement and interaction with dissociated self-states harms DID patients. However, empirical data have shown that this type of DID treatment is beneficial. Analyzing data from the prospective Treatment of Patients With Dissociative Disorders (TOP DD) Study, we test empirically whether DID treatment is associated with clinically adverse manifestations of dissociated self-states: acting so differently that one feels like different people, hearing voices, and dissociative amnesia. We show that, over the course of the study, there were significant decreases in feeling like different people and hearing voices. These results indicate that this form of DID treatment does not lead to symptomatic worsening in these dimensions, as predicted by the iatrogenic model. Indeed, treatment provided by TOP DD therapists reduced, rather than increased, the extent to which patients experienced manifestations of pathological dissociation. Because severe symptomatology and impairment are associated with DID, iatrogenic harm may come from depriving DID patients of treatment that targets DID symptomatology. PMID:24377972

  20. In-Vacuum Dissociator for Atomic-Hydrogen Masers

    NASA Technical Reports Server (NTRS)

    Vessot, R. F.

    1987-01-01

    Thermal control and vacuum sealing achieved while contamination avoided. Simple, relatively inexpensive molecular-hydrogen dissociator for atomic-hydrogen masers used on Earth or in vacuum of space. No air cooling required, and absence of elastomeric O-ring seals prevents contamination. In-vacuum dissociator for atomic hydrogen masers, hydrogen gas in glass dissociator dissociated by radio-frequency signal transmitted from surrounding 3-turn coil. Heat in glass conducted away by contacting metal surfaces.

  1. Dopamine agonist: pathological gambling and hypersexuality.

    PubMed

    2008-10-01

    (1) Pathological gambling and increased sexual activity can occur in patients taking dopaminergic drugs. Detailed case reports and small case series mention serious familial and social consequences. The frequency is poorly documented; (2) Most affected patients are being treated for Parkinson's disease, but cases have been reported among patients prescribed a dopamine agonist for restless legs syndrome or pituitary adenoma; (3) Patients treated with this type of drug, and their relatives, should be informed of these risks so that they can watch for changes in behaviour. If such disorders occur, it may be necessary to reduce the dose or to withdraw the drug or replace it with another medication. PMID:19536937

  2. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  3. Mechanisms of agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Lin, Hong; Strange, Philip G

    2004-12-01

    In this study, we investigated the biochemical mechanisms of agonist action at the G protein-coupled D2 dopamine receptor expressed in Chinese hamster ovary cells. Stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding by full and partial agonists was determined at different concentrations of [35S]GTPgammaS (0.1 and 10 nM) and in the presence of different concentrations of GDP. At both concentrations of [35S]GTPgammaS, increasing GDP decreased the [35S]GTPgammaS binding observed with maximally stimulating concentrations of agonist, with partial agonists exhibiting greater sensitivity to the effects of GDP than full agonists. The relative efficacy of partial agonists was greater at the lower GDP concentrations. Concentration-response experiments were performed for a range of agonists at the two [35S]GTPgammaS concentrations and with different concentrations of GDP. At 0.1 nM [35S]GTPgammaS, the potency of both full and partial agonists was dependent on the GDP concentration in the assays. At 10 nM [35S]GTPgammaS, the potency of full agonists exhibited a greater dependence on the GDP concentration, whereas the potency of partial agonists was virtually independent of GDP. We concluded that at the lower [35S]GTPgammaS concentration, the rate-determining step in G protein activation is the binding of [35S]GTPgammaS to the G protein. At the higher [35S]GTPgammaS concentration, for full agonists, [35S]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining. PMID:15340043

  4. Derivatives of imidopyrophosphoric acids as extractants. Part I. The preparation and fundamental constants of tetraalkylimidopyrophosphoric acids

    SciTech Connect

    Preez, J.G.H. du; Knabl, K.U.; Krueger, L.; Brecht, B.J.A.M. van )

    1992-12-01

    Improved methods for the preparation of imidotetraalkylpyrophosphates are reported. The dissociation constant of the water soluble tetraethyl analogue was determined by potentiometric titration. The values for the partition constant and aggregation constant of the tetradodecyl analogue were determined by two phase EMF potentiometric titration of which the data were processed through a sophisticated general optimization technique. The application of this method also made it possible to obtain a species distribution curve of the organic phase in terms of variation of pH in the aqueous phase. 17 refs., 7 figs., 4 tabs.

  5. Self-consistent-field treatment of the dissociation of bound molecules in solution

    NASA Astrophysics Data System (ADS)

    Galindo, Carlos E.; Sokoloff, J. B.

    1993-10-01

    We present calculations of the dissociation of hydrogen-bonded molecules in solution, using a mean-field theory based on a variational method [N.R. Werthamer, in Rare Gas Solids, edited by M. L. Klein and J. A. Venables (Academic, New York, 1976), Vol. I, Chap. V]. The solvent is accounted for by a dielectric constant, and the effect of salt ions in solution on hydrogen bonding is treated by means of Soumpasis's potential of mean force [D. M. Soumpasis, Proc. Natl. Acad. Sci. USA 81, 5116 (1984)]. At high concentrations, the effect of salt ions on the interaction is dominated by an effective temperature-dependent interaction, which results from a position-dependent term in the entropy resulting from the hard-core volume exclusion. In addition to describing the dissociation transition, this procedure provides the temperature and electrolyte-concentration dependence of the vibrational spectrum. The sample calculation by Gao and Prohofsky [J. Chem. Phys. 80, 2242 (1984)] of two ammonia molecules bound together by a hydrogen bond in a vacuum is reconsidered in an ionic solution. Our method is also applied to the treatment of the hydrogen-bond dissociation of a pair of water molecules and of a hydrogen-bonded pair of negative point-charge ions. The latter is intended as a simple model for the dissociation of a single hydrogen-bonded base-pair unit of a DNA double helix.

  6. Dissociation quotient of benzoic acid in aqueous sodium chloride media to 250{degrees}C

    SciTech Connect

    Kettler, R.M.; Palmer, D.A.; Wesolowski, D.J.

    1995-04-01

    The dissociation quotient of benzoic acid was determined potentiometrically in a concentration cell fitted with hydrogen electrodes. The hydrogen ion molality of benzoic acid/benzoate solutions was measured relative to a standard aqueous HCl solution at seven temperatures from 5 to 250{degrees}C and at seven ionic strengths ranging from 0.1 to 5.0 molal (NaCl). The molal dissociation quotients and selected literature data were fitted in the isocoulombic (all anionic) form by a six-term equation. This treatment yielded the following thermodynamic quantities for the acid dissociation equilibrium at 25{degrees}C and 1 bar: logK{sub a} = -4.206{+-}0.006, {Delta}H{sub a}{sup 0} = 0.3{+-}0.3 kJ-mol{sup {minus}1}, {Delta}S{sub a}{sup 0} = -79.6{+-}1.0 J-mol{sup {minus}1}-K{sup {minus}1}, and {Delta}C{sub p;a}{sup 0} = -207{+-}5 J-mol{sup {minus}1}-K{sup {minus}1}. A five-term equation derived to describe the dependence of the dissociation constant on solvent density is accurate to 250{degrees}C and 200 MPa.

  7. Salinity-buffered methane hydrate formation and dissociation in gas-rich systems

    NASA Astrophysics Data System (ADS)

    You, Kehua; Kneafsey, Timothy J.; Flemings, Peter B.; Polito, Peter; Bryant, Steven L.

    2015-02-01

    Methane hydrate formation and dissociation are buffered by salinity in a closed system. During hydrate formation, salt excluded from hydrate increases salinity, drives the system to three-phase (gas, water, and hydrate phases) equilibrium, and limits further hydrate formation and dissociation. We developed a zero-dimensional local thermodynamic equilibrium-based model to explain this concept. We demonstrated this concept by forming and melting methane hydrate from a partially brine-saturated sand sample in a controlled laboratory experiment by holding pressure constant (6.94 MPa) and changing temperature stepwise. The modeled methane gas consumptions and hydrate saturations agreed well with the experimental measurements after hydrate nucleation. Hydrate dissociation occurred synchronously with temperature increase. The exception to this behavior is that substantial subcooling (6.4°C in this study) was observed for hydrate nucleation. X-ray computed tomography scanning images showed that core-scale hydrate distribution was heterogeneous. This implied core-scale water and salt transport induced by hydrate formation. Bulk resistivity increased sharply with initial hydrate formation and then decreased as the hydrate ripened. This study reproduced the salinity-buffered hydrate behavior interpreted for natural gas-rich hydrate systems by allowing methane gas to freely enter/leave the sample in response to volume changes associated with hydrate formation and dissociation. It provides insights into observations made at the core scale and log scale of salinity elevation to three-phase equilibrium in natural hydrate systems.

  8. Effects of thermodynamic inhibitors on the dissociation of methane hydrate: a molecular dynamics study.

    PubMed

    Yagasaki, Takuma; Matsumoto, Masakazu; Tanaka, Hideki

    2015-12-28

    We investigate the effects of methanol and NaCl, which are known as thermodynamic hydrate inhibitors, on the dissociation kinetics of methane hydrate in aqueous solutions by using molecular dynamics simulations. It is shown that the dissociation rate is not constant but changes with time. The dissociation rate in the initial stage is increased by methanol whereas it is decreased by NaCl. This difference arises from the opposite effects of the two thermodynamic inhibitors on the hydration free energy of methane. The dissociation rate of methane hydrate is increased by the formation of methane bubbles in the aqueous phase because the bubbles absorb surrounding methane molecules. It is found that both methanol and NaCl facilitate the bubble formation. However, their mechanisms are completely different from each other. The presence of ions enhances the hydrophobic interactions between methane molecules. In addition, the ions in the solution cause a highly non-uniform distribution of dissolved methane molecules. These two effects result in the easy formation of bubbles in the NaCl solution. In contrast, methanol assists the bubble formation because of its amphiphilic character. PMID:26587576

  9. Formulas for determining rotational constants

    NASA Astrophysics Data System (ADS)

    Guelachvili, G.

    This document is part of Subvolume B `Linear Triatomic Molecules', Part 9, of Volume 20 `Molecular Constants mostly from Infrared Spectroscopy' of Landolt-Börnstein Group II `Molecules and Radicals'. Part of the introduction, it states formulas for determining rotational constants, band center, band origin, and quadrupole coupling. Specific comments relate to BHO (HBO) and COS (OCS).

  10. QCD coupling constants and VDM

    SciTech Connect

    Erkol, G.; Ozpineci, A.; Zamiralov, V. S.

    2012-10-23

    QCD sum rules for coupling constants of vector mesons with baryons are constructed. The corresponding QCD sum rules for electric charges and magnetic moments are also derived and with the use of vector-meson-dominance model related to the coupling constants. The VDM role as the criterium of reciprocal validity of the sum rules is considered.

  11. Cognitive Processes in Dissociation: Comment on Giesbrecht et al. (2008)

    ERIC Educational Resources Information Center

    Bremner, J. Douglas

    2010-01-01

    In their recent review "Cognitive Processes in Dissociation: An Analysis of Core Theoretical Assumptions," published in "Psychological Bulletin", Giesbrecht, Lynn, Lilienfeld, and Merckelbach (2008) have challenged the widely accepted trauma theory of dissociation, which holds that dissociative symptoms are caused by traumatic stress. In doing so,…

  12. 21 CFR 886.1910 - Spectacle dissociation test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Spectacle dissociation test system. 886.1910... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1910 Spectacle dissociation test system. (a) Identification. A spectacle dissociation test system is an AC-powered or...

  13. 21 CFR 886.1910 - Spectacle dissociation test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Spectacle dissociation test system. 886.1910... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1910 Spectacle dissociation test system. (a) Identification. A spectacle dissociation test system is an AC-powered or...

  14. 21 CFR 886.1910 - Spectacle dissociation test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Spectacle dissociation test system. 886.1910... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1910 Spectacle dissociation test system. (a) Identification. A spectacle dissociation test system is an AC-powered or...

  15. 21 CFR 886.1910 - Spectacle dissociation test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Spectacle dissociation test system. 886.1910... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1910 Spectacle dissociation test system. (a) Identification. A spectacle dissociation test system is an AC-powered or...

  16. Development, Reliability, and Validity of a Child Dissociation Scale.

    ERIC Educational Resources Information Center

    Putnam, Frank W.; And Others

    1993-01-01

    Evaluation of the Child Dissociative Checklist found it to be a reliable and valid observer report measure of dissociation in children, including sexually abused girls and children with dissociative disorder and with multiple personality disorder. The checklist, which is appended, is intended as a clinical screening instrument and research measure…

  17. Speech-Language Dissociations, Distractibility, and Childhood Stuttering

    PubMed Central

    Conture, Edward G.; Walden, Tedra A.; Lambert, Warren E.

    2015-01-01

    Purpose This study investigated the relation among speech-language dissociations, attentional distractibility, and childhood stuttering. Method Participants were 82 preschool-age children who stutter (CWS) and 120 who do not stutter (CWNS). Correlation-based statistics (Bates, Appelbaum, Salcedo, Saygin, & Pizzamiglio, 2003) identified dissociations across 5 norm-based speech-language subtests. The Behavioral Style Questionnaire Distractibility subscale measured attentional distractibility. Analyses addressed (a) between-groups differences in the number of children exhibiting speech-language dissociations; (b) between-groups distractibility differences; (c) the relation between distractibility and speech-language dissociations; and (d) whether interactions between distractibility and dissociations predicted the frequency of total, stuttered, and nonstuttered disfluencies. Results More preschool-age CWS exhibited speech-language dissociations compared with CWNS, and more boys exhibited dissociations compared with girls. In addition, male CWS were less distractible than female CWS and female CWNS. For CWS, but not CWNS, less distractibility (i.e., greater attention) was associated with more speech-language dissociations. Last, interactions between distractibility and dissociations did not predict speech disfluencies in CWS or CWNS. Conclusions The present findings suggest that for preschool-age CWS, attentional processes are associated with speech-language dissociations. Future investigations are warranted to better understand the directionality of effect of this association (e.g., inefficient attentional processes → speech-language dissociations vs. inefficient attentional processes ← speech-language dissociations). PMID:26126203

  18. Cognitive Processes in Dissociation: An Analysis of Core Theoretical Assumptions

    ERIC Educational Resources Information Center

    Giesbrecht, Timo; Lilienfield, Scott O.; Lynn, Steven Jay; Merckelbach, Harald

    2008-01-01

    Dissociation is typically defined as the lack of normal integration of thoughts, feelings, and experiences into consciousness and memory. The present article critically evaluates the research literature on cognitive processes in dissociation. The authors' review indicates that dissociation is characterized by subtle deficits in neuropsychological…

  19. MDMA, cannabis, and cocaine produce acute dissociative symptoms.

    PubMed

    van Heugten-Van der Kloet, Dalena; Giesbrecht, Timo; van Wel, Janelle; Bosker, Wendy M; Kuypers, Kim P C; Theunissen, Eef L; Spronk, Desirée B; Jan Verkes, Robbert; Merckelbach, Harald; Ramaekers, Johannes G

    2015-08-30

    Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology. PMID:26003508

  20. Prediction of Rate Constant for Supramolecular Systems with Multiconfigurations.

    PubMed

    Guo, Tao; Li, Haiyan; Wu, Li; Guo, Zhen; Yin, Xianzhen; Wang, Caifen; Sun, Lixin; Shao, Qun; Gu, Jingkai; York, Peter; Zhang, Jiwen

    2016-02-25

    The control of supramolecular systems requires a thorough understanding of their dynamics, especially on a molecular level. It is extremely difficult to determine the thermokinetic parameters of supramolecular systems, such as drug-cyclodextrin complexes with fast association/dissociation processes by experimental techniques. In this paper, molecular modeling combined with novel mathematical relationships integrating the thermodynamic/thermokinetic parameters of a series of isomeric multiconfigurations to predict the overall parameters in a range of pH values have been employed to study supramolecular dynamics at the molecular level. A suitable form of Eyring's equation was derived and a two-stage model was introduced. The new approach enabled accurate prediction of the apparent dissociation/association (koff/kon) and unbinding/binding (k-r/kr) rate constants of the ubiquitous multiconfiguration complexes of the supramolecular system. The pyronine Y (PY) was used as a model system for the validation of the presented method. Interestingly, the predicted koff value ((40 ± 1) × 10(5) s(-1), 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 ± 3) × 10(5) s(-1), 298 K). Moreover, the koff/kon and k-r/kr for flurbiprofen-β-cylcodextrin and ibuprofen-β-cyclodextrin systems were also predicted and suggested that the association processes are diffusion-controlled. The methodology is considered to be especially useful in the design and selection of excipients for a supramolecular system with preferred association and dissociation rate constants and understanding their mechanisms. It is believed that this new approach could be applicable to a wide range of ligand-receptor supramolecular systems and will surely help in understanding their complex mechanism. PMID:26840799

  1. Rate coefficients for dissociative attachment and resonant electron-impact dissociation involving vibrationally excited O{sub 2} molecules

    SciTech Connect

    Laporta, V.; Celiberto, R.; Tennyson, J.

    2014-12-09

    Rate coefficients for dissociative electron attachment and electron-impact dissociation processes, involving vibrationally excited molecular oxygen, are presented. Analytical fits of the calculated numerical data, useful in the applications, are also provided.

  2. Computational modeling toward understanding agonist binding on dopamine 3.

    PubMed

    Zhao, Yaxue; Lu, Xuefeng; Yang, Chao-Yie; Huang, Zhimin; Fu, Wei; Hou, Tingjun; Zhang, Jian

    2010-09-27

    The dopamine 3 (D3) receptor is a promising therapeutic target for the treatment of nervous system disorders, such as Parkinson's disease, and current research interests primarily focus on the discovery/design of potent D3 agonists. Herein, a well-designed computational protocol, which combines pharmacophore identification, homology modeling, molecular docking, and molecular dynamics (MD) simulations, was employed to understand the agonist binding on D3 aiming to provide insights into the development of novel potent D3 agonists. We (1) identified the chemical features required in effective D3 agonists by pharmacophore modeling based upon 18 known diverse D3 agonists; (2) constructed the three-dimensional (3D) structure of D3 based on homology modeling and the pharmacophore hypothesis; (3) identified the binding modes of the agonists to D3 by the correlation between the predicted binding free energies and the experimental values; and (4) investigated the induced fit of D3 upon agonist binding through MD simulations. The pharmacophore models of the D3 agonists and the 3D structure of D3 can be used for either ligand- or receptor-based drug design. Furthermore, the MD simulations further give the insight that the long and flexible EL2 acts as a "door" for agonist binding, and the "ionic lock" at the bottom of TM3 and TM6 is essential to transduce the activation signal. PMID:20695484

  3. Strategies for designing synthetic immune agonists.

    PubMed

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  4. Proglumide exhibits delta opioid agonist properties.

    PubMed

    Rezvani, A; Stokes, K B; Rhoads, D L; Way, E L

    1987-01-01

    Recently, it was reported that proglumide, a cholecystokinin (CCK) antagonist, potentiates the analgetic effects of morphine and endogenous opioid peptides and reverses morphine tolerance by antagonizing the CCK system in the central nervous system of the rat. In order to provide additional insight into the mode of action of this agent, we assessed the effect of proglumide in the isolated guinea pig ileum and the mouse, rat and rabbit vas deferens. Furthermore, we studied the in vitro binding affinity of this substance to mouse brain synaptosomes. Our results show that proglumide inhibits, dose dependently, the electrically stimulated twitches in the mouse vas deferens and guinea pig ileum, but not in the rat or rabbit vas deferens. The inhibitory action of proglumide on the mouse vas deferens, but not on the guinea pig ileum, is antagonized by naloxone and by the selective delta-antagonist, ICI 174,864, in a competitive fashion. Other CCK antagonists were found to be devoid of such activity on the mouse vas deferens. In vitro binding studies showed that proglumide displaces D-ala-D-[leucine]5-enkephalin (DADLE), a delta agonist, but not ethylketocyclazocine (EKC), a preferentially selective kappa agonist. The effect of proglumide appeared to be elicited presynaptically since it did not alter the norepinephrine-induced contractions of the mouse vas deferens. Our results suggest that proglumide might exert its opiate-like effects by activation of delta-opioid receptors. PMID:3030338

  5. Chimpanzees Extract Social Information from Agonistic Screams

    PubMed Central

    Slocombe, Katie E.; Kaller, Tanja; Call, Josep; Zuberbühler, Klaus

    2010-01-01

    Chimpanzee (Pan troglodytes) agonistic screams are graded vocal signals that are produced in a context-specific manner. Screams given by aggressors and victims can be discriminated based on their acoustic structure but the mechanisms of listener comprehension of these calls are currently unknown. In this study, we show that chimpanzees extract social information from these vocal signals that, combined with their more general social knowledge, enables them to understand the nature of out-of-sight social interactions. In playback experiments, we broadcast congruent and incongruent sequences of agonistic calls and monitored the response of bystanders. Congruent sequences were in accordance with existing social dominance relations; incongruent ones violated them. Subjects looked significantly longer at incongruent sequences, despite them being acoustically less salient (fewer call types from fewer individuals) than congruent ones. We concluded that chimpanzees categorised an apparently simple acoustic signal into victim and aggressor screams and used pragmatics to form inferences about third-party interactions they could not see. PMID:20644722

  6. Orientation-dependent dissociative charge transfer

    SciTech Connect

    Wu, W.; Prior, M.H.; Braeuning, H.

    1998-01-01

    Recoil-ion momentum spectroscopy and molecular fragment imaging techniques are combined to study dissociative electron capture from He by HeH{sup +} at 0.20-a.u. collision velocity. Groups of final HeH states which dissociate to ground or excited H and He atoms are separated. For each group, the experiment provides two-dimensional H fragment distributions with respect to the collision plane and for fixed transverse momentum transfer. These patterns show that the capture probability is highest for HeH{sup +} ions with their axis oriented normal to the scattering plane for two of the three groups populated. {copyright} {ital 1998} {ital The American Physical Society}

  7. Vibrational relaxation and dissociation in nitrogen

    NASA Technical Reports Server (NTRS)

    Varghese, Philip L.; Gonzales, David A.

    1991-01-01

    Calculations of the vibrational and dissociation transition probabilities are made for N2-N2 and N2-N collisions by means of a semiclassical N-state approximation. The flaws in previous techniques are reviewed, with special attention given to the prediction of overtones. The method presented ignores the effects of molecular rotation and employs a revised extended Rydberg intermolecular potential to describe diatom-diatom and diatom-atom collisions. The collision velocities investigated exhibit probabilities of less than unity by means of the N-state method. The continuum is quantized to treat dissociation, and the collision results demonstrate probability enhancements for V-V-T transitions in both bound-bound and bound-free transitions. The technique is of particular interest for the theoretical modeling of reentry flows such as those encountered in aerobraking maneuvers.

  8. The dissociation energy of N2

    NASA Technical Reports Server (NTRS)

    Almloef, Jan; Deleeuw, Bradley J.; Taylor, Peter R.; Bauschlicher, Charles W., Jr.; Siegbahn, Per

    1989-01-01

    The requirements for very accurate ab initio quantum chemical prediction of dissociation energies are examined using a detailed investigation of the nitrogen molecule. Although agreement with experiment to within 1 kcal/mol is not achieved even with the most elaborate multireference CI (configuration interaction) wave functions and largest basis sets currently feasible, it is possible to obtain agreement to within about 2 kcal/mol, or 1 percent of the dissociation energy. At this level it is necessary to account for core-valence correlation effects and to include up to h-type functions in the basis. The effect of i-type functions, the use of different reference configuration spaces, and basis set superposition error were also investigated. After discussing these results, the remaining sources of error in our best calculations are examined.

  9. Vibration dissociation coupling in nonequilibrium flows

    NASA Technical Reports Server (NTRS)

    Candler, Graham V.

    1992-01-01

    The final report on research between North Carolina State University and the NASA Ames Research Center is presented. The research was aimed at using the Schwartz, Slawsky, Herzfeld (SSH) theory to simulate the vibrational relaxation of nitrogen molecules undergoing dissociation or recombination over a wide range of conditions. The results of these simulations were then treated as exact, and they were used to develop a model for the coupled vibration-dissociation process. This new model is simple enough to be used in computational fluid dynamics codes, but still captures the physics of the complex process. The model is used to simulate the flow over typical geometries to test it and to determine how much impact it has on the flow field. The key elements of this research are summarized.

  10. Fluid hydrogen at high density - Pressure dissociation

    NASA Technical Reports Server (NTRS)

    Saumon, Didier; Chabrier, Gilles

    1991-01-01

    A model for the Helmholtz free energy of fluid hydrogen at high density and high temperature is developed. This model aims at describing both pressure and temperature dissociation and ionization and bears directly on equations of state of partially ionized plasmas, as encountered in astrophysical situations and high-pressure experiments. This paper focuses on a mixture of hydrogen atoms and molecules and is devoted to the study of the phenomenon of pressure dissociation at finite temperatures. In the present model, the strong interactions are described with realistic potentials and are computed with a modified Weeks-Chandler-Andersen fluid perturbation theory that reproduces Monte Carlo simulations to better than 3 percent. Theoretical Hugoniot curves derived from the model are in excellent agreement with experimental data.

  11. The charmonium dissociation in an ''anomalous wind''

    DOE PAGESBeta

    Sadofyev, Andrey V.; Yin, Yi

    2016-01-11

    We study the charmonium dissociation in a strongly coupled chiral plasma in the presence of magnetic field and axial charge imbalance. This type of plasma carries "anomalous flow" induced by the chiral anomaly and exhibits novel transport phenomena such as chiral magnetic effect. We found that the "anomalous flow" would modify the charmonium color screening length by using the gauge/gravity correspondence. We derive an analytical expression quantifying the "anomalous flow" experienced by a charmonium for a large class of chiral plasma with a gravity dual. We elaborate on the similarity and it qualitative difference between anomalous effects on the charmoniummore » color screening length which are model-dependent and those on the heavy quark drag force which are fixed by the second law of thermodynamics. As a result, we speculate on the possible charmonium dissociation induced by the chiral anomaly in heavy ion collisions.« less

  12. On the dissociation pathways of nitrobenzene

    NASA Astrophysics Data System (ADS)

    Kosmidis, C.; Ledingham, K. W. D.; Clark, A.; Marshall, A.; Jennings, R.; Sander, J.; Singhal, R. P.

    1994-08-01

    The fragmentation of nitrobenzene has been studied in the wavelength range 225-275 nm using a single dye laser, frequency doubled, in conjunction with a time-of-flight (TOF) mass spectrometer. The parent (C6H5NO2+), nitrosobenzene (C6H5NO+), phenoxy (C6H5O+) and phenyl (C6H5+) ions were all observed in addition to many other lighter daughter fragments. The formation of the nitrobenzene, phenoxy and phenyl ions are all explained invoking pathways where dissociation of the parent molecule from an excited state takes place first, followed by ionization after the absorption of further photons (DI) by the fragmented neutrals. Ionization of the parent molecule to states which are dissociative (ID) can explain the increase in the production of phenyl ions at wavelengths shorter than 230 nm.

  13. The charmonium dissociation in an "anomalous wind"

    NASA Astrophysics Data System (ADS)

    Sadofyev, Andrey V.; Yin, Yi

    2016-01-01

    We study the charmonium dissociation in a strongly coupled chiral plasma in the presence of magnetic field and axial charge imbalance. This type of plasma carries "anomalous flow" induced by the chiral anomaly and exhibits novel transport phenomena such as chiral magnetic effect. We found that the "anomalous flow" would modify the charmonium color screening length by using the gauge/gravity correspondence. We derive an analytical expression quantifying the "anomalous flow" experienced by a charmonium for a large class of chiral plasma with a gravity dual. We elaborate on the similarity and qualitative difference between anomalous effects on the charmonium color screening length which are model-dependent and those on the heavy quark drag force which are fixed by the second law of thermodynamics. We speculate on the possible charmonium dissociation induced by the chiral anomaly in heavy ion collisions.

  14. Theoretical dissociation energies for ionic molecules

    NASA Technical Reports Server (NTRS)

    Langhoff, S. R.; Bauschlicher, C. W., Jr.; Partridge, H.

    1986-01-01

    Ab initio calculations at the self-consistent-field and singles plus doubles configuration-interaction level are used to determine accurate spectroscopic parameters for most of the alkali and alkaline-earth fluorides, chlorides, oxides, sulfides, hydroxides, and isocyanides. Numerical Hartree-Fock (NHF) calculations are performed on selected systems to ensure that the extended Slater basis sets employed for the diatomic systems are near the Hartree-Fock limit. Extended Gaussian basis sets of at least triple-zeta plus double polarization equality are employed for the triatomic system. With this model, correlation effects are relatively small, but invariably increase the theoretical dissociation energies. The importance of correlating the electrons on both the anion and the metal is discussed. The theoretical dissociation energies are critically compared with the literature to rule out disparate experimental values. Theoretical (sup 2)Pi - (sup 2)Sigma (sup +) energy separations are presented for the alkali oxides and sulfides.

  15. Dynamics of Dissociative Electron Attachment to Methane

    NASA Astrophysics Data System (ADS)

    Rescigno, T. N.; Douguet, N.; Fonseca, S.; Orel, A. E.; Slaughter, D. S.; Belkacem, A.

    2015-05-01

    We present the results of a theoretical ad experimental study of dissociative electron attachment (DEA) to CH4. The total DEA cross section is dominated by a single broad peak centered near 10 eV, leading predominantly to H-/CH4 and CH2-/CH4dissociation channels. We will present evidence that both of these ion channels result from excitation of a triply degenerate Feshbach resonance (doubly excited negative ion state) of 2T2 symmetry whose parent is the lowest excited triplet state of the neutral molecule. We will present calculated angular distributions based on analysis of the entrance amplitudes obtained from the results of complex Kohn scattering calculations along with experimentally measured angular distributions obtained using the COLTRIMS method. Work performed under the auspices of the US DOE by the LBNL and supported by the U.S. DOE Office of Basic Energy Sciences, Division of Chemical Sciences.

  16. Dissociative Disorders: Between Neurosis and Psychosis

    PubMed Central

    Devillé, C.; Moeglin, C.; Sentissi, O.

    2014-01-01

    Dissociative disorders are a set of disorders defined by a disturbance affecting functions that are normally integrated with a prevalence of 2.4 percent in industrialised countries. These disorders are often poorly diagnosed or misdiagnosed because of sharing common clinical features with psychotic disorders, but requiring a very different trajectory of care. Repeated clinical situations in a crisis centre in Geneva provided us with a critical overview of current evidence of knowledge in clinical and etiopathological field about dissociative disorders. Because of their multiple expressions and the overlap with psychotic disorders, we focused on the clinical aspects using three different situations to better understand their specificity and to extend our thinking to the relevance of terms “neurosis” and “psychosis.” Finally, we hope that this work might help physicians and psychiatrists to become more aware of this complex set of disorders while making a diagnosis. PMID:25405051

  17. Dissociative Recombination Dynamics of the Ozone Cation

    SciTech Connect

    Zhaunerchyk, Vitali; Geppert, W.; sterdahl, F.; Larsson, Mats; Thomas, R. D.; Bahati Musafiri, Eric; Bannister, Mark E; Fogle, Mark R.; Vane, C Randy

    2008-02-01

    The dissociative recombination of the ozone cation has been studied at the heavy-ion storage ring CRYRING. The total cross section and branching fractions have been measured. The cross section from {approx}0eV to 0.2 eV follows a nearly E{sup -1} dependence, which was theoretically predicted to be a characteristic of the direct dissociative recombination mechanism. The thermal rate coefficient has been deduced from the cross section to be 7.37x10{sup -7}(T/300){sup -0.55}cm{sup 3}s{sup -1}. The branching fraction analysis carried out at {approx}0eV interaction energy has shown a strong propensity (94%) to dissociate through the three-body channel. Due to the overwhelming dominance of this channel it has been investigated in more detail. Of the six energetically available three-body pathways only three are significantly populated, such that the production of O(S1) is highly unfavored and all atomic oxygen fragments are predominantly formed in P3 and D1 states. Analysis of the breakup geometries has been performed by means of the Dalitz plot. It is observed that the molecules dissociating through the O(P3)+O(P3)+O(P3) and O(P3)+O(P3)+O(D1) channels have an open linear geometry where the cleavage of two valence bonds occurs preferentially in unison, while the O(P3)+O(D1)+O(D1) breakup might proceed partly through a sequential mechanism.

  18. Dynamics of dissociative electron attachment to ammonia

    NASA Astrophysics Data System (ADS)

    Rescigno, T. N.; Trevisan, C. S.; Orel, A. E.; Slaughter, D. S.; Adaniya, H.; Belkacem, A.; Weyland, Marvin; Dorn, Alexander; McCurdy, C. W.

    2016-05-01

    Ab initio theoretical studies and momentum-imaging experiments are combined to provide a consistent picture of the dynamics of dissociative electron attachment to ammonia through its 5.5- and 10.5-eV resonance channels. The present study clarifies the character and symmetry of the anion states involved and the dynamics that leads to the observed fragment-ion channels, their branching ratios, and angular distributions.

  19. The Bond Dissociation Energies of 1-Butene

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R. (Technical Monitor)

    1994-01-01

    The bond dissociation energies of 1-butene and several calibration systems are computed using the G2(MP2) approach. The agreement between the calibration systems and experiment is very good. The computed values for 1-butene are compared with calibration systems and the agreement between the computed results for 1-butene and the "rule of thumb" values from the smaller systems is remarkably good.

  20. Dissociative recombination of N2H+

    NASA Astrophysics Data System (ADS)

    dos Santos, S. Fonseca; Ngassam, V.; Orel, A. E.; Larson, Å.

    2016-08-01

    The direct and indirect mechanisms of dissociative recombination of N2H+ are theoretically studied. At low energies, the electron capture is found to be driven by recombination into bound Rydberg states, while at collision energies above 0.1 eV, the direct capture and dissociation along electronic resonant states becomes important. Electron-scattering calculations using the complex Kohn variational method are performed to obtain the scattering matrix as well as energy positions and autoionization widths of resonant states. Potential-energy surfaces of electronic bound states of N2H and N2H+ are computed using structure calculations with the multireference configuration interaction method. The cross section for the indirect mechanism is calculated using a vibrational frame transformation of the elements of the scattering matrix at energies just above the ionization threshold. Here vibrational excitations of the ionic core from v =0 to v =1 and v =2 for all three normal modes are considered and autoionization is neglected. The cross section for the direct dissociation along electronic resonant states is computed with wave-packet calculations using the multiconfiguration time-dependent Hartree method, where all three internal degrees of freedom are considered. The calculated cross sections are compared to measurements.

  1. Kinetics of single DNA hairpin dissociation

    NASA Astrophysics Data System (ADS)

    Rogers, William; Crocker, John

    2010-03-01

    Over the past decade, groups have used a variety of single molecule techniques to study the unfolding and unbinding of nucleic acids, proteins and other biomolecules. While some experiments on the dissociation of nucleic acids find exponential lifetime distributions, as expected for a process governed by a single rate-limiting pathway, other experiments find nonexponential lifetime distributions. In our work, we address this discrepancy by probing the force dependence of a single DNA hairpin under thermal dissociation. We use a scanning line optical tweezers instrument to measure the bound lifetimes of two DNA-coated microspheres under negligible applied tension. The two microspheres share a user-specified potential along the scan direction and are strongly confined in the perpendicular dimensions. The trapping laser intensity is modulated synchronously with a resonant scanning mirror to null all optical contributions to the pair interaction potential near contact. In addition, the laser polarization can be rotated to produce a continuously adjustable optical repulsion, allowing the instrument to double as a passive force clamp over a modest range of applied tensions. This unique experimental approach allows us to investigate many of the proposed explanations for nonexponential kinetics in nucleic acid dissociation that have, until now, been difficult to isolate.

  2. The infrared multiphoton dissociation of three nitrolkanes

    NASA Astrophysics Data System (ADS)

    Wodtke, A. M.; Hintsa, E. J.; Lee, Y. T.

    1986-01-01

    Infrared multiphoton dissociation in a molecular beam has been studied in order to elucidate the collision free, 'thermal' chemistry and dynamics of nitromethane, nitroethane and 2-nitropropane. The isomerization of CH3NO2 to CH3ONO was observed by detecting the CH3O and NO products from the dissociation of the very internally hot, isomerized nitromethane. A novel application of RRKM theory was used to estimate the barrier height to isomerization at 55.5 kcal/mol. The barrier height determination method was tested and found to give excellent results by applying it to the determintaion of the barrier height to HONO elimination from nitroethane, a value which is well known from activation energy measurements. The method was then applied to the case of HONO elimination from 2-nitropropane and it appears that there is good to believe that the barrier height is 3-5 kcal/mol lower in 2-nitropropane than in nitroethane. The success of this method for determining barrier heights shows how a microscopic molecular beam experiment, using infrared multiphoton dissociation where the concept of temperature has no place, can be quantitatively related to pyrolysis experiments which are conducted under collisional, thermal conditions and measure phenomenological quantities such as activation energies.

  3. Regional dissociated heterochrony in multivariate analysis.

    PubMed

    Mitteroecker, P; Gunz, P; Weber, G W; Bookstein, F L

    2004-12-01

    Heterochrony, the classic framework to study ontogeny and phylogeny, in essence relies on a univariate concept of shape. Though principal component plots of multivariate shape data seem to resemble classical bivariate allometric plots, the language of heterochrony cannot be translated directly into general multivariate methodology. We simulate idealized multivariate ontogenetic trajectories and demonstrate their behavior in principal component plots in shape space and in size-shape space. The concept of "dissociation", which is conventionally regarded as a change in the relationship between shape change and size change, appears to be algebraically the same as regional dissociation - the variation of apparent heterochrony by region. Only if the trajectories of two related species lie along exactly the same path in shape space can the classic terminology of heterochrony apply so that pure dissociation of size change against shape change can be detected. We demonstrate a geometric morphometric approach to these issues using adult and subadult crania of 48 Pan paniscus and 47 P. troglodytes. On each specimen we digitized 47 landmarks and 144 semilandmarks on ridge curves and the external neurocranial surface. The relation between these two species' growth trajectories is too complex for a simple summary in terms of global heterochrony. PMID:15646279

  4. Gas Hydrate Dissociation in the Ocean

    NASA Astrophysics Data System (ADS)

    Conroy, Devin; Smith, Stefan Llewellyn

    2006-11-01

    Methane gas is known to exist in extremely large quantities below the sea floor in the sediment of the deep and cold oceanic and in permafrost regions. Due to the large hydrostatic pressure and cool temperatures the gas reacts with the surrounding water to form a crystalline substance known as a gas hydrate. The fate of these reserves is very important to climate on earth because methane is a much more efficient greenhouse gas then carbon dioxide. The dissociation process in general can occur by either a decrease in pressure or an increase in temperature. In this study we concentrate on the latter. Once the hydrate dissociates, water and free gas remain above the phase boundary, occupying a larger volume than the original solid, and are be transported through the sediment. We have modeled this physical mechanism using volume averaged equations in a porous medium with a coupled two-phase flow. The movement of the phase boundary, which is proportional to the rate of heat transfer to this interface, is modeled as a Stefan type melting problem. The resultant governing equations are solved numerically, using a front fixing method to fix the phase boundary, to determine the rate of gas flux through the sediment and the dissociation rate.

  5. How thioredoxin dissociates its mixed disulfide.

    PubMed

    Roos, Goedele; Foloppe, Nicolas; Van Laer, Koen; Wyns, Lode; Nilsson, Lennart; Geerlings, Paul; Messens, Joris

    2009-08-01

    The dissociation mechanism of the thioredoxin (Trx) mixed disulfide complexes is unknown and has been debated for more than twenty years. Specifically, opposing arguments for the activation of the nucleophilic cysteine as a thiolate during the dissociation of the complex have been put forward. As a key model, the complex between Trx and its endogenous substrate, arsenate reductase (ArsC), was used. In this structure, a Cys29(Trx)-Cys89(ArsC) intermediate disulfide is formed by the nucleophilic attack of Cys29(Trx) on the exposed Cys82(ArsC)-Cys89(ArsC) in oxidized ArsC. With theoretical reactivity analysis, molecular dynamics simulations, and biochemical complex formation experiments with Cys-mutants, Trx mixed disulfide dissociation was studied. We observed that the conformational changes around the intermediate disulfide bring Cys32(Trx) in contact with Cys29(Trx). Cys32(Trx) is activated for its nucleophilic attack by hydrogen bonds, and Cys32(Trx) is found to be more reactive than Cys82(ArsC). Additionally, Cys32(Trx) directs its nucleophilic attack on the more susceptible Cys29(Trx) and not on Cys89(ArsC). This multidisciplinary approach provides fresh insights into a universal thiol/disulfide exchange reaction mechanism that results in reduced substrate and oxidized Trx. PMID:19675666

  6. Dissociative Disorders Among Chinese Inpatients Diagnosed With Schizophrenia

    PubMed Central

    Yu, Junhan; Ross, Colin A.; Keyes, Benjamin B.; Li, Ying; Dai, Yunfei; Zhang, Tianhong; Wang, Lanlan; Fan, Qing; Xiao, Zeping

    2010-01-01

    The purpose of the study was to assess the prevalence of dissociative disorders in a sample of Chinese psychiatric inpatients. Participants in the study consisted of 569 consecutively admitted inpatients at Shanghai Mental Health Center, China, of whom 84.9% had a clinical diagnosis of schizophrenia based on the Chinese Classification and Diagnostic Criteria for Mental Disorders, Version 3 (CCMD-3). All participants completed a self-report measure of dissociation, the Dissociative Experiences Scale (DES) and none had a prior diagnosis of a dissociative disorder. Ninety-six randomly selected participants were interviewed with a structured interview, the Dissociative Disorders Interview Schedule (DDIS) and a clinical interview. These 96 patients did not differ significantly from the 473 patients who were not interviewed on any demographic measures or on the self-report measure dissociation. A total of 28 (15.3%, after weighting of the data) patients received a clinical diagnosis of a dissociative disorder based on DSM-IV-TR criteria. Dissociative identity disorder was diagnosed in 2 (0.53%, after weighting) patients. Compared to the patients without a dissociative disorder, patients with dissociative disorders were significantly more likely to report childhood abuse (57.1% versus 22.1%), but the two groups did not differ significantly on any demographic measures. Dissociative disorders were readily identified in an inpatient psychiatric population in China. PMID:20603768

  7. Dissociation, PTSD, and substance abuse: an empirical study.

    PubMed

    Najavits, Lisa M; Walsh, Marybeth

    2012-01-01

    Few studies have examined the relationship between posttraumatic stress disorder (PTSD), substance use disorder, and dissociation. We studied 77 women with current PTSD and substance dependence, classified into high- versus low-dissociation groups per the Dissociative Experiences Scale. They were compared on trauma- and substance-related symptoms, cognitions, coping skills, social adjustment, trauma history, psychiatric symptoms, and self-harm/suicidal behaviors. We found the high-dissociation group consistently more impaired than the low-dissociation group. Also, the sample overall evidenced relatively high levels of dissociation, indicating that even in the presence of recent substance use, dissociation remains a major psychological phenomenon. Indeed, the high-dissociation group reported stronger expectation that substances could manage their psychiatric symptoms. The high-dissociation group also had more trauma-related symptoms and childhood histories of emotional abuse and physical neglect. The discussion addresses methodology, the "chemical dissociation" hypothesis, and the need for a more nuanced understanding of how substances are experienced in relation to dissociative phenomena. PMID:22211445

  8. Size-dependent dissociation of carbon monoxide on cobalt nanoparticles.

    PubMed

    Tuxen, Anders; Carenco, Sophie; Chintapalli, Mahati; Chuang, Cheng-Hao; Escudero, Carlos; Pach, Elzbieta; Jiang, Peng; Borondics, Ferenc; Beberwyck, Brandon; Alivisatos, A Paul; Thornton, Geoff; Pong, Way-Faung; Guo, Jinghua; Perez, Ruben; Besenbacher, Flemming; Salmeron, Miquel

    2013-02-13

    In situ soft X-ray absorption spectroscopy (XAS) was employed to study the adsorption and dissociation of carbon monoxide molecules on cobalt nanoparticles with sizes ranging from 4 to 15 nm. The majority of CO molecules adsorb molecularly on the surface of the nanoparticles, but some undergo dissociative adsorption, leading to oxide species on the surface of the nanoparticles. We found that the tendency of CO to undergo dissociation depends critically on the size of the Co nanoparticles. Indeed, CO molecules dissociate much more efficiently on the larger nanoparticles (15 nm) than on the smaller particles (4 nm). We further observed a strong increase in the dissociation rate of adsorbed CO upon exposure to hydrogen, clearly demonstrating that the CO dissociation on cobalt nanoparticles is assisted by hydrogen. Our results suggest that the ability of cobalt nanoparticles to dissociate hydrogen is the main parameter determining the reactivity of cobalt nanoparticles in Fischer-Tropsch synthesis. PMID:23339635

  9. Development, reliability, and validity of a child dissociation scale.

    PubMed

    Putnam, F W; Helmers, K; Trickett, P K

    1993-01-01

    Dissociation is a complex psychophysiological process that ranges along a continuum from minor, normal dissociation to Axis I psychopathology. High levels of dissociation are associated with increased self-destructive behaviors and other symptoms. Although several validated measures of dissociation exist for adults, no measures are available for children. The Child Dissociative Checklist (CDC) was developed to meet this need and is a reliable and valid observer report measure of dissociation in children. The CDC had a 1-year test-retest reliability coefficient of rho = .69 (N = 73, p = .0001) in a sample of normal and sexually abused girls. The CDC had high discriminant validity among four test samples including: normal control girls, sexually abused girls, boys and girls with dissociative disorder NOS and boys and girls with multiple personality disorder. The CDC is intended as a clinical screening instrument and as a research measure. The CDC is not designed to be used as a diagnostic instrument. PMID:8287286

  10. Exploring the relationships between dissociation, victimization, and juvenile sexual offending.

    PubMed

    Leibowitz, George S; Laser, Julie A; Burton, David L

    2011-01-01

    An etiological model of sexually abusive behavior including dissociation could have utility for researchers and treatment providers working with sexually abusive youth with trauma histories. This article explores relationships between dissociation, victimization, and juvenile sexual offending. Self-reported data on dissociation and 5 types of abuse were collected from 2 racially/ethnically diverse groups of sexually abusive and general delinquent male adolescents (n = 502). Bivariate analysis showed significant correlations between all types of child abuse and dissociation with the exception of emotional neglect. Hierarchical logistic regression analysis indicated that dissociation was significant in predicting sexual offender status. Moreover, dissociation, sexual victimization, and physical abuse showed significant effects in predicting membership in the sexual offender group. The results confirm the need for additional research in the areas of assessment and treatment of dissociation among sexually abusive youth. PMID:21240737

  11. Self-assembling peptide for co-delivery of HIV-1 CD8+ T cells epitope and Toll-like receptor 7/8 agonists R848 to induce maturation of monocyte derived dendritic cell and augment polyfunctional cytotoxic T lymphocyte (CTL) response.

    PubMed

    Ding, Yong; Liu, Jun; Lu, Sheng; Igweze, Justice; Xu, Wen; Kuang, Da; Zealey, Chris; Liu, Daheng; Gregor, Alex; Bozorgzad, Ardalan; Zhang, Lei; Yue, Elizabeth; Mujib, Shariq; Ostrowski, Mario; Chen, P

    2016-08-28

    Peptide based vaccine that incorporates one or several highly conserved CD8+ T cells epitopes to induce potent cytotoxic T lymphocyte (CTL) response is desirable for some infectious diseases, such as HIV-1 (human immunodeficiency virus-1), and cancers. However, the CD8+ T cells epitope is often weakly immunogenic, and thus requires a specific adjuvant or delivery system to enhance the efficiency. Here we investigated the use of self-assembling peptide EAK16-II based platform to achieve the co-delivery of CD8+ T cells epitope and TLR7/8 agonists (R848 or R837) for augmenting DCs maturation and HIV-1 specific CTL response. HIV-1 CTL epitope SL9 was conjugated with EAK16-II to obtain SL9-EAK16-II, which further spontaneously co-assembled with R848 or R837 in aqueous solution, forming co-assembled nanofibers. Fluorescence spectra and calorimetrical titration revealed the interaction between SL9-EAK16-II assemblies and R848 or R837 via hydrogen bonding and hydrophobic interaction, with the binding affinity (dissociation constant Kd) of 0.62μM or 0.53μM, respectively. Ex vivo generated DCs from HIV-1+ patients pulsed with the SL9-EAK16-II/R848 nanofibers stimulated significantly more polyfunctional SL9 specific CTLs, compared to the DCs pulsed with SL9 alone or the mixture of SL9 and TLR agonist. Furthermore, the nanofibers elicited stronger SL9 specific CTL response in vaccinated mice. Our findings suggest the self-assembling peptide EAK16-II might be used as a new delivery system for peptide based vaccines. PMID:27297778

  12. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.

    PubMed

    Hussy, N; Deleuze, C; Pantaloni, A; Desarménien, M G; Moos, F

    1997-08-01

    1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30

  13. Ab initio calculations of dissociative attachment and dissociative recombination of electrons and polyatomic species

    NASA Astrophysics Data System (ADS)

    Haxton, Daniel

    2009-05-01

    Interactions of free electrons with neutral and positively charged molecular species play a role in various physical systems. In interstellar space, reactions such as dissociative recombination determine the balance of various charged and neutral species. In a laboratory equipped with an apparatus like a COLTRIMS device, the dissociative attachment process can be used as a microscope to study polyatomic molecular dynamics. We discuss the theoretical and numerical methods used to calculate dissociative attachment and dissociative recombination of electrons with larger molecules from first principles. Studies using these methods are complimentary to other methods that yield more approximate reaction rates at greatly lesser numerical cost; they may yield precise information about the dissociation dynamics, product distribution, and differential cross section that approximate methods cannot. We discuss calculations performed to date on the target species H2O, NO2, and LiH2^+. We discuss the scaling of our numerical methods with the number of atoms, and the prospects of applying them to tetra-atomics.

  14. Constant Communities in Complex Networks

    NASA Astrophysics Data System (ADS)

    Chakraborty, Tanmoy; Srinivasan, Sriram; Ganguly, Niloy; Bhowmick, Sanjukta; Mukherjee, Animesh

    2013-05-01

    Identifying community structure is a fundamental problem in network analysis. Most community detection algorithms are based on optimizing a combinatorial parameter, for example modularity. This optimization is generally NP-hard, thus merely changing the vertex order can alter their assignments to the community. However, there has been less study on how vertex ordering influences the results of the community detection algorithms. Here we identify and study the properties of invariant groups of vertices (constant communities) whose assignment to communities are, quite remarkably, not affected by vertex ordering. The percentage of constant communities can vary across different applications and based on empirical results we propose metrics to evaluate these communities. Using constant communities as a pre-processing step, one can significantly reduce the variation of the results. Finally, we present a case study on phoneme network and illustrate that constant communities, quite strikingly, form the core functional units of the larger communities.

  15. Design, synthesis, pharmacological characterization of a fluorescent agonist of the P2Y₁₄ receptor.

    PubMed

    Kiselev, Evgeny; Balasubramanian, Ramachandran; Uliassi, Elisa; Brown, Kyle A; Trujillo, Kevin; Katritch, Vsevolod; Hammes, Eva; Stevens, Raymond C; Harden, T Kendall; Jacobson, Kenneth A

    2015-11-01

    The P2Y14R is a G(i/o)-coupled receptor of the P2Y family of purinergic receptors that is activated by extracellular UDP and UDP-glucose (UDPG). In an earlier report we described a P2Y14R fluorescent probe, MRS4174, based on the potent and selective antagonist PPTN, a naphthoic acid derivative. Here, we report the design, preparation, and activity of an agonist-based fluorescent probe MRS4183 (11) and a shorter P2Y14R agonist congener, which contain a UDP-glucuronic acid pharmacophore and BODIPY fluorophores conjugated through diaminoalkyl linkers. The design relied on both docking in a P2Y14R homology model and established structure activity relationship (SAR) of nucleotide analogs. 11 retained P2Y14R potency with EC50 value of 0.96 nM (inhibition of adenylyl cyclase), compared to parent UDPG (EC50 47 nM) and served as a tracer for microscopy and flow cytometry, displaying minimal nonspecific binding. Binding saturation analysis gave an apparent binding constant for 11 in whole cells of 21.4±1.1 nM, with a t1/2 of association at 50 nM 11 of 23.9 min. Known P2Y14R agonists and PPTN inhibited cell binding of 11 with the expected rank order of potency. The success in the identification of a new P2Y14R fluorescent agonist with low nonspecific binding illustrates the advantages of rational design based on recently determined GPCR X-ray structures. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. PMID:26303895

  16. Dissociative depression among women with fibromyalgia or rheumatoid arthritis.

    PubMed

    Kilic, Ozge; Sar, Vedat; Taycan, Okan; Aksoy-Poyraz, Cana; Erol, Turgut C; Tecer, Ozlem; Emul, Murat H; Ozmen, Mine

    2014-01-01

    The aim of this study was to inquire about the possible relations of childhood trauma, anger, and dissociation to depression among women with fibromyalgia or rheumatoid arthritis. Fifty female patients diagnosed as having fibromyalgia (n = 30) or rheumatoid arthritis (n = 20) participated in the study. The Childhood Trauma Questionnaire, Somatoform Dissociation Questionnaire (SDQ), Dissociation Questionnaire (DIS-Q), Beck Depression Inventory (BDI), Spielberger State-Trait Anger Expression Inventory, and Dissociative Disorders Interview Schedule were administered to all participants. Women with a lifetime diagnosis of depressive disorder had higher scores for somatoform and psychoform dissociation than the nondepressive patients. However, childhood trauma scores did not differ between the 2 groups. In regression analysis, current severity of depression (BDI) was predicted by psychoform dissociation (DIS-Q) and lower education, and lifetime diagnosis of major depression was predicted by somatoform dissociation (SDQ). Whereas childhood emotional neglect predicted somatoform dissociation, psychoform dissociation was predicted by childhood sexual abuse. Mental processing of anger seems to be 1 of the dimensions of psychodynamics in trauma-related depressive conditions. In the context of the perceived threat of loss of control due to expressed anger and mental disintegration, somatoform dissociation seems to contribute to overmodulation of emotions in dissociative depression. Among patients suffering from physical illness with possible psychosomatic dimensions, assessment of somatoform dissociation in addition to psychoform dissociation may be helpful to understand diverse psychopathological trajectories emerging in the aftermath of childhood adversities. The recently proposed category of "dissociative depression" (Sar, 2011) seems to be a promising concept for future research on psychosomatic aspects of traumatic stress. PMID:24228798

  17. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  18. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  19. Dissociative diffusion mechanism in vacancy-rich materials according to mass action kinetics

    NASA Astrophysics Data System (ADS)

    Biderman, N. J.; Sundaramoorthy, R.; Haldar, Pradeep; Lloyd, J. R.

    2016-05-01

    Two sets of diffusion-reaction numerical simulations using a finite difference method (FDM) were conducted to investigate fast impurity diffusion via interstitial sites in vacancy-rich materials such as Cu(In,Ga)Se2 (CIGS) and Cu2ZnSn(S, Se)4 (CZTSSe or CZTS) via the dissociative diffusion mechanism where the interstitial diffuser ultimately reacts with a vacancy to produce a substitutional. The first set of simulations extends the standard interstitial-limited dissociative diffusion theory to vacancy-rich material conditions where vacancies are annihilated in large amounts, introducing non-equilibrium vacancy concentration profiles. The second simulation set explores the vacancy-limited dissociative diffusion where impurity incorporation increases the equilibrium vacancy concentration. In addition to diffusion profiles of varying concentrations and shapes that were obtained in all simulations, some of the profiles can be fitted with the constant- and limited-source solutions of Fick's second law despite the non-equilibrium condition induced by the interstitial-vacancy reaction. The first set of simulations reveals that the dissociative diffusion coefficient in vacancy-rich materials is inversely proportional to the initial vacancy concentration. In the second set of numerical simulations, impurity-induced changes in the vacancy concentration lead to distinctive diffusion profile shapes. The simulation results are also compared with published data of impurity diffusion in CIGS. According to the characteristic properties of diffusion profiles from the two set of simulations, experimental detection of the dissociative diffusion mechanism in vacancy-rich materials may be possible.

  20. Multiphoton dissociation and thermal unimolecular reactions induced by infrared lasers. [REAMPA code

    SciTech Connect

    Dai, H.L.

    1981-04-01

    Multiphoton dissociation (MPD) of ethyl chloride was studied using a tunable 3.3 ..mu..m laser to excite CH stretches. The absorbed energy increases almost linearly with fluence, while for 10 ..mu..m excitation there is substantial saturation. Much higher dissociation yields were observed for 3.3 ..mu..m excitation than for 10 ..mu..m excitation, reflecting bottlenecking in the discrete region of 10 ..mu..m excitation. The resonant nature of the excitation allows the rate equations description for transitions in the quasicontinuum and continuum to be extended to the discrete levels. Absorption cross sections are estimated from ordinary ir spectra. A set of cross sections which is constant or slowly decreasing with increasing vibrational excitation gives good fits to both absorption and dissociation yield data. The rate equations model was also used to quantitatively calculate the pressure dependence of the MPD yield of SF/sub 6/ caused by vibrational self-quenching. Between 1000-3000 cm/sup -1/ of energy is removed from SF/sub 6/ excited to approx. > 60 kcal/mole by collision with a cold SF/sub 6/ molecule at gas kinetic rate. Calculation showed the fluence dependence of dissociation varies strongly with the gas pressure. Infrared multiphoton excitation was applied to study thermal unimolecular reactions. With SiF/sub 4/ as absorbing gas for the CO/sub 2/ laser pulse, transient high temperature pulses were generated in a gas mixture. IR fluorescence from the medium reflected the decay of the temperature. The activation energy and the preexponential factor of the reactant dissociation were obtained from a phenomenological model calculation. Results are presented in detail. (WHK)

  1. Dissociative symptoms and dissociative disorders comorbidity in obsessive compulsive disorder: Symptom screening, diagnostic tools and reflections on treatment.

    PubMed

    Belli, Hasan

    2014-08-16

    Borderline personality disorder, conversion disorder and obsessive compulsive disorder frequently have dissociative symptoms. The literature has demonstrated that the level of dissociation might be correlated with the severity of obsessive compulsive disorder (OCD) and that those not responding to treatment had high dissociative symptoms. The structured clinical interview for DSM-IV dissociative disorders, dissociation questionnaire, somatoform dissociation questionnaire and dissociative experiences scale can be used for screening dissociative symptoms and detecting dissociative disorders in patients with OCD. However, a history of neglect and abuse during childhood is linked to a risk factor in the pathogenesis of dissociative psychopathology in adults. The childhood trauma questionnaire-53 and childhood trauma questionnaire-40 can be used for this purpose. Clinicians should not fail to notice the hidden dissociative symptoms and childhood traumatic experiences in OCD cases with severe symptoms that are resistant to treatment. Symptom screening and diagnostic tools used for this purpose should be known. Knowing how to treat these pathologies in patients who are diagnosed with OCD can be crucial. PMID:25133142

  2. Estrogen receptor beta agonists in neurobehavioral investigations.

    PubMed

    Choleris, Elena; Clipperton, Amy E; Phan, Anna; Kavaliers, Martin

    2008-07-01

    Neurobehavioral investigations into the functions of estrogen receptor (ER)alpha and ERbeta have utilized 'knockout' mice, phytoestrogens and, more recently, ER-specific agonists. Feeding, sexual, aggressive and social behavior, anxiety, depression, drug abuse, pain perception, and learning (and associated synaptic plasticity) are affected by ERalpha and ERbeta in a manner that is dependent upon the specific behavior studied, gender and developmental stage. Overall, ERalpha and ERbeta appear to function together to foster sociosexual behavior while inhibiting behaviors that, if occurring at the time of behavioral estrous, may compete with reproduction (eg, feeding). Recently developed pharmacological tools have limited selectivity and availability to the research community at large, as they are not commercially available. The development of highly selective, commercially available ERbeta-specific antagonists would greatly benefit preclinical and applied research. PMID:18600582

  3. Non-Benzodiazepine Receptor Agonists for Insomnia.

    PubMed

    Becker, Philip M; Somiah, Manya

    2015-03-01

    Because of proven efficacy, reduced side effects, and less concern about addiction, non-benzodiazepine receptor agonists (non-BzRA) have become the most commonly prescribed hypnotic agents to treat onset and maintenance insomnia. First-line treatment is cognitive-behavioral therapy. When pharmacologic treatment is indicated, non-BzRA are first-line agents for the short-term and long-term management of transient and chronic insomnia related to adjustment, psychophysiologic, primary, and secondary causation. In this article, the benefits and risks of non-BzRA are reviewed, and the selection of a hypnotic agent is defined, based on efficacy, pharmacologic profile, and adverse events. PMID:26055674

  4. Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl.

    PubMed

    Maguire, David R; France, Charles P

    2016-08-01

    Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ(9)-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse. The degree to which cannabinoids enhance antinociceptive effects of opioids varies across drugs insofar as Δ(9)-THC and the synthetic cannabinoid receptor agonist CP55940 increase the potency of some mu opioid receptor agonists (e.g., fentanyl) more than others (e.g., nalbuphine). It is not known whether interactions between cannabinoids and opioids vary similarly for other (abuse-related) effects. This study examined whether Δ(9)-THC and CP55940 differentially impact the discriminative stimulus effects of fentanyl and nalbuphine in monkeys (n=4) discriminating 0.01mg/kg of fentanyl (s.c.) from saline. Fentanyl (0.00178-0.0178mg/kg) and nalbuphine (0.01-0.32mg/kg) dose-dependently increased drug-lever responding. Neither Δ(9)-THC (0.032-1.0mg/kg) nor CP55940 (0.0032-0.032mg/kg) enhanced the discriminative stimulus effects of fentanyl or nalbuphine; however, doses of Δ(9)-THC and CP55940 that shifted the nalbuphine dose-effect curve markedly to the right and/or down were less effective or ineffective in shifting the fentanyl dose-effect curve. The mu opioid receptor antagonist naltrexone (0.032mg/kg) attenuated the discriminative stimulus effects of fentanyl and nalbuphine similarly. These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability. PMID:27184925

  5. Effective cosmological constant induced by stochastic fluctuations of Newton's constant

    NASA Astrophysics Data System (ADS)

    de Cesare, Marco; Lizzi, Fedele; Sakellariadou, Mairi

    2016-09-01

    We consider implications of the microscopic dynamics of spacetime for the evolution of cosmological models. We argue that quantum geometry effects may lead to stochastic fluctuations of the gravitational constant, which is thus considered as a macroscopic effective dynamical quantity. Consistency with Riemannian geometry entails the presence of a time-dependent dark energy term in the modified field equations, which can be expressed in terms of the dynamical gravitational constant. We suggest that the late-time accelerated expansion of the Universe may be ascribed to quantum fluctuations in the geometry of spacetime rather than the vacuum energy from the matter sector.

  6. Stability evaluation of hydrate-bearing sediments during thermally-driven hydrate dissociation

    NASA Astrophysics Data System (ADS)

    Kwon, T.; Cho, G.; Santamarina, J.; Kim, H.; Lee, J.

    2009-12-01

    Hydrate-bearing sediments may destabilize spontaneously as part of geological processes, unavoidably during petroleum drilling/production operations, or intentionally as part of gas extraction from the hydrate itself. In all cases, high pore fluid pressure generation is anticipated during hydrate dissociation. This study examined how thermal changes destabilize gas hydrate-bearing sediments. First, an analytical formulation was derived for predicting fluid pressure evolution in hydrate-bearing sediments subjected to thermal stimulation without mass transfer. The formulation captures the self-preservation behavior, calculates the hydrate and free gas quantities during dissociation, considering effective stress-controlled sediment compressibility and gas solubility in aqueous phase. Pore fluid pressure generation is proportional to the initial hydrate fraction and the sediment bulk stiffness; is inversely proportional to the initial gas fraction and gas solubility; and is limited by changes in effective stress that cause the failure of the sediment. Second, the analytical formulation for hydrate dissociation was incorporated as a user-defined function into a verified finite difference code (FLAC2D). The underlying physical processes of hydrate-bearing sediments, including hydrate dissociation, self-preservation, pore pressure evolution, gas dissolution, and sediment volume expansion, were coupled with the thermal conduction, pore fluid flow, and mechanical response of sediments. We conducted the simulations for a duration of 20 years, assuming a constant-temperature wellbore transferred heat to the surrounding hydrate-bearing sediments, resulting in dissociation of methane hydrate in the well vicinity. The model predicted dissociation-induced excess pore fluid pressures which resulted in a large volume expansion and plastic deformation of the sediments. Furthermore, when the critical stress was reached, localized shear failure of the sediment around the borehole was

  7. Dissociation, PTSD, and Substance Abuse: An Empirical Study

    PubMed Central

    Najavits, Lisa; Walsh, Marybeth

    2012-01-01

    Few studies have examined the relationship between posttraumatic stress disorder (PTSD), substance use disorder (SUD) and dissociation. We studied 77 women with current PTSD and substance dependence, classified into high- versus low-dissociation on the Dissociative Experiences Scale. They were compared on trauma- and substance-related symptoms, cognitions, coping skills, social adjustment, trauma history, psychiatric symptoms, and self-harm/suicidal behaviors. We found the high-dissociation group consistently more impaired than the low-dissociation group. Also, the sample overall evidenced relatively high levels of dissociation, indicating that even in the presence of recent substance use, dissociation remains a major psychological phenomenon. Indeed, the high-dissociation group reported stronger expectation that substances could manage their psychiatric symptoms. The high-dissociation group also had more trauma-related symptoms and childhood histories of emotional abuse and physical neglect. Discussion addresses methodology, the “chemical dissociation” hypothesis, and the need for more nuanced understanding of how substances are experienced in relation to dissociative phenomena. PMID:22211445

  8. The role of water in gas hydrate dissociation

    USGS Publications Warehouse

    Circone, S.; Stern, L.A.; Kirby, S.H.

    2004-01-01

    When raised to temperatures above the ice melting point, gas hydrates release their gas in well-defined, reproducible events that occur within self-maintained temperature ranges slightly below the ice point. This behavior is observed for structure I (carbon dioxide, methane) and structure II gas hydrates (methane-ethane, and propane), including those formed with either H2O- or D2O-host frameworks, and dissociated at either ambient or elevated pressure conditions. We hypothesize that at temperatures above the H2O (or D2O) melting point: (1) hydrate dissociation produces water + gas instead of ice + gas, (2) the endothermic dissociation reaction lowers the temperature of the sample, causing the water product to freeze, (3) this phase transition buffers the sample temperatures within a narrow temperature range just below the ice point until dissociation goes to completion, and (4) the temperature depression below the pure ice melting point correlates with the average rate of dissociation and arises from solution of the hydrate-forming gas, released by dissociation, in the water phase at elevated concentrations. In addition, for hydrate that is partially dissociated to ice + gas at lower temperatures and then heated to temperatures above the ice point, all remaining hydrate dissociates to gas + liquid water as existing barriers to dissociation disappear. The enhanced dissociation rates at warmer temperatures are probably associated with faster gas transport pathways arising from the formation of water product.

  9. Optical constants of solid methane

    NASA Technical Reports Server (NTRS)

    Khare, Bishun N.; Thompson, W. R.; Sagan, C.; Arakawa, E. T.; Bruel, C.; Judish, J. P.; Khanna, R. K.; Pollack, J. B.

    1989-01-01

    Methane is the most abundant simple organic molecule in the outer solar system bodies. In addition to being a gaseous constituent of the atmospheres of the Jovian planets and Titan, it is present in the solid form as a constituent of icy surfaces such as those of Triton and Pluto, and as cloud condensate in the atmospheres of Titan, Uranus, and Neptune. It is expected in the liquid form as a constituent of the ocean of Titan. Cometary ices also contain solid methane. The optical constants for both solid and liquid phases of CH4 for a wide temperature range are needed for radiative transfer calculations, for studies of reflection from surfaces, and for modeling of emission in the far infrared and microwave regions. The astronomically important visual to near infrared measurements of solid methane optical constants are conspicuously absent from the literature. Preliminary results are presented of the optical constants of solid methane for the 0.4 to 2.6 micron region. K is reported for both the amorphous and the crystalline (annealed) states. Using the previously measured values of the real part of the refractive index, n, of liquid methane at 110 K n is computed for solid methane using the Lorentz-Lorentz relationship. Work is in progress to extend the measurements of optical constants n and k for liquid and solid to both shorter and longer wavelengths, eventually providing a complete optical constants database for condensed CH4.

  10. How fundamental are fundamental constants?

    NASA Astrophysics Data System (ADS)

    Duff, M. J.

    2015-01-01

    I argue that the laws of physics should be independent of one's choice of units or measuring apparatus. This is the case if they are framed in terms of dimensionless numbers such as the fine structure constant, ?. For example, the standard model of particle physics has 19 such dimensionless parameters whose values all observers can agree on, irrespective of what clock, rulers or scales? they use to measure them. Dimensional constants, on the other hand, such as ?, c, G, e and k ?, are merely human constructs whose number and values differ from one choice of units to the next. In this sense, only dimensionless constants are 'fundamental'. Similarly, the possible time variation of dimensionless fundamental 'constants' of nature is operationally well defined and a legitimate subject of physical enquiry. By contrast, the time variation of dimensional constants such as ? or ? on which a good many (in my opinion, confusing) papers have been written, is a unit-dependent phenomenon on which different observers might disagree depending on their apparatus. All these confusions disappear if one asks only unit-independent questions. We provide a selection of opposing opinions in the literature and respond accordingly.

  11. In vivo (/sup 3/H)spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    SciTech Connect

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-06-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist (3H)spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo (3H)spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of (3H)spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound (3H)spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to (3H)spiperone injection resulted in a selective increase of in vivo (3H)spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.

  12. Imagination and dissociation in hypnotic responding.

    PubMed

    Bowers, K S

    1992-10-01

    A neodissociative model of mind is better equipped than a social-psychological model to deal with the complexities of hypnosis, and of human behavior generally. It recognizes, as Coe's (1992) model does not, that behavior can be more automatically activated than strategically enacted. In particular, Coe's emphasis on human behavior as purposeful and goal directed does not distinguish between goal-directed behavior that serves a purpose, and goal-directed behavior that is performed on purpose. It is this distinction that permits goal-directed behavior to be dissociated from a person's conscious plans and intentions. In addition to offering a critique of Coe's "limited process" view of hypnosis, 4 main points are made in the interest of developing a slightly modified, neodissociation view of hypnosis. First, it is argued that goal-directed fantasies are more limited in their ability to mediate hypnotic responding than is commonly appreciated; as well, they do not seem to account for the nonvolitional quality of hypnotic responding. Second, it is argued that hypnotic ability is not unidimensional, with compliance and social influence more apt to account for the low than for the high hypnotizable's responsiveness to suggestion. Third, compared to low hypnotizables, the hypnotic responsiveness of high hypnotizables seems more likely to result from dissociated control. In other words, for high hypnotizables, hypnotic suggestions may often directly activate subsystems of cognitive control. Consequently, the need for executive initiative and effort to produce hypnotically suggested behavior is minimized, and such responses are therefore experienced as nonvolitional. Fourth and finally, while goal-directed fantasies typically accompany hypnotically suggested responses, they are in many cases more a marker of dissociated control than a mediator of suggested effects. PMID:1468834

  13. Occipitocervical dissociation-incidence, evaluation, and treatment.

    PubMed

    Kasliwal, Manish K; Fontes, Ricardo B; Traynelis, Vincent C

    2016-09-01

    Traumatic occipitocervical dissociation (OCD) results from ligamentous injury to the craniocervical junction and is associated with a high rate of mortality and significant neurologic morbidity. The diagnosis is frequently missed on initial lateral cervical spinal radiographs mainly due to inadequate visualization of radiological landmarks and low degree of suspicion. Widespread availability of multidetector computed tomography (MDCT) of the spine and development of better diagnostic radiological criteria has allowed timely diagnosis and good clinical outcome following posterior occipitocervical fusion and instrumentation for a pathology that was once considered uniformly fatal. The present paper reviews the clinical features, diagnosis, and management of OCD in light of most recent literature. PMID:27255101

  14. On the dissociation energy of Mg2

    NASA Technical Reports Server (NTRS)

    Partridge, Harry; Bauschlicher, Charles W., Jr.; Pettersson, Lars G. M.; Mclean, A. D.; Liu, Bowen

    1990-01-01

    The bonding in the X 1Sigma(+)g state of Mg2 is investigated using near-complete valence one-particle Slater and Gaussian basis sets containing up to h functions. It is shown that the four-electron complete CI limit can be approached using a sequence of either second-order CI (SOCI) or interacting correlated fragment (ICF) calculations. At the valence level, the best estimate of the dissociation energy D(e) was 464/cm. This is a lower limit and is probably within 5/cm of the complete basis value.

  15. Spin–orbit interaction mediated molecular dissociation

    SciTech Connect

    Kokkonen, E. Jänkälä, K.; Kettunen, J. A.; Heinäsmäki, S.; Karpenko, A.; Huttula, M.; Löytynoja, T.

    2014-05-14

    The effect of the spin–orbit interaction to photofragmentation is investigated in the mercury(II) bromide (HgBr{sub 2}) molecule. Changes in the fragmentation between the two spin–orbit components of Hg 5d photoionization, as well as within the molecular-field-splitted levels of these components are observed. Dissociation subsequent to photoionization is studied with synchrotron radiation and photoelectron-photoion coincidence spectroscopy. The experimental results are accompanied by relativistic ab initio analysis of the photoelectron spectrum.

  16. Dissociative Ionization of Aromatic and Heterocyclic Molecules

    NASA Technical Reports Server (NTRS)

    Huo, Winifred M.

    2003-01-01

    Space radiation poses a major health hazard to humans in space flight. The high-energy charged particles in space radiation ranging from protons to high atomic number, high-energy (HZE) particles, and the secondary species they produce, attack DNA, cells, and tissues. Of the potential hazards, long-term health effects such as carcinogenesis are likely linked to the DNA lesions caused by secondary electrons in the 1 - 30 eV range. Dissociative ionization (DI) is one of the electron collision processes that can damage the DNA, either directly by causing a DNA lesion, or indirectly by producing radicals and cations that attack the DNA. To understand this process, we have developed a theoretical model for DI. Our model makes use of the fact that electron motion is much faster than nuclear motion and assumes DI proceeds through a two-step process. The first step is electron-impact ionization resulting in a particular state of the molecular ion in the geometry of the neutral molecule. In the second step the ion undergoes unimolecular dissociation. Thus the DI cross section sigma(sup DI)(sub a) for channel a is given by sigma(sup DI)(sub a) = sigma(sup I)(sub a) P(sub D) with sigma(sup I)(sub a) the ionization cross section of channel a and P(sub D) the dissociation probability. This model has been applied to study the DI of H2O, NH3, and CH4, with results in good agreement with experiment. The ionization cross section sigma(sup I)(sub a) was calculated using the improved binary encounter-dipole model and the unimolecular dissociation probability P(sub D) obtained by following the minimum energy path determined by the gradients and Hessians of the electronic energy with respect to the nuclear coordinates of the ion. This model is used to study the DI from the low-lying channels of benzene and pyridine to understand the different product formation in aromatic and heterocyclic molecules. DI study of the DNA base thymine is underway. Solvent effects will also be discussed.

  17. Towards an accurate dissociative potential for water

    NASA Astrophysics Data System (ADS)

    Akin-Ojo, Omololu

    2014-03-01

    Most models of water describe the molecule as rigid, i.e., with fixed bond angles and bond lengths, or as flexible in which the bond angles and bond lengths vary but the chemical bonds cannot be broken. In this work we present our progress in the development of a water model which allows for the breaking and formation of chemical bonds. The force field was obtained by fitting ab initio (not DFT) energies, forces, and molecular properties. The ability of the model to predict properties of water at ambient and extreme conditions will be presented. We will also report on the modeling of small clusters of water using the dissociative force field.

  18. Optical constants of solid methane

    NASA Technical Reports Server (NTRS)

    Khare, Bishun N.; Thompson, W. R.; Sagan, C.; Arakawa, E. T.; Bruel, C.; Judish, J. P.; Khanna, R. K.; Pollack, J. B.

    1990-01-01

    Methane is the most abundant simple organic molecule in the outer solar system bodies. In addition to being a gaseous constituent of the atmospheres of the Jovian planets and Titan, it is present in the solid form as a constituent of icy surfaces such as those of Triton and Pluto, and as cloud condensate in the atmospheres of Titan, Uranus, and Neptune. It is expected in the liquid form as a constituent of the ocean of Titan. Cometary ices also contain solid methane. The optical constants for both solid and liquid phases of CH4 for a wide temperature range are needed for radiative transfer calculations, for studies of reflection from surfaces, and for modeling of emission in the far infrared and microwave regions. The astronomically important visual to near infrared measurements of solid methane optical constants are conspicuously absent from the literature. Preliminary results are presented on the optical constants of solid methane for the 0.4 to 2.6 micrometer region. Deposition onto a substrate at 10 K produces glassy (semi-amorphous) material. Annealing this material at approximately 33 K for approximately 1 hour results in a crystalline material as seen by sharper, more structured bands and negligible background extinction due to scattering. The constant k is reported for both the amorphous and the crystalline (annealed) states. Typical values (at absorption maxima) are in the .001 to .0001 range. Below lambda = 1.1 micrometers the bands are too weak to be detected by transmission through the films less than or equal to 215 micrometers in thickness, employed in the studies to date. Using previously measured values of the real part of the refractive index, n, of liquid methane at 110 K, n is computed for solid methane using the Lorentz-Lorenz relationship. Work is in progress to extend the measurements of optical constants n and k for liquid and solid to both shorter and longer wavelengths, eventually providing a complete optical constants database for

  19. Cosmologies with variable gravitational constant

    NASA Astrophysics Data System (ADS)

    Narlikar, J. V.

    1983-03-01

    In 1937 Dirac presented an argument, based on the socalled large dimensionless numbers, which led him to the conclusion that the Newtonian gravitational constant G changes with epoch. Towards the end of the last century Ernst Mach had given plausible arguments to link the property of inertia of matter to the large scale structure of the universe. Mach's principle also leads to cosmological models with a variable gravitational constant. Three cosmologies which predict a variable G are discussed in this paper both from theoretical and observational points of view.

  20. The cardiovascular effects of peroxisome proliferator-activated receptor agonists.

    PubMed

    Friedland, Sayuri N; Leong, Aaron; Filion, Kristian B; Genest, Jacques; Lega, Iliana C; Mottillo, Salvatore; Poirier, Paul; Reoch, Jennifer; Eisenberg, Mark J

    2012-02-01

    Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation. PMID:22269613

  1. [PPAR receptors and insulin sensitivity: new agonists in development].

    PubMed

    Pégorier, J-P

    2005-04-01

    Thiazolidinediones (or glitazones) are synthetic PPARgamma (Peroxisome Proliferator-Activated Receptors gamma) ligands with well recognized effects on glucose and lipid metabolism. The clinical use of these PPARgamma agonists in type 2 diabetic patients leads to an improved glycemic control and an inhanced insulin sensitivity, and at least in animal models, to a protective effect on pancreatic beta-cell function. However, they can produce adverse effects, generally mild or moderate, but some of them (mainly peripheral edema and weight gain) may conduct to treatment cessation. Several pharmacological classes are currently in pre-clinical or clinical development, with the objective to retain the beneficial metabolic properties of PPARgamma agonists, either alone or in association with the PPARalpha agonists (fibrates) benefit on lipid profile, but devoid of the side-effects on weight gain and fluid retention. These new pharmacological classes: partial PPARgamma agonists, PPARgamma antagonists, dual PPARalpha/PPARgamma agonists, pan PPARalpha/beta(delta)/gamma agonists, RXR receptor agonists (rexinoids), are presented in this review. Main results from in vitro cell experiments and animal model studies are discussed, as well as the few published short-term studies in type 2 diabetic patients. PMID:15959400

  2. Risk versus benefit considerations for the beta(2)-agonists.

    PubMed

    Kelly, H William

    2006-09-01

    Short-acting beta(2)-agonists are the mainstay of therapy for acute bronchospasm associated with asthma and chronic obstructive pulmonary disease, whereas long-acting beta(2)-agonists are used in maintaining disease control in these respiratory disorders. This review describes and compares the pharmacology of the beta(2)-agonists and explains how these differences translate into differences in efficacy and beta(2)-adrenergic-mediated adverse effects. Questions commonly asked by clinicians regarding the efficacy and safety of short- and long-acting beta(2)-agonists include issues about cardiovascular effects, tolerance to their bronchodilator and bronchoprotective effects, blunting of albuterol response by long-acting beta(2)-agonists, potential masking of worsening asthma control, and the role of long-acting beta(2)-agonists as adjunctive therapy with inhaled corticosteroids in maintaining asthma control. Pharmacogenetics may play a role in determining which patients may be at risk for a reduced response to a beta(2)-agonist. The continued use of racemic albuterol, which contains a mixture of R-albuterol and S-albuterol, has been questioned because of data from preclinical and clinical studies suggesting that S-albuterol causes proinflammatory effects and may increase bronchial hyperreactivity. The preclinical and clinical effects of these two stereoisomers are reviewed. Data describing the efficacy and safety of levalbuterol (R-albuterol) and racemic albuterol are presented. PMID:16945063

  3. Intrinsic equilibrium constants of {beta}-silicon carbide obtained from surface charge data

    SciTech Connect

    Cerovic, L.S.; Milonjic, S.K.; Kostic-Gvozdenovic, L.

    1995-11-01

    The surface charge behavior of {beta}-SiC in KNO{sub 3} electrolyte solutions is reported as a function of pH and ionic strength. The surface charge densities were obtained by potentiometric titration, and the point of zero charge of {beta}-SiC was determined by the batch equilibration method. The intrinsic equilibrium constants, describing association-dissociation of surface groups, were calculated using the site-binding model.

  4. Dissociative experience and cultural neuroscience: narrative, metaphor and mechanism.

    PubMed

    Seligman, Rebecca; Kirmayer, Laurence J

    2008-03-01

    Approaches to trance and possession in anthropology have tended to use outmoded models drawn from psychodynamic theory or treated such dissociative phenomena as purely discursive processes of attributing action and experience to agencies other than the self. Within psychology and psychiatry, understanding of dissociative disorders has been hindered by polemical "either/or" arguments: either dissociative disorders are real, spontaneous alterations in brain states that reflect basic neurobiological phenomena, or they are imaginary, socially constructed role performances dictated by interpersonal expectations, power dynamics and cultural scripts. In this paper, we outline an approach to dissociative phenomena, including trance, possession and spiritual and healing practices, that integrates the neuropsychological notions of underlying mechanism with sociocultural processes of the narrative construction and social presentation of the self. This integrative model, grounded in a cultural neuroscience, can advance ethnographic studies of dissociation and inform clinical approaches to dissociation through careful consideration of the impact of social context. PMID:18213511

  5. Strain-induced water dissociation on supported ultrathin oxide films

    PubMed Central

    Song, Zhenjun; Fan, Jing; Xu, Hu

    2016-01-01

    Controlling the dissociation of single water molecule on an insulating surface plays a crucial role in many catalytic reactions. In this work, we have identified the enhanced chemical reactivity of ultrathin MgO(100) films deposited on Mo(100) substrate that causes water dissociation. We reveal that the ability to split water on insulating surface closely depends on the lattice mismatch between ultrathin films and the underlying substrate, and substrate-induced in-plane tensile strain dramatically results in water dissociation on MgO(100). Three dissociative adsorption configurations of water with lower energy are predicted, and the structural transition going from molecular form to dissociative form is almost barrierless. Our results provide an effective avenue to achieve water dissociation at the single-molecule level and shed light on how to tune the chemical reactions of insulating surfaces by choosing the suitable substrates. PMID:26953105

  6. Being in rhythm: dissociative attunement in therapeutic process.

    PubMed

    Hopenwasser, Karen

    2008-01-01

    Dissociative attunement is a profound rhythmic encounter in therapeutic treatment. Attunement is a synchronized awareness of implicit knowing that is nonlinear and bidirectional. Empathically attuned clinicians are like microtonal tuning forks. They resonate with a variety of emotional pitches and will resonate with nuanced shifting of emotional tone. This resonance is the basis of dissociative attunement. Concepts such as empathic attunement, affect attunement, "the unthought known," "implicit relational knowing," and "a two-person unconscious" help us to understand unique aspects of projective identification, transference, and countertransference within the dissociative frame. However, "dissociative" attunements are systemically self-emergent moments in which multiple self-states are shared by means other than projection. Using clinical vignettes, I demonstrate how dissociative attunement can paradoxically appear to be misattunement. By synthesizing scientific and theoretical concepts applied to these clinical moments, we can understand dissociative attunement as a therapeutic tool as well as a pathway to vicarious traumatization. PMID:19042783

  7. Strain-induced water dissociation on supported ultrathin oxide films

    NASA Astrophysics Data System (ADS)

    Song, Zhenjun; Fan, Jing; Xu, Hu

    2016-03-01

    Controlling the dissociation of single water molecule on an insulating surface plays a crucial role in many catalytic reactions. In this work, we have identified the enhanced chemical reactivity of ultrathin MgO(100) films deposited on Mo(100) substrate that causes water dissociation. We reveal that the ability to split water on insulating surface closely depends on the lattice mismatch between ultrathin films and the underlying substrate, and substrate-induced in-plane tensile strain dramatically results in water dissociation on MgO(100). Three dissociative adsorption configurations of water with lower energy are predicted, and the structural transition going from molecular form to dissociative form is almost barrierless. Our results provide an effective avenue to achieve water dissociation at the single-molecule level and shed light on how to tune the chemical reactions of insulating surfaces by choosing the suitable substrates.

  8. Dissociative detachment relates to psychotic symptoms and personality decompensation.

    PubMed

    Allen, J G; Coyne, L; Console, D A

    1997-01-01

    Previous studies have addressed the prominence of psychotic symptoms in conjunction with multiple personality disorder (now dissociative identity disorder). The present study examines the relation between psychotic symptoms and a more pervasive form of dissociative disturbance, namely dissociative detachment. Two hundred sixty-six women in inpatient treatment for severe trauma-related disorders completed the Dissociative Experiences Scale (DES), and 102 of these patients also completed the Millon Clinical Multiaxial Inventory (MCMI-III). A factor analysis of the DES yielded two dimensions of dissociative detachment: detachment from one's own actions and detachment from the self and the environment. Each of these DES dimensions relates strongly to the thought disorder and schizotypal personality disorder scales of the MCMI-III. We propose that severe dissociative detachment, by virtue of loosening the moorings in inner and outer reality, is conducive to psychotic symptoms and personality decompensation. PMID:9406738

  9. Dissociation in individuals denying trauma exposure: findings from two samples.

    PubMed

    Briere, John; Runtz, Marsha

    2015-06-01

    A number of studies suggest that dissociation is reliably related to trauma exposure, and that inadequate regulation of posttraumatic distress may be a significant factor. We examined whether affect dysregulation predicts dissociation in those denying any lifetime exposure to trauma. These relationships were evaluated in a general population sample and a second sample of nontraumatized university students. In the first study, multivariate analyses indicated that, along with gender, affect dysregulation was a relatively strong predictor, accounting for 27% of the variance in dissociation. In the replication study, dissociation was associated with affect dysregulation, but not gender. Affect dysregulation seems to predict dissociative symptomatology in nontraumatized individuals. It is hypothesized that emotional distress, whether from trauma or other etiologies, motivates dissociation to the extent that it challenges the individual's compromised capacity for affect regulation. Treatment implications may include the potential helpfulness of interventions that increase emotion regulation skills. PMID:25974057

  10. The relationship between catatonia and dissociation: A preliminary investigation.

    PubMed

    Ross, Colin A; Browning, Elena

    2016-01-01

    Unlike the relationship between dissociation and Schneiderian first-rank symptoms, the relationship between dissociation and catatonia has not been investigated empirically. In order to gather some initial data about catatonia, dissociation, and childhood adverse experiences, we administered the Bush-Francis Catatonia Scale (BFCS), the Dissociative Experiences Scale (DES), the Adverse Childhood Experiences Questionnaire, and the Dissociative Disorders Interview Schedule to 100 inpatients in a hospital trauma program. The average DES score was 44.1 (SD = 22.4), and 86 participants were in the DES-Taxon. The average score on the BFCS was 7.7 (SD = 10.3); 81 participants scored 2 or higher, and 67 scored 5 or higher. The results showed that, in this sample, catatonic symptoms are frequent and related to adverse childhood experiences but seem to be a separate symptom category from both dissociation and psychosis. PMID:26751346

  11. Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B

    PubMed Central

    Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E.; Singh, Pratap

    2013-01-01

    TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h−1). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level < 10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action. PMID:23529133

  12. Ictal symptoms of anxiety, avoidance behaviour, and dissociation in patients with dissociative seizures

    PubMed Central

    Goldstein, L H; Mellers, J D C

    2006-01-01

    Objective To examine anxiety related seizure symptoms and avoidance behaviour in adults with dissociative (psychogenic non‐epileptic) seizures (DS) in comparison with a group suffering from partial epilepsy. Methods 25 DS and 19 epilepsy patients completed an attack symptom measure, the hospital anxiety and depression scale, the dissociative experiences scale, and the fear questionnaire. Results DS patients reported the presence of significantly greater numbers of somatic symptoms of anxiety during their attacks than the epilepsy group, despite not reporting subjectively higher levels of anxiety. The DS patients also reported higher levels of agoraphobic‐type avoidance behaviour than the epilepsy group. Measures of dissociation were higher in the DS group, who also reported greater symptoms of depression. Conclusions The findings support a model whereby DS occur as a paroxysmal, dissociative response to heightened arousal in the absence of raised general anxiety levels. The model has practical implications for clinical assessment and treatment: in clinical practice, inquiry about these symptoms may help in the diagnosis of DS; with respect to treatment, the anxiety related symptoms and avoidance behaviour prevalent in DS are a potential focus for a cognitive behavioural approach analogous to that used in the treatment of other anxiety disorders. PMID:16614021

  13. Dopamine agonist withdrawal syndrome: implications for patient care.

    PubMed

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper. PMID:23686524

  14. Imaging the molecular dynamics of dissociative electron attachment to water

    SciTech Connect

    Adaniya, Hidihito; Rudek, B.; Osipov, Timur; Haxton, Dan; Weber, Thorsten; Rescigno, Thomas N.; McCurdy, C.W.; Belkacem, Ali

    2009-10-19

    Momentum imaging experiments on dissociative electron attachment to the water molecule are combined with ab initio theoretical calculations of the angular dependence of the quantum mechanical amplitude for electron attachment to provide a detailed picture of the molecular dynamics of dissociation attachment via the two lowest energy Feshbach resonances. The combination of momentum imaging experiments and theory can reveal dissociation dynamics for which the axial recoil approximation breaks down and thus provides a powerful reaction microscope for DEA to polyatomics.

  15. Supra-physiological efficacy at GPCRs: superstition or super agonists?

    PubMed

    Langmead, Christopher J; Christopoulos, Arthur

    2013-05-01

    The concept of 'super agonism' has been described since the discovery of peptide hormone analogues that yielded greater functional responses than the endogenous agonists, in the early 1980s. It has remained an area of debate as to whether such compounds can really display greater efficacy than an endogenous agonist. However, recent pharmacological data, combined with crystal structures of different GPCR conformations and improved analytical methods for quantifying drug action, are starting to shed light on this phenomenon and indicate that super agonists may be more than superstition. PMID:23441648

  16. Constant-amplitude RC oscillator

    NASA Technical Reports Server (NTRS)

    Kerwin, W. J.; Westbrook, R. M.

    1970-01-01

    Sinusoidal oscillator has a frequency determined by resistance-capacitance /RC/ values of two charge control devices and a constant-amplitude voltage independent of frequency and RC values. RC elements provide either voltage-control, resistance-control, or capacitance-control of the frequency.

  17. Mechanical Dissociation of Retinal Neurons with Vibration

    NASA Astrophysics Data System (ADS)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  18. Autobiographical memory specificity in dissociative identity disorder.

    PubMed

    Huntjens, Rafaële J C; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes

    2014-05-01

    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specific event from memory located in time and place. Previous studies of overgeneral memory have not included patients with dissociative disorders. These patients are interesting to consider, as they are hypothesized to have the ability to selectively compartmentalize information linked to negative emotions. This study examined avoidance and overgeneral memory in patients with dissociative identity disorder (DID; n = 12). The patients completed the autobiographical memory test (AMT). Their performance was compared with control groups of posttraumatic stress disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators (n = 26). Specifically, we compared the performance of separate identity states in DID hypothesized to diverge in the use of avoidance as a coping strategy to deal with negative affect. No significant differences in memory specificity were found between the separate identities in DID. Irrespective of identity state, DID patients were characterized by a lack of memory specificity, which was similar to the lack of memory specificity found in PTSD patients. The converging results for DID and PTSD patients add empirical evidence for the role of overgeneral memory involved in the maintenance of posttraumatic psychopathology. PMID:24886016

  19. Dissociation of silica at high pressure

    NASA Astrophysics Data System (ADS)

    Hicks, Damien; Boehly, Tom

    2005-07-01

    Measurements of the temperature and optical reflectivity of quartz and fused silica under shock loading from 100 to 1000 GPa have revealed evidence for dissociation of silica between ˜150 and 400 GPa. Using attenuating laser-driven shock waves a continuous record of the temperature and reflectivity dependence on pressure has been obtained in both materials allowing the specific heat capacity and electronic conductivity to be deduced. Results show that between 150 and 400 GPa the specific heat rises significantly above that expected from the Dulong-Petit law, indicating the presence of a latent energy. Coincident with this anomalous specific heat is a rapid rise in electronic conductivity. Both these observables suggest that dissociation is occurring in the dense fluid. In addition temperature measurements near 5000 K detect a discontinuity at the melt transition, as measured earlier on gas gun experiments. This work was performed under the auspices of the US DOE by LLNL under Contract No. W-7405-ENG-48 and by the University of Rochester under Cooperative Agreement No. DE-FC03-92SF19460.

  20. Grammatical category dissociation in multilingual aphasia.

    PubMed

    Faroqi-Shah, Yasmeen; Waked, Arifi N

    2010-03-01

    Word retrieval deficits for specific grammatical categories, such as verbs versus nouns, occur as a consequence of brain damage. Such deficits are informative about the nature of lexical organization in the human brain. This study examined retrieval of grammatical categories across three languages in a trilingual person with aphasia who spoke Arabic, French, and English. In order to delineate the nature of word production difficulty, comprehension was tested, and a variety of concomitant lexical-semantic variables were analysed. The patient demonstrated a consistent noun-verb dissociation in picture naming and narrative speech, with severely impaired production of verbs across all three languages. The cross-linguistically similar noun-verb dissociation, coupled with little evidence of semantic impairment, suggests that (a) the patient has a true "nonsemantic" grammatical category specific deficit, and (b) lexical organization in multilingual speakers shares grammatical class information between languages. The findings of this study contribute to our understanding of the architecture of lexical organization in bilinguals. PMID:20830631

  1. Multigenerational Dissociation: A Framework for Building Narrative.

    PubMed

    McCollum, Sally E

    2015-01-01

    This paper presents the concept of Multigenerational Dissociation (MGD), a behavior pattern that occurs in families in which violence and abuse are re-enacted from one generation to the next, accompanied by denial that the trauma occurred, or if it did, that it was destructive. While revictimization, reenactment, and the intergenerational transmission of trauma are discussed extensively in the literature, MGD helps to view them within a broad historical framework. This is useful for conceptualizing cases therapeutically, and it can also contribute to research on dissociation and recovered memories of trauma and abuse by demonstrating the value of narrative clinical data. Case material is used to illustrate how MGD occurs in people's lives and affects their memories, demonstrating how it becomes a frame within which to convey the dynamics of how traumatic experiences are remembered. This also demonstrates that when clinicians contribute their own narrative data to research on traumatic memory, the science is more accurate, relevant, and comprehensible to clinical and nonclinical researchers. PMID:26158318

  2. Dissociative excitation study of iron pentacarbonyl molecule

    NASA Astrophysics Data System (ADS)

    Ribar, Anita; Danko, Marián; Országh, Juraj; Ferreira da Silva, Filipe; Utke, Ivo; Matejčík, Štefan

    2015-04-01

    The processes of dissociative excitation (DE) and dissociative ionisation with excitation (DIE) of iron pentacarbonyl, Fe(CO)5, have been studied using a crossed electron-molecule beam experimental apparatus (Electron Induced Fluorescence Apparatus, EIFA). Using EIFA we were able to record the emission spectrum of the molecule in the UV-VIS range, as well as the photon efficiency curves initiated by electron impact. The emission spectrum of Fe(CO)5 initiated by impact of 50 eV electrons was recorded in the spectral range between 200 nm and 470 nm. It shows a high density of emission lines and bands (mainly iron lines and carbonyl bands). Additionally, we have measured photon efficiency curves (PECs) as a function of the electron impact energy for several lines and bands. On the basis of the PECs we have discussed the reaction mechanism and the energetics of the reactions associated with the DE and DIE processes. Contribution to the Topical Issue "Elementary Processes with Atoms and Molecules in Isolated and Aggregated States", edited by Friedrich Aumayr, Bratislav Marinkovic, Štefan Matejčík, John Tanis and Kurt H. Becker.

  3. Dissociable behavioural outcomes of visual statistical learning

    PubMed Central

    Turk-Browne, Nicholas B.; Seitz, Aaron R.

    2016-01-01

    Statistical learning refers to the extraction of probabilistic relationships between stimuli and is increasingly used as a method to understand learning processes. However, numerous cognitive processes are sensitive to the statistical relationships between stimuli and any one measure of learning may conflate these processes; to date little research has focused on differentiating these processes. To understand how multiple processes underlie statistical learning, here we compared, within the same study, operational measures of learning from different tasks that may be differentially sensitive to these processes. In Experiment 1, participants were visually exposed to temporal regularities embedded in a stream of shapes. Their task was to periodically detect whether a shape, whose contrast was staircased to a threshold level, was present or absent. Afterwards, they completed a search task, where statistically predictable shapes were found more quickly. We used the search task to label shape pairs as “learned” or “non-learned”, and then used these labels to analyse the detection task. We found a dissociation between learning on the search task and the detection task where only non-learned pairs showed learning effects in the detection task. This finding was replicated in further experiments with recognition memory (Experiment 2) and associative learning tasks (Experiment 3). Taken together, these findings are consistent with the view that statistical learning may comprise a family of processes that can produce dissociable effects on different aspects of behaviour.

  4. Dissociative recombination of molecular ions with electrons

    NASA Technical Reports Server (NTRS)

    Johnsen, Rainer

    1990-01-01

    An overview is presented for the present state of the art of laboratory measurements of the dissociative recombination of molecular ions with electrons. Most work has focussed on obtaining rates and their temperature dependence, as these are of primary interest for model calculations of ionospheres. A comparison of data obtained using the microwave afterglow method, the flowing afterglow technique, and the merged beam technique shows that generally the agreement is quite good, but there are some serious discrepancies, especially in the case of H(3+) recombination, that need to be resolved. Results of some earlier experimental work need to be reexamined in the light of more recent developments. Such cases are pointed out and a compilation of rate coefficients that have withstood scrutiny is presented. Recent advances in experimental methods, such as the use of laser-in-duced fluorescence, make it possible to identify some neutral products of dissociative recombination. What has been done so far and what results one might expect from future work are briefly reviewed.

  5. Dissociation of methane under high pressure.

    PubMed

    Gao, Guoying; Oganov, Artem R; Ma, Yanming; Wang, Hui; Li, Peifang; Li, Yinwei; Iitaka, Toshiaki; Zou, Guangtian

    2010-10-14

    Methane is an extremely important energy source with a great abundance in nature and plays a significant role in planetary physics, being one of the major constituents of giant planets Uranus and Neptune. The stable crystal forms of methane under extreme conditions are of great fundamental interest. Using the ab initio evolutionary algorithm for crystal structure prediction, we found three novel insulating molecular structures with P2(1)2(1)2(1), Pnma, and Cmcm space groups. Remarkably, under high pressure, methane becomes unstable and dissociates into ethane (C(2)H(6)) at 95 GPa, butane (C(4)H(10)) at 158 GPa, and further, carbon (diamond) and hydrogen above 287 GPa at zero temperature. We have computed the pressure-temperature phase diagram, which sheds light into the seemingly conflicting observations of the unusually low formation pressure of diamond at high temperature and the failure of experimental observation of dissociation at room temperature. Our results support the idea of diamond formation in the interiors of giant planets such as Neptune. PMID:20950018

  6. Dissociation of methane into hydrocarbons at extreme (planetary) pressure and temperature.

    PubMed

    Ancilotto, F; Chiarotti, G L; Scandolo, S; Tosatti, E

    1997-02-28

    Constant-pressure, first-principles molecular dynamic simulations were used to investigate the behavior of methane at high pressure and temperature. Contrary to the current interpretation of shock-wave experiments, the simulations suggest that, below 100 gigapascals, methane dissociates into a mixture of hydrocarbons, and it separates into hydrogen and carbon only above 300 gigapascals. The simulation conditions (100 to 300 gigapascals; 4000 to 5000 kelvin) were chosen to follow the isentrope in the middle ice layers of Neptune and Uranus. Implications on the physics of these planets are discussed. PMID:9036849

  7. The vibrational dynamics of 3D HOCl above dissociation

    SciTech Connect

    Lin, Yi-Der; Reichl, L. E.; Jung, Christof

    2015-03-28

    We explore the classical vibrational dynamics of the HOCl molecule for energies above the dissociation energy of the molecule. Above dissociation, we find that the classical dynamics is dominated by an invariant manifold which appears to stabilize two periodic orbits at energies significantly above the dissociation energy. These stable periodic orbits can hold a large number of quantum states and likely can support a significant quasibound state of the molecule, well above the dissociation energy. The classical dynamics and the lifetime of quantum states on the invariant manifold are determined.

  8. Childhood maltreatment and intimate partner violence in dissociative disorder patients

    PubMed Central

    Webermann, Aliya R.; Brand, Bethany L.; Chasson, Gregory S.

    2014-01-01

    Background Childhood maltreatment (CM) is a risk factor for subsequent intimate partner violence (IPV) in adulthood, with high rates of retrospectively reported CM among IPV victims and perpetrators. A theorized mechanism of the link between CM and IPV is dissociation. Dissociation may allow perpetrators of violence to remain emotionally distant from their behavior and minimize empathy toward those they victimize, enabling them to commit acts of violence similar to their own experiences. Indeed, elevated rates of dissociation and dissociative disorders (DD) have been found among IPV survivors and perpetrators. In addition, in pilot studies, DD clinicians have reported high levels of violent behavior among DD patients. Objective The present study investigates IPV among DD patients with Dissociative Identity Disorder and Dissociative Disorder Not Otherwise Specified, a group with CM rates of 80–95% and severe dissociative symptoms. Methods DD clinicians reported on rates of CM and IPV among 275 DD patients in outpatient treatment. DD patients also completed a self-report measure of dissociation. Analyses assessed the associations between CM typologies and IPV, as well as trait dissociation and IPV. Results Physical and emotional child abuse were associated with physical IPV, and childhood witnessing of domestic violence (DV) and childhood neglect were associated with emotional IPV. Conclusions The present study is the first to provide empirical support for a possible CM to adult IPV developmental trajectory among DD patients. Future research is needed to better understand the link between CM and IPV among those with trauma and DD. PMID:25279109

  9. Autocatalytic water dissociation on Cu(110) at near ambient conditions

    SciTech Connect

    Mulleregan, Alice; Andersson, Klas; Ketteler, Guido; Bluhm, Hendrik; Yamamoto, Susumu; Ogasawara, Hirohito; Pettersson, Lars G.M.; Salmeron, Miquel; Nilsson, Anders

    2007-05-16

    Autocatalytic dissociation of water on the Cu(110) metal surface is demonstrated based on X-ray photoelectron spectroscopy studies carried out in-situ under near ambient conditions of water vapor pressure (1 Torr) and temperature (275-520 K). The autocatalytic reaction is explained as the result of the strong hydrogen-bond in the H{sub 2}O-OH complex of the dissociated final state, which lowers the water dissociation barrier according to the Broensted-Evans-Polanyi relations. A simple chemical bonding picture is presented which predicts autocatalytic water dissociation to be a general phenomenon on metal surfaces.

  10. Psychometric validation of the State Scale of Dissociation (SSD).

    PubMed

    Krüger, Christa; Mace, Chris J

    2002-03-01

    Although dissociative phenomena are often transient features of mental states, existing measures of dissociation are designed to measure enduring traits. A new present-state self-report measure, sensitive to changes in dissociative states, was therefore developed and psychometrically validated. Fifty-six items were formulated to measure state features, and sorted according to seven subscales: derealization, depersonalization, identity confusion, identity alteration, conversion, amnesia and hypermnesia. The State Scale of Dissociation (SSD) was administered with other psychiatric scales (DES, BDI, BAI, SCI-PANSS) to 130 participants with DSM-IV major depressive disorder schizophrenia, alcohol withdrawal, dissociative disorders and controls. In these sample populations, the SSD was demonstrated as a valid and reliable measure of changes in and the severity of dissociative states. Discriminant validity, content, concurrent, predictive, internal criterion-related, internal construct and convergent validities, and internal consistency and split-half reliability were confirmed statistically. Clinical observations of dissociative states, and their comorbidity with symptoms of depression and psychotic illness, were confirmed empirically. The SSD, an acceptable, valid and reliable scale measuring state features of dissociation at the time of completion, was obtained. This is a prerequisite for further investigation of correlations between changes in dissociative states and concurrent physiological parameters. PMID:12006198

  11. The vibrational dynamics of 3D HOCl above dissociation

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Der; Reichl, L. E.; Jung, Christof

    2015-03-01

    We explore the classical vibrational dynamics of the HOCl molecule for energies above the dissociation energy of the molecule. Above dissociation, we find that the classical dynamics is dominated by an invariant manifold which appears to stabilize two periodic orbits at energies significantly above the dissociation energy. These stable periodic orbits can hold a large number of quantum states and likely can support a significant quasibound state of the molecule, well above the dissociation energy. The classical dynamics and the lifetime of quantum states on the invariant manifold are determined.

  12. The Vibrational Dynamics of 3D HOCl Above Dissociation

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Der; Reichl, Linda; Jung, Christof

    2015-03-01

    We have analyzed the vibrational dynamics of HOCl above dissociation using a 3D energy surface which governs the vibrational dynamics of HOCl above dissociation. The dynamics is dominated by an invariant manifold which is transversally unstable for small spacing between Cl and HO complex, and stable for large spacing. Above dissociation, the InM separates two mirror image periodic orbits, embedded in a large chaotic sea, that can hold a large number of quantum states. These periodic orbits have the capability of forming significant quasibound states of the molecule above dissociation. Welch Foundation.

  13. Dissociability of free and peptidyl-tRNA bound ribosomes.

    PubMed

    Surguchov, A P; Fominykch, E S; Lyzlova, L V

    1978-06-16

    The influence of peptidyl-tRNA on the dissociation of yeast 80 S ribosomes into subunits was studied. For this purpose temperature-sensitive (ts) suppressor strain of yeast Saccharomyces cervisiae carrying a defect in peptide chain termination was used. It was found that peptidyl-tRNA did not influence the dissociation of ribosomes either at high salt concentration or in the presence of dissociation factor (DF) from yeast. After dissociation of yeast ribosomes in 0.5 M KCl, peptidyl-tRNA remains bound to the 60 S subunit. Some characteristics of the termination process and release of nascent polypeptides from yeast ribosomes are discussed. PMID:355860

  14. Dissociation curves of diatomic molecules: A DC-DFT study

    SciTech Connect

    Sim, Eunji; Kim, Min-Cheol; Burke, Kieron

    2015-12-31

    We investigate dissociation of diatomic molecules using standard density functional theory (DFT) and density-corrected density functional theory (DC-DFT) compared with CCSD(T) results as reference. The results show the difference between the HOMO values of dissociated atomic species often can be used as an indicator whether DFT would predict the correct dissociation limit. DFT predicts incorrect dissociation limits and charge distribution in molecules or molecular ions when the fragments have large HOMO differences, while DC-DFT and CCSD(T) do not. The criteria for large HOMO difference is about 2 ∼ 4 eV.

  15. Controls on Gas Hydrate Formation and Dissociation

    SciTech Connect

    Miriam Kastner; Ian MacDonald

    2006-03-03

    The main objectives of the project were to monitor, characterize, and quantify in situ the rates of formation and dissociation of methane hydrates at and near the seafloor in the northern Gulf of Mexico, with a focus on the Bush Hill seafloor hydrate mound; to record the linkages between physical and chemical parameters of the deposits over the course of one year, by emphasizing the response of the hydrate mound to temperature and chemical perturbations; and to document the seafloor and water column environmental impacts of hydrate formation and dissociation. For these, monitoring the dynamics of gas hydrate formation and dissociation was required. The objectives were achieved by an integrated field and laboratory scientific study, particularly by monitoring in situ formation and dissociation of the outcropping gas hydrate mound and of the associated gas-rich sediments. In addition to monitoring with the MOSQUITOs, fluid flow rates and temperature, continuously sampling in situ pore fluids for the chemistry, and imaging the hydrate mound, pore fluids from cores, peepers and gas hydrate samples from the mound were as well sampled and analyzed for chemical and isotopic compositions. In order to determine the impact of gas hydrate dissociation and/or methane venting across the seafloor on the ocean and atmosphere, the overlying seawater was sampled and thoroughly analyzed chemically and for methane C isotope ratios. At Bush hill the pore fluid chemistry varies significantly over short distances as well as within some of the specific sites monitored for 440 days, and gas venting is primarily focused. The pore fluid chemistry in the tub-warm and mussel shell fields clearly documented active gas hydrate and authigenic carbonate formation during the monitoring period. The advecting fluid is depleted in sulfate, Ca Mg, and Sr and is rich in methane; at the main vent sites the fluid is methane supersaturated, thus bubble plumes form. The subsurface hydrology exhibits both

  16. Products of Dissociative Recombination in the Ionosphere

    NASA Technical Reports Server (NTRS)

    Cosby, Philip

    1996-01-01

    SRI International undertook a novel experimental measurement of the product states formed by dissociative recombination (DR) of O2(+), NO(+), and N2(+) as a function of both electron energy and reactant ion vibrational level. For these measurements we used a recently developed experimental technique for measuring dissociation product distributions that allows both the branching ratios to be accurately determined and the electronic and rovibrational state composition of the reactant ions to be specified. DR is the dominant electron loss mechanism in all regions of the ionosphere. In this process, electron attachment to the molecular ion produces an unstable neutral molecule that rapidly dissociates. For a molecular ion such as O2(+), the dissociation recombination reaction is (1) O2(+) + e yields O + O + W. The atomic products of this reaction, in this case two oxygen atoms, can be produced in a variety of excited states and with a variety of kinetic energies, as represented by W in Eq. (1). These atoms are not only active in the neutral chemistry of the ionosphere, but are also especially important because their optical emissions are often used to infer in situ concentrations of the parent molecular ion and ambient electron densities. Many laboratory measurements have been made of DR reaction rates under a wide range of electron temperatures, but very little is known about the actual distributions among the final states of the atomic products. This lack of knowledge seriously limits the validity and effectiveness of efforts to model both natural and man-made ionospheric disturbances. Bates recently identified major deficiencies in the currently accepted branching ratios for O2(+) as they relate to blue and green line emission measurements in the nocturnal F-region. During our two-year effort, we partially satisfied our ambitious goals. We constructed and operated a variable pressure, electron-impact ion source and a high pressure, hollow-cathode discharge ion

  17. The 1% concordance Hubble constant

    SciTech Connect

    Bennett, C. L.; Larson, D.; Weiland, J. L.; Hinshaw, G.

    2014-10-20

    The determination of the Hubble constant has been a central goal in observational astrophysics for nearly a hundred years. Extraordinary progress has occurred in recent years on two fronts: the cosmic distance ladder measurements at low redshift and cosmic microwave background (CMB) measurements at high redshift. The CMB is used to predict the current expansion rate through a best-fit cosmological model. Complementary progress has been made with baryon acoustic oscillation (BAO) measurements at relatively low redshifts. While BAO data do not independently determine a Hubble constant, they are important for constraints on possible solutions and checks on cosmic consistency. A precise determination of the Hubble constant is of great value, but it is more important to compare the high and low redshift measurements to test our cosmological model. Significant tension would suggest either uncertainties not accounted for in the experimental estimates or the discovery of new physics beyond the standard model of cosmology. In this paper we examine in detail the tension between the CMB, BAO, and cosmic distance ladder data sets. We find that these measurements are consistent within reasonable statistical expectations and we combine them to determine a best-fit Hubble constant of 69.6 ± 0.7 km s{sup –1} Mpc{sup –1}. This value is based upon WMAP9+SPT+ACT+6dFGS+BOSS/DR11+H {sub 0}/Riess; we explore alternate data combinations in the text. The combined data constrain the Hubble constant to 1%, with no compelling evidence for new physics.

  18. Optical constants of solid methane

    SciTech Connect

    Khare, B.N.; Thompson, W.R.; Sagan, C. . Lab. for Planetary Studies); Arakawa, E.T.; Bruel, C.; Judish, J.P. ); Khanna, R.K. . Dept. of Chemistry and Biochemistry); Pollack, J.B. . Ames Research Center)

    1989-01-01

    Methane is the most abundant simple organic molecule in the outer solar system bodies. In addition to being a gaseous constituent of the atmospheres of the Jovian planets and Titan, it is present in the solid form as a constituent of icy surfaces such as those of Triton and Pluto, and as cloud condensate in the atmospheres of Titan, Uranus, and Neptune. It is expected in the liquid form as a constituent of the ocean of Titan. Cometary ices also contain solid methane. The optical constants for both solid and liquid phases of CH{sub 4} for a wide temperature range are needed for radiative transfer calculations, for studies of reflection from surfaces, and for modeling of emission in the far infrared and microwave regions. The astronomically important visual to near infrared measurements of solid methane optical constants are conspicuously absent from the literature. We present preliminary results of the optical constants of solid methane for the 0.4 {mu}m to 2.6 {mu}m region. We report k for both the amorphous and the crystalline (annealed) states. Using our previously measured values of the real part of the refractive index, n, of liquid methane at 110{degree}K (Bull. Am. Phys. Soc.31, 700 (1986)) we compute n for solid methane using the Lorentz-Lorentz relationship. Work is in progress to extend the measurements of optical constants n and k for liquid and solid to both shorter and longer wavelengths, eventually providing a complete optical constants database for condensed CH{sub 4}. 33 refs., 6 figs., 2 tabs.

  19. Thermodynamics of the dissociation of boric acid in synthetic seawater from 273.15 to 318.15 K

    NASA Astrophysics Data System (ADS)

    Dickson, Andrew G.

    1990-05-01

    E.m.f. measurements have been made using the cell: Pt | H 2(g,101.325 kPa) | borax in synthetic seawater | AgCl; Ag over the temperature range 273.15-318.15 K, and at five salinities from 5 to 45. The results have been used to calculate the stoichiometric (ionic medium) dissociation constant for boric acid in seawater media on the "total" hydrogen ion scale.

  20. New Quasar Studies Keep Fundamental Physical Constant Constant

    NASA Astrophysics Data System (ADS)

    2004-03-01

    Very Large Telescope sets stringent limit on possible variation of the fine-structure constant over cosmological time Summary Detecting or constraining the possible time variations of fundamental physical constants is an important step toward a complete understanding of basic physics and hence the world in which we live. A step in which astrophysics proves most useful. Previous astronomical measurements of the fine structure constant - the dimensionless number that determines the strength of interactions between charged particles and electromagnetic fields - suggested that this particular constant is increasing very slightly with time. If confirmed, this would have very profound implications for our understanding of fundamental physics. New studies, conducted using the UVES spectrograph on Kueyen, one of the 8.2-m telescopes of ESO's Very Large Telescope array at Paranal (Chile), secured new data with unprecedented quality. These data, combined with a very careful analysis, have provided the strongest astronomical constraints to date on the possible variation of the fine structure constant. They show that, contrary to previous claims, no evidence exist for assuming a time variation of this fundamental constant. PR Photo 07/04: Relative Changes with Redshift of the Fine Structure Constant (VLT/UVES) A fine constant To explain the Universe and to represent it mathematically, scientists rely on so-called fundamental constants or fixed numbers. The fundamental laws of physics, as we presently understand them, depend on about 25 such constants. Well-known examples are the gravitational constant, which defines the strength of the force acting between two bodies, such as the Earth and the Moon, and the speed of light. One of these constants is the so-called "fine structure constant", alpha = 1/137.03599958, a combination of electrical charge of the electron, the Planck constant and the speed of light. The fine structure constant describes how electromagnetic forces hold

  1. Relamorelin: A Novel Gastrocolokinetic Synthetic Ghrelin Agonist

    PubMed Central

    Camilleri, Michael; Acosta, Andres

    2015-01-01

    Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately 6-fold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a pre-specified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders. PMID:25545036

  2. Research on the production of hydrogen by direct thermal dissociation of water vapor

    SciTech Connect

    Lapicque, F.; Abdul-Aziz, G.; Anthony, A.M.; Baumard, B.; Cales, B.; Lede, J.; Ledoux, M.; Puechberty, D.; Villermaux, J.

    1985-04-01

    The partial dissociation of steam to the extent of a few percent at temperatures above 2000K is predicted thermodynamically. Dissociation probably occurs by a partially heterogeneous mechanism between 1,700 K and 1,900 K, and by a homogeneous mechanism above 2,000 K. The kinetic constants for the corresponding elementary processes are presented. These thermal splitting reactions can be utilized either by separating oxygen across a semipermeable membrane or by rapid cooling of the reacting mixture. In order to use the first method, materials based on solid solutions of the ternary system ZrO/sub 2/-CeO/sub 2/-Y/sub 2/O/sub 3/ were developed. Their properties were studied and taken advantage of to make membranes semipermeable to oxygen. The second method uses a dissociation reactor (a zirconia nozzle heated by concentrated thermal radiation followed by a quenching zone (mixing with cold gas). After optimizing the nozzle shape and the process of quenching, an appreciable production of hydrogen was achieved (two liters per hour per 700 W of thermal input). The reactor was tested successfully at the 2-kW Odeillo solar furnace.

  3. Statistical Thermodynamic Model for Surface Tension of Aqueous Organic Acids with Consideration of Partial Dissociation.

    PubMed

    Boyer, Hallie C; Dutcher, Cari S

    2016-06-30

    With statistical mechanics, an isotherm-based surface tension model for single solute aqueous solutions was derived previously (Wexler et al. J. Phys. Chem. Lett. 2013) for the entire concentration range, from infinite dilution to pure liquid solute, as a function of solute activity. In recent work (Boyer et al. J. Phys. Chem. Lett. 2015), empirical model parameters were reduced through physicochemical interpretations of both electrolyte and organic solutes, enabling surface tension predictions for systems where there is little or no data. The prior binary model is extended in the current work for the first time to treat multicomponent systems to predict surface tensions of partially dissociating organic acids (acetic, butyric, citric, formic, glutaric, maleic, malic, malonic, oxalic, propionic, and succinic acids). These organic acids are especially applicable to the study of atmospheric aqueous aerosols, due to their abundance in the atmosphere. In the model developed here, surface tension depends explicitly on activities of both the neutral organic and deprotonated components of the acid. The relative concentrations of the nondissociated and dissociated mole fractions are found using known dissociation constants. Model parameters strongly depend on molecular size, number of functional groups, O:C ratio, and number of carbons. For all organic acids in this study, fully predictive modeling of surface tensions is demonstrated. PMID:27219322

  4. The Effect of Carbon Monoxide Co-Adsorption on Ni-Catalysed Water Dissociation

    PubMed Central

    Mohsenzadeh, Abas; Borjesson, Anders; Wang, Jeng-Han; Richards, Tobias; Bolton, Kim

    2013-01-01

    The effect of carbon monoxide (CO) co-adsorption on the dissociation of water on the Ni(111) surface has been studied using density functional theory. The structures of the adsorbed water molecule and of the transition state are changed by the presence of the CO molecule. The water O–H bond that is closest to the CO is lengthened compared to the structure in the absence of the CO, and the breaking O–H bond in the transition state structure has a larger imaginary frequency in the presence of CO. In addition, the distances between the Ni surface and H2O reactant and OH and H products decrease in the presence of the CO. The changes in structures and vibrational frequencies lead to a reaction energy that is 0.17 eV less exothermic in the presence of the CO, and an activation barrier that is 0.12 eV larger in the presence of the CO. At 463 K the water dissociation rate constant is an order of magnitude smaller in the presence of the CO. This reveals that far fewer water molecules will dissociate in the presence of CO under reaction conditions that are typical for the water-gas-shift reaction. PMID:24287907

  5. Novel 2-alkyl-1-ethylpyridinium ionic liquids: synthesis, dissociation energies and volatility.

    PubMed

    Vilas, Miguel; Rocha, Marisa A A; Fernandes, Ana M; Tojo, Emilia; Santos, Luís M N B F

    2015-01-28

    This work presents the synthesis, volatility study and electrospray ionization mass spectrometry with energy-variable collision induced dissociation of the isolated [(cation)2(anion)](+) of a novel series of 2-alkyl-1-ethyl pyridinium based ionic liquids, [(2)CN-2(1)C2Py][NTf2]. Compared to the imidazolium based ionic liquids, the new ionic liquid series presents a higher thermal stability and lower volatility. The [(cation)2(anion)](+) collision induced dissociation energies of both [(2)CN-2(1)C2Py][NTf2] and [CNPy][NTf2] pyridinium series show an identical trend with a pronounced decrease of the relative cation-anion interaction energy towards an almost constant value for N = 6. It was found that the lower volatility of [(2)CN-2(1)C2Py][NTf2] with a shorter alkyl chain length is due to its higher enthalpy of vaporization. Starting from [(2)C3(1)C2Py][NTf2], the lower volatility is governed by the combination of slightly lower entropies and higher enthalpies of vaporization, an indication of a higher structural disorder of the pyridinium based ionic liquids than the imidazolium based ionic liquids. Dissociation energies and volatility trends support the cohesive energy interpretation model based on the overlapping of the electrostatic and van der Waals functional interaction potentials. PMID:25493639

  6. MEASUREMENT OF DRUG-PROTEIN DISSOCIATION RATES BY HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY AND PEAK PROFILING

    PubMed Central

    Schiel, John E.; Ohnmacht, Corey M.; Hage, David S.

    2012-01-01

    The rate at which a drug or other small solute interacts with a protein is important in understanding the biological and pharmacokinetic behavior of these agents. One approach that has been developed for examining these rates involves the use of high-performance affinity chromatography (HPAC) and estimates of band-broadening through peak profiling. Previous work with this method has been based on a comparison of the statistical moments for a retained analyte versus non-retained species at a single, high flow rate to obtain information on stationary phase mass transfer. In this study an alternative approach was created that allows a broad range of flow rates to be used for examining solute-protein dissociation rates. Chromatographic theory was employed to derive equations that could be used with this approach on a single column, as well as with multiple columns to evaluate and correct for the impact of stagnant mobile phase mass transfer. The interaction of L-tryptophan with human serum albumin was used as a model system to test this method. A dissociation rate constant of 2.7 (± 0.2) s−1 was obtained by this approach at pH 7.4 and 37°C, which was in good agreement with previous values determined by other methods. The techniques described in this report can be applied to other biomolecular systems and should be valuable for the determination of drug-protein dissociation rates. PMID:19422253

  7. Reactive molecular dynamic simulations of hydrocarbon dissociations on Ni(111) surfaces

    NASA Astrophysics Data System (ADS)

    Liu, Bin; Lusk, Mark T.; Ely, James F.

    2012-03-01

    Empirical potential parameters for H, C and Ni elements have been developed for the ReaxFF force field in order to study the decomposition of small hydrocarbon molecules on nickel using molecular dynamics simulations. These parameters were optimized using the geometrical and energetic information obtained from density functional (DFT) calculations on a subset of hydrogen and methane reactions with nickel (111) surfaces. The resulting force field was then used to obtain a molecular perspective of the dynamics of the methane dissociative adsorption on Ni(111) as well as two other small alkane molecules, ethane and n-butane. NVT simulations of dissociative adsorption of methane over a range of temperatures enabled the estimation of the sticking coefficient for the adsorption as well as the activation energy of the first C-H bond breaking. The rate constants of each elementary step (both forward and reverse) of CHx dissociation on Ni(111) were obtained by monitoring the surface species and a microkinetic model was constructed as a result. Qualitative analyses of the simulations of ethane and n-butane decompositions on Ni(111) demonstrate that such reactive MD technique can also be used to obtain useful information on complex reaction networks.

  8. Evidence for broken ergodicity due to chemical alloying from the dissociation kinetics of binary clusters.

    PubMed

    Calvo, F; Yurtsever, E

    2014-06-01

    The interplay between thermal relaxation and statistical dissociation in binary Morse clusters (AB)N has been investigated using numerical simulations and simple statistical approaches, for a variety of interaction parameters covering miscible and non-miscible regimes. While all clusters exhibit a core/shell phase separation pattern in their most stable, T = 0 structure, different melting mechanisms are identified depending on the ranges and their mismatch, including two-step melting of the surface and the core or premelting as alloying. The preference for emitting A or B particles upon evaporation has been evaluated assuming that the cluster is either thermally equilibrated or vibrationally excited in its ground state structure, and compared to the predictions of the Weisskopf theory. The variations of the dissociation rate constants with increasing energy and the branching ratio between the two channels show significant differences in both cases, especially when the clusters are miscible and bound by short-range forces, which indicates that the time scale for evaporation is much shorter than the equilibration time. Our results suggest that dissociation properties could be used to test the ergodic hypothesis in such compounds. PMID:24908002

  9. Evidence for broken ergodicity due to chemical alloying from the dissociation kinetics of binary clusters

    NASA Astrophysics Data System (ADS)

    Calvo, F.; Yurtsever, E.

    2014-06-01

    The interplay between thermal relaxation and statistical dissociation in binary Morse clusters (AB)N has been investigated using numerical simulations and simple statistical approaches, for a variety of interaction parameters covering miscible and non-miscible regimes. While all clusters exhibit a core/shell phase separation pattern in their most stable, T = 0 structure, different melting mechanisms are identified depending on the ranges and their mismatch, including two-step melting of the surface and the core or premelting as alloying. The preference for emitting A or B particles upon evaporation has been evaluated assuming that the cluster is either thermally equilibrated or vibrationally excited in its ground state structure, and compared to the predictions of the Weisskopf theory. The variations of the dissociation rate constants with increasing energy and the branching ratio between the two channels show significant differences in both cases, especially when the clusters are miscible and bound by short-range forces, which indicates that the time scale for evaporation is much shorter than the equilibration time. Our results suggest that dissociation properties could be used to test the ergodic hypothesis in such compounds.

  10. Pair interactions in polyelectrolyte-nanoparticle systems: Influence of dielectric inhomogeneities and the partial dissociation of polymers and nanoparticles

    SciTech Connect

    Pryamitsyn, Victor; Ganesan, Venkat

    2015-10-28

    We study the effective pair interactions between two charged spherical particles in polyelectrolyte solutions using polymer self-consistent field theory. In a recent study [V. Pryamitsyn and V. Ganesan, Macromolecules 47, 6095 (2015)], we considered a model in which the particles possess fixed charge density, the polymers contain a prespecified amount of dissociated charges and, the dielectric constant of the solution was assumed to be homogeneous in space and independent of the polymer concentration. In this article, we present results extending our earlier model to study situations in which either or both the particle and the polymers possess partially dissociable groups. Additionally, we also consider the case when the dielectric constant of the solution depends on the local concentration of the polymers and when the particle’s dielectric constant is lower than that of the solvent. For each case, we quantify the polymer-mediated interactions between the particles as a function of the polymer concentrations and the degree of dissociation of the polymer and particles. Consistent with the results of our previous study, we observe that the polymer-mediated interparticle interactions consist of a short-range attraction and a long-range repulsion. The partial dissociablity of the polymer and particles was seen to have a strong influence on the strength of the repulsive portion of the interactions. Rendering the dielectric permittivity to be inhomogeneous has an even stronger effect on the repulsive interactions and results in changes to the qualitative nature of interactions in some parametric ranges.

  11. Selecting agonists from single cells infected with combinatorial antibody libraries.

    PubMed

    Zhang, Hongkai; Yea, Kyungmoo; Xie, Jia; Ruiz, Diana; Wilson, Ian A; Lerner, Richard A

    2013-05-23

    We describe a system for direct selection of antibodies that are receptor agonists. Combinatorial antibody libraries in lentiviruses are used to infect eukaryotic cells that contain a fluorescent reporter system coupled to the receptor for which receptor agonist antibodies are sought. In this embodiment of the method, very large numbers of candidate antibodies expressing lentivirus and eukaryotic reporter cells are packaged together in a format where each is capable of replication, thereby forging a direct link between genotype and phenotype. Following infection, cells that fluoresce are sorted and the integrated genes encoding the agonist antibodies recovered. We validated the system by illustrating its ability to generate rapidly potent antibody agonists that are complete thrombopoietin phenocopies. The system should be generalizable to any pathway where its activation can be linked to production of a selectable phenotype. PMID:23706638

  12. Therapeutic Potential of 5-HT6 Receptor Agonists.

    PubMed

    Karila, Delphine; Freret, Thomas; Bouet, Valentine; Boulouard, Michel; Dallemagne, Patrick; Rochais, Christophe

    2015-10-22

    Given its predominant expression in the central nervous system (CNS), 5-hydroxytryptamine (5-HT: serotonin) subtype 6 receptor (5-HT6R) has been considered as a valuable target for the development of CNS drugs with limited side effects. After 2 decades of intense research, numerous selective ligands have been developed to target this receptor; this holds potential interest for the treatment of neuropathological disorders. In fact, some agents (mainly antagonists) are currently undergoing clinical trial. More recently, a series of potent and selective agonists have been developed, and preclinical studies have been conducted that suggest the therapeutic interest of 5-HT6R agonists. This review details the medicinal chemistry of these agonists, highlights their activities, and discusses their potential for treating cognitive issues associated with Alzheimer's disease (AD), depression, or obesity. Surprisingly, some studies have shown that both 5-HT6R agonists and antagonists exert similar procognitive activities. This article summarizes the hypotheses that could explain this paradox. PMID:26099069

  13. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    PubMed

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. PMID:20579229

  14. Selective 5-HT2C agonists as potential antidepressants.

    PubMed

    Leysen, D C

    1999-02-01

    The antidepressants currently used need improvement, especially in terms of efficacy, relapse rate and onset of action. In this review the clinical and experimental data which support the rationale for 5-HT2C agonists in the treatment of depression are listed. Next, the results obtained with the non-selective 5-HT2C agonists on the market and in clinical development are described. Finally, the preclinical data on the more selective 5-HT2C agonists are summarized. These recent preclinical results reveal a greater potency and effect size compared to fluoxetine, good tolerability and no evidence of tolerance development. Selective 5-HT2C agonists might become innovative drugs for the treatment of depression, panic, obsessive-compulsive disorder (OCD), some forms of aggression and eating disorders. PMID:16160946

  15. Anomalously slow cyanide binding to Glycera dibranchiata monomer methemoglobin component II: Implication for the equilibrium constant

    SciTech Connect

    Mintorovitch, J.; Satterlee, J.D. )

    1988-10-18

    In comparison to sperm whale metmyoglobin, metleghemoglobin {alpha}, methemoglobins, and heme peroxidases, the purified Glycera dibranchiata monomer methemoglobin component II exhibits anomalously slow cyanide ligation kinetics. For the component II monomer methemoglobin this reaction has been studied under pseudo-first-order conditions at pH 6.0, 7.0, 8.0, and 9.0, employing 100-250-fold mole excesses of potassium cyanide at each pH. The analysis shows that the concentration-independent bimolecular rate constant is small in comparison to those of the other heme proteins. Furthermore, the results show that the dissociation rate is extremely slow. Separation of the bimolecular rate constant into contributions from k{sub CN{sup {minus}}} (the rate constant for CN{sup {minus}} binding) and from k{sub HCN} (the rate constant for HCN binding) shows that the former is approximately 90 times greater. These results indicate that cyanide ligation reactions are not instantaneous for this protein, which is important for those attempting to study the ligand-binding equilibria. From the results presented here the authors estimate that the actual equilibrium dissociation constant (K{sub D}) for cyanide binding to this G. dibranchiata monomer methemoglobin has a numerical upper limit that is at least 2 orders of magnitude smaller than the value reported before the kinetic results were known.

  16. Agonist pharmacology of two Drosophila GABA receptor splice variants.

    PubMed Central

    Hosie, A. M.; Sattelle, D. B.

    1996-01-01

    1. The Drosophila melanogaster gamma-aminobutyric acid (GABA) receptor subunits, RDLac and DRC 17-1-2, form functional homo-oligomeric receptors when heterologously expressed in Xenopus laevis oocytes. The subunits differ in only 17 amino acids, principally in regions of the N-terminal domain which determine agonist pharmacology in vertebrate ionotropic neurotransmitter receptors. A range of conformationally restricted GABA analogues were tested on the two homo-oligomers and their agonists pharmacology compared with that of insect and vertebrate iontropic GABA receptors. 2. The actions of GABA, isoguvacine and isonipecotic acid on RDLac and DRC 17-1-2 homo-oligomers were compared, by use of two-electrode voltage-clamp. All three compounds were full agonists of both receptors, but were 4-6 fold less potent agonists of DRC 17-1-2 homo-oligomers than of RDLac. However, the relative potencies of these agonists on each receptor were very similar. 3. A more complete agonist profile was established for RDLac homo-oligomers. The most potent agonists of these receptors were GABA, muscimol and trans-aminocrotonic acid (TACA), which were approximately equipotent. RDLac homo-oligomers were fully activated by a range of GABA analogues, with the order of potency: GABA > ZAPA ((Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid) > isoguvacine > imidazole-4-acetic acid > or = isonipecotic acid > or = cis-aminocrotonic acid (CACA) > beta-alanine. 3-Aminopropane sulphonic acid (3-APS), a partial agonist of RDLac homo-oligomers, was the weakest agonist tested and 100 fold less potent than GABA. 4. SR95531, an antagonist of vertebrate GABAA receptors, competitively inhibited the GABA responses of RDLac homo-oligomers, which have previously been found to insensitive to bicuculline. However, its potency (IC50 500 microM) was much reduced when compared to GABAA receptors. 5. The agonist pharmacology of Drosophila RDLac homo-oligomers exhibits aspects of the characteristic pharmacology of

  17. Quaternions as astrometric plate constants

    NASA Technical Reports Server (NTRS)

    Jefferys, William H.

    1987-01-01

    A new method for solving problems in relative astrometry is proposed. In it, the relationship between the measured quantities and the components of the position vector of a star is modeled using quaternions, in effect replacing the plate constants of a standard four-plate-constant solution with the four components of a quaternion. The method allows a direct solution for the position vectors of the stars, and hence for the equatorial coordinates. Distortions, magnitude, and color effects are readily incorporated into the formalism, and the method is directly applicable to overlapping-plate problems. The advantages of the method include the simplicity of the resulting equations, their freedom from singularities, and the fact that trigonometric functions and tangential point transformations are not needed to model the plate material. A global solution over the entire sky is possible.

  18. Sleep attacks in patients taking dopamine agonists: review

    PubMed Central

    Homann, Carl Nikolaus; Wenzel, Karoline; Suppan, Klaudia; Ivanic, Gerd; Kriechbaum, Norbert; Crevenna, Richard; Ott, Erwin

    2002-01-01

    Objectives To assess the evidence for the existence and prevalence of sleep attacks in patients taking dopamine agonists for Parkinson's disease, the type of drugs implicated, and strategies for prevention and treatment. Design Review of publications between July 1999 and May 2001 in which sleep attacks or narcoleptic-like attacks were discussed in patients with Parkinson's disease. Results 124 patients with sleep events were found in 20 publications. Overall, 6.6% of patients taking dopamine agonists who attended movement disorder centres had sleep events. Men were over-represented. Sleep events occurred at both high and low doses of the drugs, with different durations of treatment (0-20 years), and with or without preceding signs of tiredness. Sleep attacks are a class effect, having been found in patients taking the following dopamine agonists: levodopa (monotherapy in 8 patients), ergot agonists (apomorphine in 2 patients, bromocriptine in 13, cabergoline in 1, lisuride or piribedil in 23, pergolide in 5,) and non-ergot agonists (pramipexole in 32, ropinirole in 38). Reports suggest two distinct types of events: those of sudden onset without warning and those of slow onset with prodrome drowsiness. Conclusion Insufficient data are available to provide effective guidelines for prevention and treatment of sleep events in patients taking dopamine agonists for Parkinson's disease. Prospective population based studies are needed to provide this information. What is already known on this topicCar crashes in patients with Parkinson's disease have been associated with sleep attacks caused by the dopamine agonists pramipexole and ropiniroleWhether sleep attacks exist, their connection with certain agonists, prevention or treatment, and the justification of legal actions are controversialWhat this study addsSleep attacks as a phenomenon distinct from normal somnolence really do existThey are a class effect of all dopamine drugsEffective prevention and treatment

  19. Identification of M-CSF agonists and antagonists

    DOEpatents

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  20. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    PubMed

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. PMID:25326839

  1. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    PubMed

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. PMID:25437461

  2. PPAR dual agonists: are they opening Pandora's Box?

    PubMed

    Balakumar, Pitchai; Rose, Madhankumar; Ganti, Subrahmanya S; Krishan, Pawan; Singh, Manjeet

    2007-08-01

    Cardiovascular disorders are the major cause of mortality in patients of diabetes mellitus. Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of three subtypes such as PPARalpha, PPARgamma and PPARdelta/beta. Activation of PPARalpha reduces triglycerides and involves in regulation of energy homeostasis. Activation of PPARgamma causes insulin sensitization and enhances glucose metabolism, whereas activation of PPARdelta enhances fatty acid metabolism. Current therapeutic strategies available for the treatment of diabetes do not inhibit the associated secondary cardiovascular complications. Hence, the development of multimodal drugs which can reduce hyperglycemia and concomitantly inhibit the progression of secondary cardiovascular complications may offer valuable therapeutic option. Several basic and clinical studies have exemplified the beneficial effects of PPARalpha and PPARgamma ligands in preventing the cardiovascular risks. The PPARalpha/gamma dual agonists are developed to increase insulin sensitivity and simultaneously prevent diabetic cardiovascular complications. Such compounds are under clinical trials and proposed for treatment of Type II diabetes with secondary cardiovascular complications. However, PPARalpha/gamma dual agonists such as muraglitazar, tesaglitazar and ragaglitazar have been noted to produce several cardiovascular risks and carcinogenicity, which raised number of questions about the clinical applications of dual agonists in diabetes and its associated complications. The ongoing basic studies have elucidated the cardio protective role of PPARdelta. Therefore, further studies are on the track to develop PPARalpha/delta and PPAR gamma/delta dual agonists and PPARalpha/gamma/delta pan agonists for the treatment of diabetic cardiovascular complications. The present review critically analyzes the protective and detrimental effect of PPAR agonists in

  3. Mechanisms of inverse agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Strange, Philip G

    2005-05-01

    Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been examined. Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. K(i) values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. K(coupled) and K(uncoupled) were statistically different for the set of compounds tested (ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. These observations were supported by simulations of these competition experiments according to the extended ternary complex model. Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [35S]GTP gamma S binding to varying degrees in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (-)-sulpiride was unaffected. These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism. PMID:15735658

  4. Confinement from constant field condensates

    NASA Astrophysics Data System (ADS)

    Gaete, Patricio; Guendelman, Eduardo; Spallucci, Euro

    2007-01-01

    For (2 + 1)- and (3 + 1)-dimensional reformulated SU (2) Yang-Mills theory, we compute the interaction potential within the framework of the gauge-invariant but path-dependent variables formalism. This reformulation is due to the presence of a constant gauge field condensate. Our results show that the interaction energy contains a linear term leading to the confinement of static probe charges. This result is equivalent to that of the massive Schwinger model.

  5. An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

    PubMed Central

    Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

    2016-01-01

    Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (INMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated INMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on INMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated INMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of INMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

  6. An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons.

    PubMed

    Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

    2016-01-01

    Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca(2+)-activated K(+) (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5'-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

  7. Determination of stability constants of aminoglycoside antibiotics with their metal complexes

    NASA Astrophysics Data System (ADS)

    Tiwow, Vanny M. A.

    2014-03-01

    One group of aminoglycoside antibiotics contains aminosugars. The aminosugar neomycin B with its derivate product neamine (2-Deoxy-4-0-(2,6-diamino-2,6-dideoxy-α-D-glucopyranosyl)-D-Streptamine) was identified as a free ligands and metal complexes. In particular, the stability constants of metal complexes by potentiometric titration techniques were investigated. Our previous study had determined the acid dissociation constants of these aminosugars with few metal complexes in fair depth. In this work, the complexation of two pyridine-containing amino alcohols and an amino sugar (neamine) have been measured potentiometrically. For instance, the stability constant of copper(II) complexation were determine and the model system generated an excellent fit. Stability constants with several metals have been determined and will be reported.

  8. Differential effects of AMPK agonists on cell growth and metabolism

    PubMed Central

    Vincent, Emma E.; Coelho, Paula P.; Blagih, Julianna; Griss, Takla; Viollet, Benoit; Jones, Russell G.

    2016-01-01

    As a sensor of cellular energy status, the AMP-activated protein kinase (AMPK) is believed to act in opposition to the metabolic phenotypes favored by proliferating tumor cells. Consequently, compounds known to activate AMPK have been proposed as cancer therapeutics. However, the extent to which the anti-neoplastic properties of these agonists are mediated by AMPK is unclear. Here we examined the AMPK-dependence of six commonly used AMPK agonists (metformin, phenformin, AICAR, 2DG, salicylate and A-769662) and their influence on cellular processes often deregulated in tumor cells. We demonstrate that the majority of these agonists display AMPK-independent effects on cell proliferation and metabolism with only the synthetic activator, A-769662, exerting AMPK-dependent effects on these processes. We find that A-769662 promotes an AMPK-dependent increase in mitochondrial spare respiratory capacity (SRC). Finally, contrary to the view of AMPK activity being tumor suppressive, we find A-769662 confers a selective proliferative advantage to tumor cells growing under nutrient deprivation. Our results indicate that many of the anti-growth properties of these agonists cannot be attributed to AMPK activity in cells, and thus any observed effects using these agonists should be confirmed using AMPK-deficient cells. Ultimately, our data urge caution, not only regarding the type of AMPK agonist proposed for cancer treatment, but also the context in which they are used. PMID:25241895

  9. Chemical Modification of the M1 Agonist VU0364572 Reveals Molecular Switches in Pharmacology and a Bitopic Binding Mode

    PubMed Central

    2012-01-01

    We previously reported the discovery of VU0364572 and VU0357017 as M1-selective agonists that appear to activate M1 through actions at an allosteric site. Previous studies have revealed that chemical scaffolds for many allosteric modulators contain molecular switches that allow discovery of allosteric antagonists and allosteric agonists or positive allosteric modulators (PAMs) based on a single chemical scaffold. Based on this, we initiated a series of studies to develop selective M1 allosteric antagonists based on the VU0364572 scaffold. Interestingly, two lead antagonists identified in this series, VU0409774 and VU0409775, inhibited ACh-induced Ca2+ responses at rat M1–5 receptor subtypes, suggesting they are nonselective muscarinic antagonists. VU0409774 and VU0409775 also completely displaced binding of the nonselective radioligand [3H]-NMS at M1 and M3 mAChRs with affinities similar to their functional IC50 values. Finally, Schild analysis revealed that these compounds inhibit M1 responses through a fully competitive interaction at the orthosteric binding site. This surprising finding prompted further studies to determine whether agonist activity of VU0364572 and VU0357017 may also engage in previously unappreciated actions at the orthosteric site on M1. Surprisingly, both VU0364572 and VU0357017 completely displaced [3H]-NMS binding to the orthosteric site of M1–M5 receptors at high concentrations. Furthermore, evaluation of agonist activity in systems with varying levels of receptor reserve and Furchgott analysis using a cell line expressing M1 under control of an inducible promotor was consistent with an action of these compounds as weak orthosteric partial agonists of M1. However, consistent with previous studies suggesting actions at a site that is distinct from the orthosteric binding site, VU0364572 or VU0357017 slowed the rate of [3H]-NMS dissociation from CHO-rM1 membranes. Together, these results suggest that VU0364572 and VU0357017 act as

  10. Dissociative electron attachment studies on acetone

    SciTech Connect

    Prabhudesai, Vaibhav S. Tadsare, Vishvesh; Ghosh, Sanat; Gope, Krishnendu; Davis, Daly; Krishnakumar, E.

    2014-10-28

    Dissociative electron attachment (DEA) to acetone is studied in terms of the absolute cross section for various fragment channels in the electron energy range of 0–20 eV. H{sup −} is found to be the most dominant fragment followed by O{sup −} and OH{sup −} with only one resonance peak between 8 and 9 eV. The DEA dynamics is studied by measuring the angular distribution and kinetic energy distribution of fragment anions using Velocity Slice Imaging technique. The kinetic energy and angular distribution of H{sup −} and O{sup −} fragments suggest a many body break-up for the lone resonance observed. The ab initio calculations show that electron is captured in the multi-centered anti-bonding molecular orbital which would lead to a many body break-up of the resonance.

  11. Molecular Dissociation Induced by Electron Collisions

    NASA Astrophysics Data System (ADS)

    Wolf, Andreas

    2009-05-01

    Free electrons can efficiently break molecules or molecular ions in low-energy collisions by the processes of dissociative recombination or attachment. These processes make slow electrons efficient chemical agents in many environments. For dissociative recombination, in particular, studies of the underlying reaction paths and mechanisms have become possible on a uniquely elementary level in recent years both for theory and experiment. On the experimental side, collisions can be prepared at resolved collision energies down to the meV (10 Kelvin) level, increasingly gaining control also over the initial molecular quantum level, and individual events are detected and kinematically analyzed by fast-beam coincidence fragment imaging. Experiments are reported from the ion cooler ring TSR in Heidelberg. Stored beams of molecular ions cooled in their external and internal degrees of freedom are collinearly merged with intense and cold electron beams from cryogenic GaAs photocathodes, recently shown to yield fast cooling of the center-of-mass motion also for heavy and correspondingly slow molecular ion beams. To reconstruct the molecular fragmentation events multiparticle imaging can now be used systematically with collision energies set a wide range, especially aiming at specific electron capture resonances. Thus, for CF^+ it is found that the electronic state of the C fragment (^3P or ^1D) switches resonantly when the collision energy is changed by only a small fraction. As a new powerful tool, an energy-sensitive multi-strip surface-barrier detector (EMU) has been set up to measure with near-unity efficiency the masses of all fragments together with their hit positions in high-multiplicity events. Among many uses, this device allows internal molecular excitations to be derived for individual chemical channels in polyatomic fragmentation. New results will be presented in particular on the breakup of the hydronium ion (D3O^+).

  12. Perception of specific trigeminal chemosensory agonists

    PubMed Central

    Frasnelli, J; Albrecht, J; Bryant, B; Lundström, JN

    2011-01-01

    The intranasal trigeminal system is a third chemical sense in addition to olfaction and gustation. As opposed to smell and taste, we still lack knowledge on the relationship between receptor binding and perception for the trigeminal system. We therefore investigated the sensitivity of the intranasal trigeminal system towards agonists of the trigeminal receptors TRPM8 and TRPA1 by assessing subjects’ ability to identify which nostril has been stimulated in a monorhinal stimulation design. We summed the number of correct identifications resulting in a lateralization score. Stimuli were menthol (activating TRPM8 receptors), eucalyptol (TRPM8), mustard oil (TRPA1) and two mixtures thereof (menthol/eucalyptol and menthol/mustard oil). In addition, we examined the relationship between intensity and lateralization scores and investigated whether intensity evaluation and lateralization scores of the mixtures show additive effects. All stimuli were correctly lateralized significantly above chance. Across subjects the lateralization scores for single compounds activating the same receptor showed a stronger correlation than stimuli activating different receptors. Although single compounds were isointense, the mixture of menthol and eucalyptol (activating only TRPM8) was perceived as weaker and was lateralized less accurately than the mixture of menthol and mustard oil (activating both TRPM8 and TRPA1) suggesting suppression effects in the former mixture. In conclusion, sensitivity of different subpopulations of trigeminal sensory neurons seems to be related, but only to a certain degree. The large coherence in sensitivity between various intranasal trigeminal stimuli suggests that measuring sensitivity to one single trigeminal chemical stimulus may be sufficient to generally assess the trigeminal system’s chemosensitivity. Further, for stimuli activating the same receptor a mixture suppression effect appears to occur similar to that observed in the other chemosensory

  13. Memory Abilities in Williams Syndrome: Dissociation or Developmental Delay Hypothesis?

    ERIC Educational Resources Information Center

    Sampaio, Adriana; Sousa, Nuno; Fernandez, Montse; Henriques, Margarida; Goncalves, Oscar F.

    2008-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder often described as being characterized by a dissociative cognitive architecture, in which profound impairments of visuo-spatial cognition contrast with relative preservation of linguistic, face recognition and auditory short-memory abilities. This asymmetric and dissociative cognition…

  14. Dissociative Spectrum Disorders in the Primary Care Setting.

    PubMed

    Elmore, James L.

    2000-04-01

    Dissociative disorders have a lifetime prevalence of about 10%. Dissociative symptoms may occur in acute stress disorder, posttraumatic stress disorder, somatization disorder, substance abuse, trance and possession trance, Ganser's syndrome, and dissociative identity disorder, as well as in mood disorders, psychoses, and personality disorders. Dissociative symptoms and disorders are observed frequently among patients attending our rural South Carolina community mental health center. Given the prevalence of mental illness in primary care settings and the diagnostic difficulties encountered with dissociative disorders, such illness may be undiagnosed or misdiagnosed in primary care settings. We developed an intervention model that may be applicable to primary care settings or helpful to primary care physicians. Key points of the intervention are identification of dissociative symptoms, patient and family education, review of the origin of the symptoms as a method of coping with trauma, and supportive reinforcement of cognitive and relaxation skills during follow-up visits. Symptom recognition, Education of the family, Learning new skills, and Follow-up may be remembered by the mnemonic device SELF. We present several cases to illustrate dissociative symptoms and our intervention. Physicians and other professionals using the 4 steps and behavioral approaches will be able to better recognize and triage patients with dissociative symptoms. Behaviors previously thought to be secondary to psychosis or personality disorders may be seen in a new frame of reference, strengthening the therapeutic alliance while reducing distress and acting-out behaviors. PMID:15014580

  15. Coherent dissociation of relativistic {sup 9}C nuclei

    SciTech Connect

    Krivenkov, D. O.; Artemenkov, D. A.; Bradnova, V.; Vokal, S.; Zarubin, P. I. Zarubina, I. G.; Kondratieva, N. V.; Malakhov, A. I.; Moiseenko, A. A.; Orlova, G. I.; Peresadko, N. G.; Polukhina, N. G.; Rukoyatkin, P. A.; Rusakova, V. V.; Sarkisyan, V. R.; Stanoeva, R.; Haiduc, M.; Kharlamov, S. P.

    2010-12-15

    Results on the coherent dissociation of relativistic {sup 9}C nuclei in a nuclear track emulsion are described. These results include the charge topology and kinematical features of final states. Events of {sup 9}C {yields} 3{sup 3}He coherent dissociation are identified.

  16. Errors of Logic and Scholarship Concerning Dissociative Identity Disorder

    ERIC Educational Resources Information Center

    Ross, Colin A.

    2009-01-01

    The author reviewed a two-part critique of dissociative identity disorder published in the "Canadian Journal of Psychiatry". The two papers contain errors of logic and scholarship. Contrary to the conclusions in the critique, dissociative identity disorder has established diagnostic reliability and concurrent validity, the trauma histories of…

  17. The rise and fall of dissociative identity disorder.

    PubMed

    Paris, Joel

    2012-12-01

    Dissociative identity disorder (DID), once considered rare, was frequently diagnosed during the 1980s and 1990s, after which interest declined. This is the trajectory of a medical fad. DID was based on poorly conceived theories and used potentially damaging treatment methods. The problem continues, given that the DSM-5 includes DID and accords dissociative disorders a separate chapter in its manual. PMID:23197123

  18. Dissociative Spectrum Disorders in the Primary Care Setting

    PubMed Central

    Elmore, James L.

    2000-01-01

    Dissociative disorders have a lifetime prevalence of about 10%. Dissociative symptoms may occur in acute stress disorder, posttraumatic stress disorder, somatization disorder, substance abuse, trance and possession trance, Ganser's syndrome, and dissociative identity disorder, as well as in mood disorders, psychoses, and personality disorders. Dissociative symptoms and disorders are observed frequently among patients attending our rural South Carolina community mental health center. Given the prevalence of mental illness in primary care settings and the diagnostic difficulties encountered with dissociative disorders, such illness may be undiagnosed or misdiagnosed in primary care settings. We developed an intervention model that may be applicable to primary care settings or helpful to primary care physicians. Key points of the intervention are identification of dissociative symptoms, patient and family education, review of the origin of the symptoms as a method of coping with trauma, and supportive reinforcement of cognitive and relaxation skills during follow-up visits. Symptom recognition, Education of the family, Learning new skills, and Follow-up may be remembered by the mnemonic device SELF. We present several cases to illustrate dissociative symptoms and our intervention. Physicians and other professionals using the 4 steps and behavioral approaches will be able to better recognize and triage patients with dissociative symptoms. Behaviors previously thought to be secondary to psychosis or personality disorders may be seen in a new frame of reference, strengthening the therapeutic alliance while reducing distress and acting-out behaviors. PMID:15014580

  19. Dissociative Disorders in Children: Behavioral Profiles and Problems.

    ERIC Educational Resources Information Center

    Putnam, Frank W.

    1993-01-01

    Clinical research has established a connection between childhood trauma and the development of dissociative disorders in adults. Pathological dissociation produces a range of symptoms and behaviors such as amnesias, rapid shifts in mood and behavior, and auditory and visual hallucinations. Many of these symptoms are misdiagnosed as attention,…

  20. Early Indicators of Pathological Dissociation in Sexually Abused Children.

    ERIC Educational Resources Information Center

    McElroy, Linda Provus

    1992-01-01

    This paper reviews factors in the professional neglect of multiple personality disorder (MPD) and sexual abuse in childhood, as well as recent diagnostic developments in childhood dissociative disorders. The identification of subtle dissociative symptomatology in children is illustrated, and two case examples are presented. (Author)

  1. Modeling the electron-impact dissociation of methane

    NASA Astrophysics Data System (ADS)

    Ziółkowski, Marcin; Vikár, Anna; Mayes, Maricris Lodriguito; Bencsura, Ákos; Lendvay, György; Schatz, George C.

    2012-12-01

    The product yield of the electron-impact dissociation of methane has been studied with a combination of three theoretical methods: R-matrix theory to determine the electronically inelastic collisional excitation cross sections, high-level electronic structure methods to determine excited states energies and derivative couplings, and trajectory surface hopping (TSH) calculations to determine branching in the dissociation of the methane excited states to give CH3, CH2, and CH. The calculations involve the lowest 24 excited-state potential surfaces of methane, up to the ionization energy. According to the R-matrix calculations, electron impact preferentially produces triplet excited states, especially for electron kinetic energies close to the dissociation threshold. The potential surfaces of excited states are characterized by numerous avoided and real crossings such that the TSH calculations show rapid cascading down to the lowest excited singlet or triplet states, and then slower the dissociation of these lowest states. Product branching for electron-impact dissociation was therefore estimated by combining the electron-impact excitation cross sections with TSH product branching ratios that were obtained from the lowest singlet and triplet states, with the singlet dissociation giving a comparable formation of CH2 and CH3 while triplet dissociation gives CH3 exclusively. The overall branching in electron-impact dissociation is dominated by CH3 over CH2. A small branching yield for CH is also predicted.

  2. Switch Function and Pathological Dissociation in Acute Psychiatric Inpatients

    PubMed Central

    Chiu, Chui-De; Tseng, Mei-Chih Meg; Chien, Yi-Ling; Liao, Shih-Cheng; Liu, Chih-Min; Yeh, Yei-Yu; Hwu, Hai-Gwo

    2016-01-01

    Swift switching, along with atypical ability on updating and inhibition, has been found in non-clinical dissociators. However, whether swift switching is a cognitive endophenotype that intertwines with traumatisation and pathological dissociation remains unknown. Unspecified acute psychiatric patients were recruited to verify a hypothesis that pathological dissociation is associated with swift switching and traumatisation may explain this relationship. Behavioural measures of intellectual function and three executive functions including updating, switching and inhibition were administered, together with standardised scales to evaluate pathological dissociation and traumatisation. Our results showed superior control ability on switching and updating in inpatients who displayed more symptoms of pathological dissociation. When all three executive functions were entered as predictors, in addition to intellectual quotient and demographic variables to regress upon pathological dissociation, switching rather than updating remained the significant predictor. Importantly, the relationship between pathological dissociation and switching became non-significant when the effect of childhood trauma were controlled. The results support a trauma-related switching hypothesis which postulates swift switching as a cognitive endophenotype of pathological dissociation; traumatisation in childhood may explain the importance of swift switching. PMID:27123578

  3. RAIRS observation of photoinduced dissociation of NO on Ni(111)

    NASA Astrophysics Data System (ADS)

    Magkoev, Tamerlan T.; Song, Moon-Bong; Fukutani, Katsuyuki; Murata, Yoshitada

    1995-06-01

    The properties of the {NO}/{Ni(111) } system under nanosecond ultraviolet laser light irradiation are studied by reflection absorption infrared spectroscopy. It is found that adsorbed NO molecules are dissociated by laser light. Dissociation proceeds effectively in a dilute NO layer, whereas it is suppressed in a saturated overlayer.

  4. Self-Destructive Behavior in People with Dissociative Disorders.

    ERIC Educational Resources Information Center

    Saxe, Glenn N.; Chawla, Neharika; Van der Kolk, Bessel

    2002-01-01

    Study assesses self-destructive behavior in a group of inpatients who have dissociative disorders compared to those who report few dissociative symptoms. Results reveal that these patients more frequently engage in self-destructive behaviors, use more methods of self-injury, and begin to injure themselves at an earlier age then patients who do not…

  5. Identification of Determinants Required for Agonistic and Inverse Agonistic Ligand Properties at the ADP Receptor P2Y12

    PubMed Central

    Schmidt, Philipp; Ritscher, Lars; Dong, Elizabeth N.; Hermsdorf, Thomas; Cöster, Maxi; Wittkopf, Doreen; Meiler, Jens

    2013-01-01

    The ADP receptor P2Y12 belongs to the superfamily of G protein–coupled receptors (GPCRs), and its activation triggers platelet aggregation. Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events. P2Y12 displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists. Only a few inverse agonists of P2Y12 have been described. To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y12 and 28 constitutively active mutants. Results showed that ATP and ATP derivatives are agonists at P2Y12. The potency at P2Y12 was 2-(methylthio)-ADP > 2-(methylthio)-ATP > ADP > ATP. Determinants required for agonistic ligand activity were identified. Molecular docking studies revealed a binding pocket for the ATP derivatives that is bordered by transmembrane helices 3, 5, 6, and 7 in human P2Y12, with Y105, E188, R256, Y259, and K280 playing a particularly important role in ligand interaction. N-Methyl-anthraniloyl modification at the 3′-OH of the 2′-deoxyribose leads to ligands (mant-deoxy-ATP [dATP], mant-deoxy-ADP) with inverse agonist activity. Inverse agonist activity of mant-dATP was found at the WT human P2Y12 and half of the constitutive active P2Y12 mutants. This study showed that, in addition to ADP and ATP, other ATP derivatives are not only ligands of P2Y12 but also agonists. Modification of the ribose within ATP can result in inverse activity of ATP-derived ligands. PMID:23093496

  6. Peritraumatic dissociation after loss: latent structure and associations with psychopathology.

    PubMed

    Boelen, Paul A; Keijsers, Loes; van den Hout, Marcel A

    2012-04-01

    This study investigated the factor-structure of retrospectively assessed peritraumatic dissociation in the moments surrounding the death of a loved one and concurrent and prospective associations of such peritraumatic dissociation with loss-related emotional distress. Data were available from 168 people, bereaved in the preceding year. They completed the Peritraumatic Dissociative Experiences Questionnaire with their loss as the index event, together with measures of prolonged grief disorder, depression, and posttraumatic stress disorder; 117 completed symptom measures again 1 year later. Confirmatory factor analysis comparing the fit of four competing models showed that the eight-item one-factor model found in the first study using the Peritraumatic Dissociative Experiences Questionnaire provided the best fit to the data. Peritraumatic dissociation predicted concurrent and prospective symptom levels even when controlling for neuroticism and demographic and loss-related variables. PMID:22456592

  7. Controllable dissociations of PH3 molecules on Si(001)

    NASA Astrophysics Data System (ADS)

    Liu, Qin; Lei, Yanhua; Shao, Xiji; Ming, Fangfei; Xu, Hu; Wang, Kedong; Xiao, Xudong

    2016-04-01

    We demonstrate for the first time to our knowledge that controllable dissociation of PH3 adsorption products PH x (x = 2, 1) can be realized by STM (scanning tunneling microscope) manipulation techniques at room temperature. Five dissociative products and their geometric structures are identified via combining STM experiments and first-principle calculations and simulations. In total we realize nine kinds of controllable dissociations by applying a voltage pulse among the PH3-related structures on Si(001). The dissociation rates of the five most common reactions are measured by the I-t spectrum method as a function of voltage. The suddenly increased dissociation rate at 3.3 V indicates a transition from multivibrational excitation to single-step excitation induced by inelastic tunneling electrons. Our studies prove that selectively breaking the chemical bonds of a single molecule on semiconductor surface by STM manipulation technique is feasible.

  8. Dissociation of methane hydrate in aqueous NaCl solutions.

    PubMed

    Yagasaki, Takuma; Matsumoto, Masakazu; Andoh, Yoshimichi; Okazaki, Susumu; Tanaka, Hideki

    2014-10-01

    Molecular dynamics simulations of the dissociation of methane hydrate in aqueous NaCl solutions are performed. It is shown that the dissociation of the hydrate is accelerated by the formation of methane bubbles both in NaCl solutions and in pure water. We find two significant effects on the kinetics of the hydrate dissociation by NaCl. One is slowing down in an early stage before bubble formation, and another is swift bubble formation that enhances the dissociation. These effects arise from the low solubility of methane in NaCl solution, which gives rise to a nonuniform spatial distribution of solvated methane in the aqueous phase. We also demonstrate that bubbles form near the hydrate interface in dense NaCl solutions and that the hydrate dissociation proceeds inhomogeneously due to the bubbles. PMID:25237735

  9. Dissociative Symptoms and Mother's Marital Status in Young Adult Population

    PubMed Central

    Bob, Petr; Selesova, Petra; Raboch, Jiri; Kukla, Lubomir

    2015-01-01

    Abstract Current findings suggest that mother's marital status indicating father's absence or conflicting relationship to father may be specifically related to dissociation and other stress-related symptoms. We have assessed relationships of mother's marital status, dissociative symptoms, and other psychopathological manifestations in a sample of 19 years’ old young adults (N = 364) participating in European longitudinal study (European Longitudinal Study of Parenthood and Childhood). The results show clinically significant manifestations of dissociative symptoms in young adult men whose mothers were fatherless and in women whose mothers were re-married. Other psychopathological symptoms did not reach clinically significant manifestations. The results suggest that significant factor related to high level of dissociative symptoms in men growing in fatherless families might be linked with disturbed and conflicting attachment to a father's figure and pathological dependent attachment to mother. In women dissociative symptoms likely are linked to conflicting relationship between mother and daughter associated with stepfather’ presence in the family. PMID:25590849

  10. Controllable dissociations of PH3 molecules on Si(001).

    PubMed

    Liu, Qin; Lei, Yanhua; Shao, Xiji; Ming, Fangfei; Xu, Hu; Wang, Kedong; Xiao, Xudong

    2016-04-01

    We demonstrate for the first time to our knowledge that controllable dissociation of PH3 adsorption products PHx (x = 2, 1) can be realized by STM (scanning tunneling microscope) manipulation techniques at room temperature. Five dissociative products and their geometric structures are identified via combining STM experiments and first-principle calculations and simulations. In total we realize nine kinds of controllable dissociations by applying a voltage pulse among the PH3-related structures on Si(001). The dissociation rates of the five most common reactions are measured by the I-t spectrum method as a function of voltage. The suddenly increased dissociation rate at 3.3 V indicates a transition from multivibrational excitation to single-step excitation induced by inelastic tunneling electrons. Our studies prove that selectively breaking the chemical bonds of a single molecule on semiconductor surface by STM manipulation technique is feasible. PMID:26894452

  11. Promotion of Methane Hydrate Dissociation by Underwater Ultrasonic Wave

    NASA Astrophysics Data System (ADS)

    Miura, Hikaru; Takata, Makoto; Tajima, Daisuke; Tsuyuki, Kenichirou

    2006-05-01

    The methane hydrate that exists in the abyssal floor is receiving attention as a nonconventional type of natural gas resource. An efficient dissociation technology is necessary and indispensable to achieve a steady supply of methane from methane hydrate because it does not easily dissociate in a stable environment of high pressure and low temperature. We consider that underwater ultrasonic wave irradiation may be a method of promoting the dissociation of methane hydrate on the basis of the facilitator effect. We carried out a preliminary examination using dry ice at various pressures, water temperatures, and input electric power. Methane hydrate was similarly examined. As a result, it was clarified that the dissociation time was shorted by the ultrasonic wave, and the wave was effective when the water temperature was low at the time of dissociation.

  12. Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2014-01-01

    Unresolved mourning is marked by disorganized behavior and states of mind. In this study, we speculated that pathological dissociation would mediate the effects of unresolved mourning on supernatural beliefs. This hypothesis was determined based on findings that indicate an association between higher levels of dissociation, stronger beliefs in the supernatural and unresolved mourning. We examined two groups of participants, one classified as non-unresolved (non-U) (n = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma as measured by the Adult Attachment Interview (AAI). Two self-report instruments were administered to measure supernatural beliefs and dissociation. As hypothesized, the multivariate analysis of variance indicated mean differences between the two groups. The unresolved group had greater belief in the supernatural and more pathological dissociative processes. The mediation analysis demonstrated that pathological dissociation fully mediated the effects of unresolved mourning on supernatural beliefs. PMID:24913392

  13. Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications.

    PubMed

    Saidak, Zuzana; Brazier, Michel; Kamel, Saïd; Mentaverri, Romuald

    2009-12-01

    The calcium-sensing receptor (CaR) belongs to the G protein-coupled receptor superfamily, with a characteristic structure consisting of seven transmembrane helices, an intracellular C-terminal and an extracellular N terminal domain. The primary physiological function of the CaR is the maintenance of constant blood Ca2+ levels, as a result of its ability to sense very small changes in extracellular Ca2+ (Ca2+(o)). Nevertheless, in addition to being expressed in tissues involved in Ca2+(o) homeostasis, the CaR is also expressed in tissues not involved in mineral homeostasis, suggestive of additional physiological functions. Numerous agonists and modulators of the CaR are now known in addition to Ca2+(o), including various divalent and trivalent cations, aromatic l-amino acids, polyamines, and aminoglycoside antibiotics. The signaling of the CaR is also regulated by extracellular pH and ionic strength. The activated CaR couples mainly to the phospholipase Cbeta and extracellular signal-regulated kinase 1/2 signaling pathways, and it decreases intracellular cAMP levels, leading to various physiological effects. The recent identification of synthetic allosteric modulators of the CaR has opened up a new field of research possibilities. Calcimimetics and calcilytics, which increase and decrease agonist signaling via the CaR, respectively, may facilitate the manipulation of the CaR and thus aid in further investigations of its precise signaling. These allosteric modulators, as well as strontium, have been demonstrated to have therapeutic potential for the treatment of disorders involving the CaR. This review discusses the various agonists and modulators of the CaR, differences in their binding and signaling, and their roles as therapeutics in various diseases. PMID:19779033

  14. Noribogaine is a G-protein biased κ-opioid receptor agonist.

    PubMed

    Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

    2015-12-01

    Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders. PMID:26302653

  15. Influence of the dopamine receptor agonists fenoldopam and quinpirole in the rat superior mesenteric vascular bed.

    PubMed Central

    Dupont, A. G.; Lefebvre, R. A.; Vanderniepen, P.

    1987-01-01

    The effect of local administration of the dopamine 2 (DA2)-receptor agonist quinpirole and of the DA1-receptor agonist fenoldopam was studied in the in situ, constant flow autoperfused, superior mesenteric vascular bed of the rat. Local infusion of quinpirole (30 micrograms kg-1 min-1 for 5 min) had no effect on baseline perfusion pressure; it reduced the pressor responses to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial sympathetic nerves to 45.6 +/- 2.1% of its original value but did not modify similar pressor responses produced by locally administered noradrenaline. The inhibitory effect of quinpirole was antagonized by the selective DA2-receptor antagonist domperidone (10 micrograms kg-1) but not by the selective DA1-receptor antagonist SCH 23390 (50 micrograms kg-1). Local infusion of fenoldopam (30 micrograms kg-1 min-1 for 5 min) reduced baseline perfusion pressure to 89.9 +/- 1.9%, increased the pressor response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial nerves to 134.7 +/- 14.0%, but reduced the pressor response to locally administered noradrenaline to 37.2 +/- 8.2%. Similar pressor responses induced by the selective alpha 1-adrenoceptor agonist phenylephrine were also reduced by fenoldopam (to 38.4 +/- 6.4%), but responses to locally administered angiotensin II were not modified. Pretreatment with SCH 23390 (50 micrograms kg-1) antagonized the effect of fenoldopam on baseline perfusion pressure, but had no influence on the effect of fenoldopam on responses to electrical stimulation or to noradrenaline. Pretreatment with the selective alpha 2-adrenoceptor antagonist rauwolscine (100 micrograms kg-1) had no effect on the reduction in baseline perfusion pressure induced by fenoldopam nor on its inhibitory effect on the response to noradrenaline, but it antagonized the stimulatory effect of fenoldopam on the response to electrical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2886174

  16. PREFACE: Eighth International Conference on Dissociative Recombination (DR2010)

    NASA Astrophysics Data System (ADS)

    Guberman, Steven L.; Orel, Ann E.

    2011-07-01

    In dissociative recombination (DR), a molecular ion captures an electron and falls apart. One might initially conclude that this process is relatively simple. However, a review of the DR literature over the past 60 years, since the pioneering papers of Sir David Bates [1], shows that the study of DR has proved to be highly challenging for both theorists and experimentalists. Both this challenge and the ubiquitous importance of the process have made its study rewarding, endlessly interesting, and full of surprises. DR is fundamentally the interaction of an electronic continuum with a vibrational continuum often connected by quasibound intermediate states. Autoionization in the first continuum competes with dissociation in the second. DR occurs at the total energy of an ion plus a free electron and is in the same region as vibrationally excited Rydberg states and other neutral superexcited states. All these states interact with each other prior to dissociation, forming a complex that controls the quantum yields of products. The complexity of the process has required both innovation and ingenuity on the part of both theorists and experimentalists. Over the years, it has become apparent that in order to compare theoretical and experimental results, the experiments must identify the electronic, vibrational and for low mass ions, the rotational state. The traditional disagreement between theoretical and experimental results has been due, in part, to the sensitivity of DR cross sections and rate constants to the state of the recombining ion. Great progress has been made in recent years in both flowing afterglow and storage ring experiments aimed at reducing this uncertainty. The latest advances and insights in theory and experiment were the topics of the Eighth International Conference on Dissociative Recombination held at the Granlibakken Lodge at Lake, Tahoe, California, 16-20 August 2010. The conference was part of a series of conferences on DR that started at Chateau

  17. Constants of acid‒base equilibria in an aqueous amikacin aminoglycoside solution at 298 K

    NASA Astrophysics Data System (ADS)

    Alekseev, V. G.; Markova, E. V.

    2016-03-01

    The acid dissociation constants of form p K 1 = 7.34 ± 0.01, p K 2 = 7.84 ± 0.01, p K 3 = 8.77 ± 0.01, p K 4 = 9.49 ± 0.01, and p K 5 = 10.70 ± 0.02 of cationic amikacin are determined by pH-metric titration at 25°C against the background of 0.1 mol/L KNO3. K 1, K 2, K 3, and K 4 correspond to the dissociation of protons coordinated to amino groups, while K 5 characterizes the dissociation of the hydroxyl hydrogen atom, testifying to the amphoteric character of amikacin molecules. Applying density functional theory (DFT) with the B3LYP hybrid functional and the 6-311G**++ basis set, the partial charges on the atoms of an amikacin molecule are calculated. It is concluded that the dissociation of H(55)hydrogen atom occurs with a greatest partial charge of +0.53631.

  18. Henry's law constants of polyols

    NASA Astrophysics Data System (ADS)

    Compernolle, S.; Müller, J.-F.

    2014-05-01

    Henry's law constants (HLC) are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. Depending on the case, infinite dilution activity coefficients (IDACs), solid state pressures or activity coefficient ratios are obtained as intermediary results. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014), an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.

  19. Markov constant and quantum instabilities

    NASA Astrophysics Data System (ADS)

    Pelantová, Edita; Starosta, Štěpán; Znojil, Miloslav

    2016-04-01

    For a qualitative analysis of spectra of certain two-dimensional rectangular-well quantum systems several rigorous methods of number theory are shown productive and useful. These methods (and, in particular, a generalization of the concept of Markov constant known in Diophantine approximation theory) are shown to provide a new mathematical insight in the phenomenologically relevant occurrence of anomalies in the spectra. Our results may inspire methodical innovations ranging from the description of the stability properties of metamaterials and of certain hiddenly unitary quantum evolution models up to the clarification of the mechanisms of occurrence of ghosts in quantum cosmology.

  20. The constant-V vortex

    NASA Astrophysics Data System (ADS)

    Faller, Alan J.

    2001-05-01

    It has been found that the generation of swirl by a continuous rotary oscillation of a right-circular cylinder partially filled with water can leave a vortex with a radially constant tangential velocity, V, i.e. [partial partial differential]V/[partial partial differential]r = 0, excepting a small central core and the sidewall boundary layer. This vortex maintains [partial partial differential]V/[partial partial differential]r = 0 during viscous decay by the turbulent bottom boundary layer, a fact that suggests that [partial partial differential]V/[partial partial differential]r = 0 is a stable condition for a decaying vortex.

  1. Assessing uncertainty in physical constants

    NASA Astrophysics Data System (ADS)

    Henrion, Max; Fischhoff, Baruch

    1986-09-01

    Assessing the uncertainty due to possible systematic errors in a physical measurement unavoidably involves an element of subjective judgment. Examination of historical measurements and recommended values for the fundamental physical constants shows that the reported uncertainties have a consistent bias towards underestimating the actual errors. These findings are comparable to findings of persistent overconfidence in psychological research on the assessment of subjective probability distributions. Awareness of these biases could help in interpreting the precision of measurements, as well as provide a basis for improving the assessment of uncertainty in measurements.

  2. Dissociative, depressive, and PTSD symptom severity as correlates of nonsuicidal self-injury and suicidality in dissociative disorder patients.

    PubMed

    Webermann, Aliya R; Myrick, Amie C; Taylor, Christina L; Chasson, Gregory S; Brand, Bethany L

    2016-01-01

    The present study investigates whether symptom severity can distinguish patients diagnosed with dissociative identity disorder and dissociative disorder not otherwise specified with a recent history of nonsuicidal self-injury (NSSI) and suicide attempts from those patients without recent self-harm. A total of 241 clinicians reported on recent history of patient NSSI and suicide attempts. Of these clinicians' patients, 221 completed dissociative, depressive, and posttraumatic stress disorder symptomatology measures. Baseline cross-sectional data from a naturalistic and prospective study of dissociative disorder patients receiving community treatment were utilized. Analyses evaluated dissociative, depressive, and posttraumatic stress disorder symptom severity as methods of classifying patients into NSSI and suicide attempt groupings. Results indicated that dissociation severity accurately classified patients into NSSI and suicidality groups, whereas depression severity accurately classified patients into NSSI groups. These findings point to dissociation and depression severity as important correlates of NSSI and suicidality in patients with dissociative disorders and have implications for self-harm prevention and treatment. PMID:26211678

  3. Dissociations of the night: individual differences in sleep-related experiences and their relation to dissociation and schizotypy.

    PubMed

    Watson, D

    2001-11-01

    The author examined the associations among sleep-related experiences (e.g., hypnagogic hallucinations, nightmares, waking dreams, and lucid dreams), dissociation, schizotypy, and the Big Five personality traits in 2 large student samples. Confirmatory factor analyses indicated that (a) dissociation and schizotypy are strongly correlated-yet distinguishable-constructs, and (b) the differentiation between them can be enhanced by eliminating detachment/depersonalization items from the dissociation scales. A general measure of sleep experiences was substantially correlated with both schizotypy and dissociation (especially the latter) and more weakly related to the Big Five. In contrast, an index of lucid dreaming was weakly related to all of these other scales. These results suggest that measures of dissociation, schizotypy, and sleep-related experiences all define a common domain characterized by unusual cognitions and perceptions. PMID:11727942

  4. Anti-nociception mediated by a κ opioid receptor agonist is blocked by a δ receptor agonist

    PubMed Central

    Taylor, A M W; Roberts, K W; Pradhan, A A; Akbari, H A; Walwyn, W; Lutfy, K; Carroll, F I; Cahill, C M; Evans, C J

    2015-01-01

    BACKGROUND AND PURPOSE The opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception. EXPERIMENTAL APPROACH We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception. KEY RESULTS Etorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg−1), unmasked etorphine (3 mg·kg−1) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg−1) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg−1) and diazepam (1 mg·kg−1). CONCLUSIONS AND IMPLICATIONS Systemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles

  5. Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections

    PubMed Central

    Christopher, ME; Wong, JP

    2011-01-01

    Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.

  6. Dihydrocodeine/Agonists for Alcohol Dependents

    PubMed Central

    Ulmer, Albrecht; Müller, Markus; Frietsch, Bernhard

    2012-01-01

    Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients. Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine, Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on individual indication. This paper focuses on the data with DHC, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-steps scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details. Conclusion: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around 1/4 of the patients already. Many further

  7. Agonists and antagonists for P2 receptors

    PubMed Central

    Jacobson, Kenneth A.; Costanzi, Stefano; Joshi, Bhalchandra V.; Besada, Pedro; Shin, Dae Hong; Ko, Hyojin; Ivanov, Andrei A.; Mamedova, Liaman

    2015-01-01

    Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6 receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1 receptors. Selective non-nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X2/3/P2X3 and P2X7 receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X2/3/P2X3 receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformation-ally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose-like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1 antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50 of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4 nM at the P2Y1 receptor, with >10 000-fold selectivity in comparison to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference for the South conformation. Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed. PMID:16805423

  8. Expectations and experience: Dissociable bases for cognitive control?

    PubMed

    Bugg, Julie M; Diede, Nathaniel T; Cohen-Shikora, Emily R; Selmeczy, Diana

    2015-09-01

    Classic theories emphasized the role of expectations in the intentional control of attention and action. However, recent theorizing has implicated experience-dependent, online adjustments as the primary basis for cognitive control--adjustments that appear to be implicit (Blais, Harris, Guerrero, & Bunge, 2012). The purpose of the current study was to evaluate whether explicit expectations play any role in cognitive control above and beyond experience. In a novel precued lists paradigm, participants were administered abbreviated lists of Stroop trials. For half of the lists, precues led participants to validly expect lists of varying proportion congruency (e.g., mostly congruent [MC], mostly incongruent [MI]; Experiments 1 to 4). The Stroop effect was greater in cued MC relative to uncued MC lists. By contrast, the Stroop effect was equivalent in cued MI and uncued MI lists. Only when preparation was encouraged via a speed manipulation (Experiment 3) or incentives (Experiment 4) did we find evidence of heightened control when an MI list was expected, in the form of a short-lived reduction in the Stroop effect on the first (experience-free) trial. These patterns suggest (a) expectations play a role in the relaxation of cognitive control, independent of experience (as also shown in Experiment 5, wherein expectations were varied while holding experience constant across lists), but (b) experience is the dominant basis for the sustained heightening of cognitive control (after the first trial). Theoretical implications of dissociating the contributions of expectations and experience to cognitive control are discussed, including interpretations of the list-wide proportion congruence effect. PMID:25689002

  9. Stability constant estimator user`s guide

    SciTech Connect

    Hay, B.P.; Castleton, K.J.; Rustad, J.R.

    1996-12-01

    The purpose of the Stability Constant Estimator (SCE) program is to estimate aqueous stability constants for 1:1 complexes of metal ions with ligands by using trends in existing stability constant data. Such estimates are useful to fill gaps in existing thermodynamic databases and to corroborate the accuracy of reported stability constant values.

  10. Dissociative identity disorder: adaptive deception of self and others.

    PubMed

    Beahrs, J O

    1994-01-01

    Dissociative identity disorder (multiple personality) is increasingly diagnosed, often follows childhood trauma, and is characterized by rigidification of phenomena that resemble hypnosis. To interpret dissociated aspects of selfhood as autonomous entities is a useful heuristic; but when taken too literally, it leads to three kinds of anomaly: (1) legal: dissociators remain culpable for misdeeds carried out beyond apparent awareness or control; (2) clinical: legitimization sometimes leads not to relief, but to escalating cycles of regressive dependency; and (3) scientific: the form of dissociated entities varies with how they are defined, in ways that are intrinsically motivated and clinically manipulable. These anomalies yield to an evolutionary perspective that views dissociative identity disorder as an evolved strategy of adaptive deception of self and others; e.g., a beaten subordinate avoids further retribution by "pleading illness." Such a deceit best avoids detection when fully experienced; through its intensity and persistence, it becomes real at a new level. One's basic competencies remain intact, however, and are the source of the anomalies described. They can be clinically accessed and empowered, providing the key to therapeutic change when dissociative processes are problematic. Overall, despite clear impairment in subjective awareness and volition, dissociative-disordered individuals are best held fully accountable for the consequences of their actions. PMID:7949411

  11. Forgetting the unforgotten affective autobiographical memories in nonclinical dissociators.

    PubMed

    Chiu, Chui-De; Lin, Chi-Chin; Yeh, Yei-Yu; Hwu, Hai-Gwo

    2012-10-01

    Inefficient memory inhibition has been observed in nonclinical and clinical dissociators. Paradoxically, dissociators also report unusual forgetfulness. Investigating how forgetting emerges in dissociators may uncover the antecedents for their self-report memory problems. We postulated that set switch can link inefficient memory inhibition to forgetting. Recollection detour, which involves an affect switch, may elicit forgetting of previously uninhibited memories in nonclinical dissociators. This hypothesis was verified in participants with high- and low-dissociation proneness via a retrieval practice paradigm using positive and negative autobiographical memories. After the study and retrieval-practice phases, memories of the practiced affect category were tested without and with intervening recall of the unpracticed affect category in the control and detour condition, respectively. Nondissociators showed reduced recall in the control condition, replicating the retrieval-induced forgetting (RIF) effect and recollection detour did not alter the RIF effect. By contrast, nonclinical dissociators showed the RIF effect in the detour condition but not in the control condition. Detour to recollecting memories of another affect category rendered an aftereffect of forgetting of previously uninhibited memories in nonclinical dissociators. PMID:22023361

  12. Honokiol: A non-adipogenic PPARγ agonist from nature☆

    PubMed Central

    Atanasov, Atanas G.; Wang, Jian N.; Gu, Shi P.; Bu, Jing; Kramer, Matthias P.; Baumgartner, Lisa; Fakhrudin, Nanang; Ladurner, Angela; Malainer, Clemens; Vuorinen, Anna; Noha, Stefan M.; Schwaiger, Stefan; Rollinger, Judith M.; Schuster, Daniela; Stuppner, Hermann; Dirsch, Verena M.; Heiss, Elke H.

    2013-01-01

    Background Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators. Methods We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists. Results The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain. Conclusion We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo. General significance This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine. PMID:23811337

  13. Modification of opiate agonist binding by pertussis toxin

    SciTech Connect

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  14. Radiation therapy generates platelet-activating factor agonists

    PubMed Central

    Sahu, Ravi P.; Harrison, Kathleen A.; Weyerbacher, Jonathan; Murphy, Robert C.; Konger, Raymond L.; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R.; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F.; Travers, Jeffrey B.

    2016-01-01

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  15. Radiation therapy generates platelet-activating factor agonists.

    PubMed

    Sahu, Ravi P; Harrison, Kathleen A; Weyerbacher, Jonathan; Murphy, Robert C; Konger, Raymond L; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston, Michael Edward; Dynlacht, Joseph R; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F; Travers, Jeffrey B

    2016-04-12

    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens. PMID:26959112

  16. Henry's law constants of polyols

    NASA Astrophysics Data System (ADS)

    Compernolle, S.; Müller, J.-F.

    2014-12-01

    Henry's law constants (HLC) are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. While deriving HLC and depending on the case, also infinite dilution activity coefficients (IDACs), solid state vapour pressures or activity coefficient ratios are obtained as intermediate results. An error analysis on the intermediate quantities and the obtained HLC is included. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014), an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.

  17. Philicities, Fugalities, and Equilibrium Constants.

    PubMed

    Mayr, Herbert; Ofial, Armin R

    2016-05-17

    The mechanistic model of Organic Chemistry is based on relationships between rate and equilibrium constants. Thus, strong bases are generally considered to be good nucleophiles and poor nucleofuges. Exceptions to this rule have long been known, and the ability of iodide ions to catalyze nucleophilic substitutions, because they are good nucleophiles as well as good nucleofuges, is just a prominent example for exceptions from the general rule. In a reaction series, the Leffler-Hammond parameter α = δΔG(⧧)/δΔG° describes the fraction of the change in the Gibbs energy of reaction, which is reflected in the change of the Gibbs energy of activation. It has long been considered as a measure for the position of the transition state; thus, an α value close to 0 was associated with an early transition state, while an α value close to 1 was considered to be indicative of a late transition state. Bordwell's observation in 1969 that substituent variation in phenylnitromethanes has a larger effect on the rates of deprotonation than on the corresponding equilibrium constants (nitroalkane anomaly) triggered the breakdown of this interpretation. In the past, most systematic investigations of the relationships between rates and equilibria of organic reactions have dealt with proton transfer reactions, because only for few other reaction series complementary kinetic and thermodynamic data have been available. In this Account we report on a more general investigation of the relationships between Lewis basicities, nucleophilicities, and nucleofugalities as well as between Lewis acidities, electrophilicities, and electrofugalities. Definitions of these terms are summarized, and it is suggested to replace the hybrid terms "kinetic basicity" and "kinetic acidity" by "protophilicity" and "protofugality", respectively; in this way, the terms "acidity" and "basicity" are exclusively assigned to thermodynamic properties, while "philicity" and "fugality" refer to kinetics

  18. Constant magnification optical tracking system

    NASA Technical Reports Server (NTRS)

    Frazer, R. E. (Inventor)

    1982-01-01

    A constant magnification optical tracking system for continuously tracking of a moving object is described. In the tracking system, a traveling objective lens maintains a fixed relationship with an object to be optically tracked. The objective lens was chosen to provide a collimated light beam oriented in the direction of travel of the moving object. A reflective surface is attached to the traveling objective lens for reflecting an image of the moving object. The object to be tracked is a free-falling object which is located at the focal point of the objective lens for at least a portion of its free-fall path. A motor and control means is provided for mantaining the traveling objective lens in a fixed relationship relative to the free-falling object, thereby keeping the free-falling object at the focal point and centered on the axis of the traveling objective lens throughout its entire free-fall path.

  19. Tissue dissociation enzyme neutral protease assessment.

    PubMed

    Breite, A G; Dwulet, F E; McCarthy, R C

    2010-01-01

    Neutral proteases, essential components of purified tissue dissociation enzymes required for successful human islet isolation, show variable activities and effects of substrate on their activities. Initially we used a spectrophotometric endpoint assay with azocasein substrate to measure neutral protease activity. After critical review of the results, we observed these data to be inconsistent and not correlating expected differences in specific activities between thermolysin and Bacillus polymyxa proteases. This observation led to the development of a fluorescent microplate assay using fluorescein isothyocyanate-conjugated bovine serum albumin (FITC-BSA) as the substrate. This simpler, more flexible method offered a homogeneous, kinetic enzyme assay allowing determination of steady state reaction rates of sample replicates at various dilutions. The assay had a linear range of 4- to 8-fold and interassay coefficients of variation for B polymyxa protease and thermolysin of <9% and <15%, respectively, which were lower than those using the spectrophotometric endpoint assay, namely, 54% and 36%, respectively. This format allowed for incorporation of enzyme inhibitors, as illustrated by addition of sulfhydryl protease inhibitors, which, consistent with earlier reports, strongly indicated that the main contaminant in purified collagenase preparations was clostripain. Determination of the specific activities for several purified neutral proteases showed that the B polymyxa and Clostridium histolyticum proteases had approximately 40% and 15% specific activities, respectively, of those obtained with purified thermolysin, indicating the different characteristics of neutral protease enzymes for cell isolation procedures. PMID:20692405

  20. Activated Dissociation of HCl on Au(111).

    PubMed

    Shirhatti, Pranav R; Geweke, Jan; Steinsiek, Christoph; Bartels, Christof; Rahinov, Igor; Auerbach, Daniel J; Wodtke, Alec M

    2016-04-01

    We report zero-coverage reaction probabilities (S0) for HCl dissociative adsorption on Au(111) obtained by the seeded molecular beam hot-nozzle method. For measurements at normal incidence with mean translational energies ranging from 0.94 to 2.56 eV (nozzle temperatures 296 to 1060 K), S0 increased from 6 × 10(-6) to 2 × 10(-2). S0 also increased with increasing nozzle temperature for fixed incidence energy associated with the motion normal to the surface. Accounting for the influence of the vibrational state population and translational energy distributions in the incident beam, we are able to compare the experimental results to recent theoretical predictions. These calculations, performed employing 6-D quantum dynamics on an electronically adiabatic potential energy surface obtained using density functional theory at the level of the generalized gradient approximation and the static surface approximation, severely overestimate the reaction probabilities when compared with our experimental results. We discuss some possible reasons for this large disagreement. PMID:26990513

  1. The mechanics of motility in dissociated cytoplasm.

    PubMed Central

    Dembo, M

    1986-01-01

    We stimulate the dynamical behavior of dissociated cytoplasm using the Reactive Flow Model (Dembo, M., and F. Harlow, 1986, Biophys. J., 50:109-121). We find that for the most part the predicted dynamical behavior of the cytoplasm is governed by three nondimensional numbers. Several other nondimensional parameters, the initial conditions, and boundary conditions are found to have lesser effects. Of the three major nondimensional parameters, one (D#) controls the percentage of ectoplasm, the second (C#) controls the sharpness of the endoplasm-ectoplasm boundary, and the third (R#) controls the topological complexity of the endoplasm-ectoplasm distribution. If R# is very small, then the cytoplasm contracts into a single uniform mass, and there is no bulk streaming. If R# is very large, then the cytoplasmic mass breaks up into a number of clumps scattered throughout the available volume. Between these clumps the solution undergoes turbulent or chaotic patterns of streaming. Intermediate values of R# can be found such that the mass of cytoplasm remains connected and yet undergoes coherent modes of motility similar to flares (Taylor, D.L., J.S. Condeelis, P.L. Moore, and R.D. Allen, 1973, J. Cell Biol., 59:378-394) and rosettes (Kuroda, K., 1979, Cell Motility: Molecules and Organization, 347-362). Images FIGURE 1 FIGURE 1B FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 PMID:3801576

  2. State dissociation, human behavior, and consciousness.

    PubMed

    Mahowald, Mark W; Cramer Bornemann, Michel A; Schenck, Carlos H

    2011-01-01

    Sleep is clearly not only a whole-brain or global phenomenon, but can also be a local phenomenon. This accounts for the fact that the primary states of being (wakefulness, NREM sleep, and REM sleep) are not necessarily mutually exclusive, and components of these states may appear in various combinations, with fascinating clinical consequences. Examples include: sleep inertia, narcolepsy, sleep paralysis, lucid dreaming, REM sleep behavior disorder, sleepwalking, sleep terrors, out-of-body experiences, and reports of alien abduction. The incomplete declaration of state likewise has implications for consciousness - which also has fluid boundaries. Fluctuations in the degree of consciousness are likely explained by abnormalities of a "spatial and temporal binding rhythm" which normally results in a unified conscious experience. Dysfunctional binding may play a role in anesthetic states, autism, schizophrenia, and neurodegenerative disorders. Further study of the broad spectrum of dissociated states of sleep and wakefulness that are closely linked with states of consciousness and unconsciousness by basic neuroscientists, clinicians, and members of the legal profession will provide scientific, clinical and therapeutic insights, with forensic implications. PMID:21906025

  3. Transcultural aspects of dissociative and somatoform disorders.

    PubMed

    Escobar, J I

    1995-09-01

    A brief review of the cross-cultural literature on dissociative and somatoform disorders with emphasis on US Hispanic populations has been provided. A brief description of the psychopathology of somatizing syndromes has been given as have some critiques of current nosologic systems. Cultural influences that may color the expression of somatic manifestations have been outlined. Although it is often difficult to disentangle the contribution of ethnicity from other demographic factors, and although there are plenty of methodologic shortcomings, most studies reinforce the view that culture exerts a powerful influence in shaping symptom presentation and determining health-related attitudes. Future work using instruments such as the Composite International Diagnostic Interview (CIDI) (Rubio-Stipec M: The somatization schedule of the Composite International Diagnostic Interview: The use of the probe in 17 different countries; unpublished manuscript) that include a more culturally congruent list of somatizing symptoms may shed new light on the international distribution and mechanisms at play in these symptom presentations. PMID:8545267

  4. Dissociative recombination of rotationally cold H+3

    NASA Astrophysics Data System (ADS)

    McCall, B. J.; Huneycutt, A. J.; Saykally, R. J.; Djuric, N.; Dunn, G. H.; Semaniak, J.; Novotny, O.; Al-Khalili, A.; Ehlerding, A.; Hellberg, F.; Kalhori, S.; Neau, A.; Thomas, R. D.; Paal, A.; Österdahl, F.; Larsson, M.

    2004-11-01

    This paper presents the first dissociative recombination (DR) measurement of electrons with rotationally and vibrationally cold H+3 ions. A dc discharge pinhole supersonic jet source was developed and characterized using infrared cavity ringdown spectroscopy before installation on the CRYRING ion storage ring for the DR measurements. Rotational state distributions ( Trot ˜30 K ) produced using the source were comparable to those in the diffuse interstellar medium. Our measurement of the electron energy dependence of the DR cross section showed resonances not clearly seen in experiments using rotationally hot ions, and allowed calculation of the thermal DR rate coefficient for ions at interstellar temperatures, αDR (23 K)=2.6× 10-7 cm3 s-1 . This value is in general agreement with recent theoretical predictions by

    Kokoouline and Greene [Phys. Rev. A 68, 012703 (2003)
    ]. The branching fractions of the two breakup channels, H+H+H and H+ H2 , have also been measured for rotationally and vibrationally cold H+3 .

  5. Dissociative Recombination of Molecular Ions for Astrochemistry

    NASA Astrophysics Data System (ADS)

    Savin, Daniel W.; Novotný, O.; Becker, A.; Buhr, H.; Geppert, W.; Hamberg, M.; Krantz, C.; Kreckel, H.; Schwalm, D.; Spruck, K.; Stützel, J.; Wolf, A.; Yang, B.

    2013-06-01

    Dissociative recombination (DR) of molecular ions is a key chemical process in the cold interstellar medium (ISM). DR affects the composition, charge state, and energy balance of such environments. Astrochemical models of the ISM require reliable total DR cross sections as well as knowledge of the chemical composition and excitation states of the neutral DR products. Theory cannot reliably provide these data. We have systematically measured DR for many astrophysically relevant molecular ions utilizing the TSR storage ring at the Max-Planck-Institute for Nuclear Physics in Heidelberg, Germany. We used the merged ion-electron beam technique combined with an energy- and position-sensitive imaging detector and are able to study DR down to plasma temperatures of 10 K. The DR count rate is used to obtain absolute DR rate coefficient. Additionally we determine the masses of the DR products by measuring their kinetic energy. This allows us to assign particular DR fragmentation channels and to obtain their branching ratios. Moreover, the distribution of detected fragment distances provides information on the kinetic energy released in DR and thus also on the internal excitation of the DR products. All this information is particularly important for understanding DR of heteronuclear polyatomic ions. We will present DR results for several ions recently investigated at TSR. This work is supported in part by NASA and the NSF.

  6. Dissociable brain biomarkers of fluid intelligence.

    PubMed

    Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

    2016-08-15

    Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. PMID:27184204

  7. Dermatitis artefacta in a vulnerable adult with a dissociative state.

    PubMed

    Ahmed, A; Bewley, A; Taylor, R

    2013-12-01

    Dermatitis artefacta (DA), a factitious skin disorder, often occurs as a response to traumatic life events or as a factitious behaviour, which may result in secondary gain. It can be difficult to get patients to engage with health services, and they seldom admit to causing the lesions themselves. The possibility of DA lesions occurring in dissociative states is less well known. We present a case of DA diagnosed in a vulnerable adult, who we believe caused the lesions during periods of dissociation. We discuss the way in which the concept of dissociation can provide an acceptable way of discussing the behaviour with patients and initiating psychological therapy. PMID:23758341

  8. General features of the dissociative recombination of polyatomic molecules

    DOE PAGESBeta

    Pratt, S. T.; Jungen, Ch.; Schneider, I. F.; Dulieu, O.; Robert, J.

    2015-01-29

    We discuss some aspects of a simple expression for the low-energy dissociative recombination cross section that applies when the recombination process is dominated by the indirect mechanism. In most previous applications, this expression has been applied to capture into vibrationally excited Rydberg states with the assumption that capture is always followed by prompt dissociation. Here we consider the dissociative recombination of larger polyatomic ions and electrons. More specifically, we consider capture into electronically core-excited Rydberg states, and begin to assess its potential importance for larger systems.

  9. Isomers of various species of 1-hydroxy-2-pyridinone-6-carboxylic acid, their proton dissociation and complexes with Cr(III) and Zn(II)

    NASA Astrophysics Data System (ADS)

    Thipyapong, Khajadpai; Ruangpornvisuti, Vithaya

    2008-11-01

    Isomers of 1-hydroxy-2-pyridinone-6-carboxylic acid (6-carboxy-1,2-HOPO), their deprotonated species and complexes with chromium and zinc were theoretically investigated by density functional theory calculations. Free energy of activation, energetics, thermodynamic properties and equilibrium constants of interconversion reactions of their isomers were determined. Measured acid-dissociation constants of the 6-carboxy-1,2-HOPO obtained from potentiometric titration method were compared with the computed constants which were derived from the density functional theory method. Two isomers of each 6-carboxy-1,2-HOPO complexes with chromium and with zinc were found.

  10. Dissociative electron attachment reactions of transition metal carbonyls and their apparent influence on the thermalization of electrons by CO2

    NASA Astrophysics Data System (ADS)

    George, Patricia M.; Beauchamp, J. L.

    1982-03-01

    Dissociative electron attachment rates are measured for the transition metal carbonyls V(CO)6, Cr(CO)6, Fe(CO)5, Ni(CO)4, Mo(CO)6, and W(CO)6. Rates are measured as a function of the pressure of CO2 added to relax epithermal electrons. Derived thermal rate constants for the formation of M(CO)-n-1 from M(CO)n are 0.6, 3.0, 2.0, 2.0, 1.3, and 1.2×10-7 cm3 molecule-1 s-1, respectively. The differences in these rate constants may be attributed to the different stabilities of the molecular anion with regard to dissociation versus autodetachment. The measured rate of thermalization of electrons by CO2 varies with the metal carbonyl used and depends on the variation of the dissociative electron capture cross section with electron energy. Each system is thus tightly coupled in that the electron energy distribution is determined not only by collisional processes involving CO2 but varies as well with the energy dependent depletion of the distribution by reactant species.

  11. NON-COMPETITIVE PEAK DECAY ANALYSIS OF DRUG-PROTEIN DISSOCIATION BY HIGH-PERFORMANCE AFFINITY CHROMATOGRAPHY

    PubMed Central

    Chen, Jianzhong; Schiel, John E.; Hage, David S.

    2009-01-01

    The peak decay method is an affinity chromatographic technique that has been used to examine the dissociation of solutes from immobilized ligands in the presence of excess displacing agent. However, it can be difficult to find a displacing agent that does not interfere with detection of the eluting analyte. In this study, a non-competitive peak decay method was developed in which no displacing agent was required for analyte elution. This method was evaluated for the study of drug-protein interactions by using it along with high-performance affinity chromatography to measure the dissociation rate constants for R- and S-warfarin from columns containing immobilized human serum albumin (HSA). Several factors were considered in the optimization of this method, including the amount of applied analyte, the column size, and the flow rate. The dissociation rate constants for R- and S-warfarin from HSA were measured at several temperatures by this approach, giving values of 0.56 (± 0.01) and 0.66 (± 0.01) s−1 at pH 7.4 and 37°C. These results were in good agreement with previous values obtained by other methods. This approach is not limited to warfarin and HSA but could be employed in studying additional drug-protein interactions or other systems with weak-to-moderate binding. PMID:19472288

  12. Spectrophotometric Determination of the Dissociation Constant of an Acid-Base Indicator Using a Mathematical Deconvolution Technique

    ERIC Educational Resources Information Center

    Alter, Krystyn P.; Molloy, John L.; Niemeyer, Emily D.

    2005-01-01

    A laboratory experiment reinforces the concept of acid-base equilibria while introducing a common application of spectrophotometry and can easily be completed within a standard four-hour laboratory period. It provides students with an opportunity to use advanced data analysis techniques like data smoothing and spectral deconvolution to…

  13. Label-Free Kinetics: Exploiting Functional Hemi-Equilibrium to Derive Rate Constants for Muscarinic Receptor Antagonists.

    PubMed

    Riddy, Darren M; Valant, Celine; Rueda, Patricia; Charman, William N; Sexton, Patrick M; Summers, Roger J; Christopoulos, Arthur; Langmead, Christopher J

    2015-10-01

    Drug receptor kinetics is as a key component in drug discovery, development, and efficacy; however, determining kinetic parameters has historically required direct radiolabeling or competition with a labeled tracer. Here we present a simple approach to determining the kinetics of competitive antagonists of G protein-coupled receptors by exploiting the phenomenon of hemi-equilibrium, the state of partial re-equilibration of agonist, antagonist, and receptor in some functional assays. Using functional [Ca(2+)]i-flux and extracellular kinases 1 and 2 phosphorylation assays that have short incubation times and therefore are prone to hemi-equilibrium "behaviors," we investigated a wide range of structurally and physicochemically distinct muscarinic acetylcholine receptor antagonists. Using a combined operational and hemi-equilibrium model of antagonism to both simulate and analyze data, we derived estimates of association and dissociation rates for the test set of antagonists, identifying both rapidly dissociating (4-DAMP, himbacine) and slowly dissociating (tiotropium, glycopyrrolate) ligands. The results demonstrate the importance of assay incubation time and the degree of receptor reserve in applying the analytical model. There was an excellent correlation between estimates of antagonist pK(B), k(on), and k(off) from functional assays and those determined by competition kinetics using whole-cell [(3)H]N-methylscopolamine binding, validating this approach as a rapid and simple method to functionally profile receptor kinetics of competitive antagonists in the absence of a labeled tracer. PMID:26243731

  14. Yeast hexokinase: substrate-induced association--dissociation reactions in the binding of glucose to hexokinase P-II.

    PubMed

    Hoggett, J G; Kellett, G L

    1976-06-15

    A method is described for the purification of native hexokinases P-I and P-II from yeast using preparative isoelectric focussing to separate the isozymes. The binding of glucose to hexokinase P-II, and the effect of this on the monomer--dimer association--dissociation reaction have been investigated quantitatively by a combination of titrations of intrinsic protein fluorescence and equilibrium ultracentrifugation. Association constants for the monomer-dimer reaction decreased with increasing pH, ionic strength and concentration of glucose. Saturating concentrations of glucose did not bring about complete dissociation of the enzyme showing that both sites were occupired in the dimer. At pH 8.0 and high ionic strength, where the enzyme existed as monomer, the dissociation constant of the enzyme-glucose complex was 3 X 10(-4) mol 1(-1) and was independent of the concentration of enzyme. Binding to the dimeric form at low pH and ionic strength (I=0.02 mol 1(-1), pH less than 7.5) was also independent of enzyme concentration (in the range 10-1000 mug ml-1) but was much weaker. The process could be described by a single dissociation constant, showing that the two available sites on the dimer were equivalent and non-cooperative; values of the intrinsic dissociation constant varied from 2.5 X 10(-3) mol 1(-1) at pH 7.0 to 6 X 10(-3) at pH 6.5. Under intermediate conditions (pH 7.0, ionic strength=0.15 mol 1(-1)), where monomer and dimer coexisted, the binding of glucose showed weak positive cooperatively (Hill coefficient 1.2); in addition, the binding was dependent upon the concentration of enzyme in the direction of stronger binding at lower concentrations. The results show that the phenomenon of half-sites reactivity observed in the binding of glucose to crystalline hexokinase P-II does not occur in solution; the simplest explanation of our finding the two sites to be equivalent is that the dimer results from the homologous association of two identical subunits. PMID

  15. Dissociation of I II in chemical oxygen-iodine lasers: experiment, modeling, and pre-dissociation by electrical discharge

    NASA Astrophysics Data System (ADS)

    Katz, A.; Waichman, K.; Dahan, Z.; Rybalkin, V.; Barmashenko, B. D.; Rosenwaks, S.

    2007-06-01

    The dissociation of I II molecules at the optical axis of a supersonic chemical oxygen-iodine laser (COIL) was studied via detailed measurements and three dimensional computational fluid dynamics calculations. Comparing the measurements and the calculations enabled critical examination of previously proposed dissociation mechanisms and suggestion of a mechanism consistent with the experimental and theoretical results obtained in a supersonic COIL for the gain, temperature and I II dissociation fraction at the optical axis. The suggested mechanism combines the recent scheme of Azyazov and Heaven (AIAA J. 44, 1593 (2006)), where I II(A' 3Π 2u), I II(A 3Π 1u) and O II(a1Δ g, v) are significant dissociation intermediates, with the "standard" chain branching mechanism of Heidner et al. (J. Phys. Chem. 87, 2348 (1983)), involving I(2P 1/2) and I II(X1Σ + g, v). In addition, we examined a new method for enhancement of the gain and power in a COIL by applying DC corona/glow discharge in the transonic section of the secondary flow in the supersonic nozzle, dissociating I II prior to its mixing with O II(1Δ). The loss of O II(1Δ) consumed for dissociation was thus reduced and the consequent dissociation rate downstream of the discharge increased, resulting in up to 80% power enhancement. The implication of this method for COILs operating beyond the specific conditions reported here is assessed.

  16. Narratives of dissociation: insights into the treatment of dissociation in individuals who were sexually abused as children.

    PubMed

    Hirakata, Pam

    2009-01-01

    This article provides an in-depth understanding of the treatment of dissociation from the perspective of 7 individuals who have a history of childhood sexual abuse and engage in moderate to high levels of dissociative behavior. Levels of dissociation were screened using the Dissociative Experiences Scale (E. Bernstein-Carlson & F. Putnam, 1993), and individual interviews were conducted to gain insight into how dissociation can best be treated in a therapeutic context. From a narrative research design with a holistic-content analysis (A. Lieblich, R. Tuval-Mashiach, & T. Zilber, 1998), 3 major themes and 16 subthemes were revealed. The major themes included (a) identifying specific tools and techniques that were recognized as critical in managing dissociative symptoms, (b) challenging the dominant medical paradigm by underscoring the importance of helping clients contextualize and normalize dissociative behavior, and (c) highlighting specific characteristics of the therapeutic relationship that create the necessary trust and safety to facilitate reparation. A detailed description of the 3 major themes and 16 subthemes is provided. Implications for both clinical theory and practice are identified. PMID:19585338

  17. Supra-physiological efficacy at GPCRs: superstition or super agonists?

    PubMed Central

    Langmead, Christopher J; Christopoulos, Arthur

    2013-01-01

    The concept of ‘super agonism’ has been described since the discovery of peptide hormone analogues that yielded greater functional responses than the endogenous agonists, in the early 1980s. It has remained an area of debate as to whether such compounds can really display greater efficacy than an endogenous agonist. However, recent pharmacological data, combined with crystal structures of different GPCR conformations and improved analytical methods for quantifying drug action, are starting to shed light on this phenomenon and indicate that super agonists may be more than superstition. Linked Article This article is a commentary on Schrage et al., pp. 357–370 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12003 PMID:23441648

  18. Principles of agonist recognition in Cys-loop receptors

    PubMed Central

    Lynagh, Timothy; Pless, Stephan A.

    2014-01-01

    Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine, and GABA. After the term “chemoreceptor” emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands. PMID:24795655

  19. Alpha-2 agonists as pain therapy in horses.

    PubMed

    Valverde, Alexander

    2010-12-01

    Alpha-2 agonists, such as xylazine, clonidine, romifidine, detomidine, medetomidine, and dexmedetomidine, are potent analgesic drugs that also induce physiologic and behavioral changes, such as hypertension, bradycardia, atrioventricular block, excessive sedation and ataxia, all of which can potentially limit their systemic use as analgesics in some clinical cases. The use of medetomidine and dexmetomidine has been introduced for equine anesthesia/analgesia, and although not approved in this species, their increased specificity for alpha-2 receptors may offer some potential advantages over the traditional alpha-2 agonists. Similarly, other routes of administration and benefits of alpha-2 agonists are recognized in the human and laboratory animal literature, which may prove useful in the equine patient if validated in the near future. This review presents this relevant information. PMID:21056297

  20. Final report. Surface-induced dissociation versus collision-induced dissociation

    SciTech Connect

    Futrell, Jean H.

    2001-04-19

    A 7-Tesla Fourier transform ion-cyclotron resonance (FTICR) mass spectrometer was modified to insert a surface inside the cell for ion-surface collisions leading to the dissociation of impacting ions. Modifications were made to the software/hardware to collide the ions brought into the cell and trap the resulting fragment and undissociated primary ions inside the cell. The trapping plates were also ramped to determine kinetic energy distributions of these ions. The surface-induced dissociation (SID) of benzene and chromium hexacarbonyl ions was first studied as test cases for the instrument. Then a systematic study of the SID of small protonated peptides formed by electrospray ionization was begun. A series of small alanine(A)-containing peptides, viz., AA, AAA, AAAA, AAAAA, and PAAAA were used in the study. In the absence of any direct comparisons of the SID processes with the commonly used technique of tandem mass spectrometry of collision-induced dissociations (CID) via collisions with a neutral gas, a comparative study of CID and SID using the same protonated peptides was made. Since multiple collisions are often used to enhance dissociation efficiency in CID, the CID was performed under single as well as multiple collisional activation conditions. Both on-resonance and sustained off-resonance irradiation excitation were used for CID experiments. Kinetic energy of the ions was varied by changing peak-to-peak voltage applied to the excitation plates. Results are shown in a series of graphs, and a simple theoretical model is presented. This direct comparison of the two activation techniques on the same instrument provided insights into the similarities and differences between these two. The results suggest that internal energy distributions of ions activated by ion-surface collision and multiple collision ion-gaseous neutral collisions are quite comparable. The results also suggest that, in ion-surface collisions, the ion collides with only a small fraction of th

  1. Effect of long-term infusion of an LH-releasing hormone agonist on testicular function in bulls.

    PubMed

    von Rechenberg, W; Sandow, J; Klatt, P

    1986-05-01

    Continuous administration of LH-releasing hormone (LHRH) agonists is an effective method of suppressing testosterone secretion in the male. The effect of the LH-releasing hormone (LHRH) agonist, buserelin, administered to bulls by constant infusion from osmotic minipumps was studied. In one experiment with four treated and one control bull, 109 micrograms buserelin/day were administered for 22 days. Immediately after implantation, serum testosterone concentrations rose from below 35 nmol/l to 35-105 nmol/l, and all four buserelin-infused bulls showed increased testosterone secretion during the treatment period. After removal of the minipumps, testosterone concentrations decreased to pretreatment levels. In a second experiment bulls were infused for 42 days (four treated and one control), and identical results were obtained. Testosterone secretion was stimulated (52-87 nmol/l serum) during the entire treatment period. These results demonstrate that conditions for stimulation of the pituitary-testicular axis may vary between species. Infusion of low doses of LHRH-agonists in bulls has an extended stimulatory effect without immediate desensitization of gonadotrophin release. PMID:3086475

  2. Dissociative amnesia in dissociative disorders and borderline personality disorder: self-rating assessment in a college population.

    PubMed

    Sar, Vedat; Alioğlu, Firdevs; Akyuz, Gamze; Karabulut, Sercan

    2014-01-01

    Dissociative amnesia (DA) among subjects with a dissociative disorder and/or borderline personality disorder (BPD) recruited from a nonclinical population was examined. The Steinberg Dissociative Amnesia Questionnaire (SDAQ), the Childhood Trauma Questionnaire, and the self-report screening tool of the BPD section of the Structured Clinical Interview for DSM-IV(SCID-BPD) were administered to 1,301 college students. A total of 80 participants who were diagnosed with BPD according to the clinician-administered SCID-BPD and 111 nonborderline controls were evaluated using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) by a psychiatrist blind to diagnosis and scale scores. Internal consistency analyses and test-retest evaluations suggested that the SDAQ is a reliable instrument for the population studied. Of the participants, 20.6% reported an SDAQ score of 20 or above and impairment by DA. Those who had both dissociative disorder and BPD (n = 78) had the highest SDAQ scores. Both disorders had significant effects on the SCID-D total and amnesia scores in the variance analysis. On SDAQ scores, however, only BPD had this effect. There was a significant interaction between the 2 disorders for the SCID-D total but not for the SDAQ or SCID-D amnesia scores. BPD represented the severity of dissociation and childhood trauma in this study group. However, in contrast to the dissociative disorders, BPD was characterized by better awareness of DA in self-report. The discrepancies between self-report and clinical interview associated with BPD and dissociative disorders are discussed in the context of betrayal theory (J. J. Freyd, 1994) of BPD and perceptual theory (D. B. Beere, 2009) of dissociative disorders. PMID:24678926

  3. Dissociation between systemic and pulmonary anti‐inflammatory effects of dexamethasone in humans

    PubMed Central

    Bartko, Johann; Stiebellehner, Leopold; Derhaschnig, Ulla; Schoergenhofer, Christian; Schwameis, Michael; Prosch, Helmut

    2016-01-01

    Aims The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. Methods In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Results Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. Conclusions The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other. PMID:26647918

  4. Agonist treatment in opioid use: advances and controversy.

    PubMed

    Viswanath, Biju; Chand, Prabhat; Benegal, Vivek; Murthy, Pratima

    2012-06-01

    Opioid dependence is a chronic relapsing condition which requires comprehensive care; pharmacological agents form the mainstay of its long term treatment. The two most popular approaches are the harm reduction method using agonists and the complete abstinence method using antagonists. Currently, particularly from the harm minimization perspective and the low feasibility of an abstinence based approach, there is an increasing trend toward agonist treatment. The use of buprenorphine has gained popularity in view of its safety profile and the availability of the buprenorphine-naloxone combination has made it popular as a take-home treatment. This review outlines the pharmacological advances and controversies in this area. PMID:22813654

  5. Insect Nicotinic Receptor Agonists as Flea Adulticides in Small Animals

    PubMed Central

    Vo, Dai Tan; Hsu, Walter H.; Martin, Richard J.

    2013-01-01

    Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as fleacides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and spinosad. Insect nAChR agonists are one of the most important new classes of insecticides, which are used to control sucking insects both on plants and on companion animals. These new compounds provide a new approach for practitioners to safely and effectively eliminate fleas. PMID:20646191

  6. Piperidine derivatives as nonprostanoid IP receptor agonists 2.

    PubMed

    Hayashi, Ryoji; Ito, Hiroaki; Ishigaki, Takeshi; Morita, Yasuhiro; Miyamoto, Mitsuko; Isogaya, Masafumi

    2016-06-15

    We searched for a strong and selective nonprostanoid IP agonist bearing piperidine and benzanilide moieties. Through optimization of substituents on the benzanilide moiety, the crucial part of the agonist, 43 (2-((1-(2-(N-(4-tolyl)benzo[d][1,3]dioxole-5-carboxamido)ethyl)piperidin-4-yl)oxy)acetic acid monohydrate monohydrochloride) was discovered and exhibited strong platelet aggregation inhibition (IC50=21nM) and 100-fold selectivity for IP receptor over other PG receptors. The systemic exposure level and bioavailability after oral administration of 43 were also good in dog. PMID:27133594

  7. Is There a Cosmological Constant?

    NASA Technical Reports Server (NTRS)

    Kochanek, Christopher; Oliversen, Ronald J. (Technical Monitor)

    2002-01-01

    The grant contributed to the publication of 18 refereed papers and 5 conference proceedings. The primary uses of the funding have been for page charges, travel for invited talks related to the grant research, and the support of a graduate student, Charles Keeton. The refereed papers address four of the primary goals of the proposal: (1) the statistics of radio lenses as a probe of the cosmological model (#1), (2) the role of spiral galaxies as lenses (#3), (3) the effects of dust on statistics of lenses (#7, #8), and (4) the role of groups and clusters as lenses (#2, #6, #10, #13, #15, #16). Four papers (#4, #5, #11, #12) address general issues of lens models, calibrations, and the relationship between lens galaxies and nearby galaxies. One considered cosmological effects in lensing X-ray sources (#9), and two addressed issues related to the overall power spectrum and theories of gravity (#17, #18). Our theoretical studies combined with the explosion in the number of lenses and the quality of the data obtained for them is greatly increasing our ability to characterize and understand the lens population. We can now firmly conclude both from our study of the statistics of radio lenses and our survey of extinctions in individual lenses that the statistics of optically selected quasars were significantly affected by extinction. However, the limits on the cosmological constant remain at lambda < 0.65 at a 2-sigma confidence level, which is in mild conflict with the results of the Type la supernova surveys. We continue to find that neither spiral galaxies nor groups and clusters contribute significantly to the production of gravitational lenses. The lack of group and cluster lenses is strong evidence for the role of baryonic cooling in increasing the efficiency of galaxies as lenses compared to groups and clusters of higher mass but lower central density. Unfortunately for the ultimate objective of the proposal, improved constraints on the cosmological constant, the next

  8. A novel single-molecule study to determine protein--protein association constants.

    PubMed

    Ratcliff, G C; Erie, D A

    2001-06-20

    Atomic force microscopy (AFM) is traditionally used as an imaging technique to gain qualitative information for a biological system. We have successfully used the imaging capabilities of the AFM to determine protein-protein association constants. We have developed a method to measure the molecular weight of a protein based on its volume determined from AFM images. Our volume determination method allows for rapid, accurate analysis of large protein populations. On the basis of the measured volume, the fraction of monomers as dimers was determined for the DNA helicase UvrD, and the dissociation constant (K(d)) for the helicase was calculated. We determined a K(d) for UvrD of 1.4 microM, which is in good agreement with published K(d) data obtained from analytical ultracentrifugation (AUC) studies. Our method provides a rapid method for determining protein-protein association constants. PMID:11403593

  9. Pulse radiolytic study of the acid dissociation of OH protons in radicals related to salicylic acid

    SciTech Connect

    Sun, Q.; Schuler, R.H.

    1987-08-13

    The deprotonation of carboxylated benzosemiquinone radicals prepared by pulse radiolytic oxidation of dihydroxybenzoic acids has been examined by time-resolved absorption spectrophotometry. The pK/sub a/ for dissociation of the OH proton in 3-carboxyl-1,4-benzosemiquinone is found to be 6.47 or 2.4 units higher than that in the unsubstituted radical. This pK/sub a/ is, however, well below that of the OH proton in salicyclic acid (13.6) so that hydrogen bonding is appreciably decreased by the delocalization of the unpaired spin in this radical. Protonation of the basic form of the radical occurs at the diffusion-controlled rate. The rate constant for deprotonation by OH/sup -/ is relatively low, 4.7 X 10/sup 7/ M/sup -1/ s/sup -1/, so that reaction with base becomes important only above pH 10. As a result this radical provides an excellent system for studying acid-base equilibration processes in near neutral solutions. Azide ion is shown to be an efficient catalyst which allows the acid-base equilibrium to be examined on the 10-..mu..s time scale. Deprotonation is also catalyzed by the dihydroxybenzoic acid used as the radical source. Analogous studies on 4-carboxy-1,3-benzosemiquinone give the pK/sub a/ as 7.9. In spite of this high pK/sub a/, which indicates the rate constant for spontaneous dissociation of this radical to be > 10/sup 3/ s/sup -1/, the rate constant for deprotonation by OH/sup -/, 4.9 X 10/sup 8/ M/sup -1/ s/sup -1/, is considerably higher than in the case of 3-carboxy-1,4-benzosemiquinone.

  10. Cognitive therapy of dissociative symptoms associated with trauma.

    PubMed

    Kennerley, H

    1996-09-01

    The presentation of dissociative symptoms is not uncommon in clinical settings, particularly when the client has suffered trauma. The phenomenon of dissociation ranges from benign incidents, such as daydreaming, to potentially life-threatening experiences when it precipitates self-harm. Its presentation may be subtle, belying the distress which it can provoke. Cognitive therapists are well equipped to help clients formulate a working conceptualization of the dissociative episode and to develop a range of coping skills to manage and overcome the experience. This paper discusses practical ways in which the cognitive therapist can use standard and schema-focused cognitive therapy to help clients to better deal with the distressing aspects of dissociation. PMID:8889075

  11. Dissociative electron attachment to the radiosensitizing chemotherapeutic agent hydroxyurea.

    PubMed

    Huber, S E; Śmiałek, M A; Tanzer, K; Denifl, S

    2016-06-14

    Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its radiosensitizing capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO(-), water, and the amidogen (NH2) radical. The second and third most dominant dissociation channels are associated with formation of NCNH(-) and NHCONH2 (-), respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH2 (-)/O(-), OH(-), CN(-), HNOH(-), NCONH2 (-), and ONHCONH2 (-). PMID:27306009

  12. Dissociative electron attachment to the radiosensitizing chemotherapeutic agent hydroxyurea

    NASA Astrophysics Data System (ADS)

    Huber, S. E.; Śmiałek, M. A.; Tanzer, K.; Denifl, S.

    2016-06-01

    Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its radiosensitizing capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO-, water, and the amidogen (NH2) radical. The second and third most dominant dissociation channels are associated with formation of NCNH- and NHCONH2-, respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH2-/O-, OH-, CN-, HNOH-, NCONH2-, and ONHCONH2-.

  13. Rates for dissociative recombination of LiH+ ions

    NASA Astrophysics Data System (ADS)

    Čurík, R.; Greene, C. H.

    2008-05-01

    We review recent progress in developing a theoretical treatment of the dissociative recombination (DR) process for the LiH+ molecule, in which a low energy electron is captured and causes the molecule to dissociate into neutral fragments. This e+LiH+ system is prototypical of the indirect class of DR processes, in which the incident electron destroys the molecule through Rydberg capture pathways. The conventional mechanism characteristic of most species with a high DR rate, which normally involves direct capture into a dissociative resonance potential curve, is entirely absent here. We have adopted ab initio multichannel quantum defect theory (MQDT) and a rovibrational frame transformation based on Siegert pseudostates to calculate indirect dissociative recombination for this simple diatomic ion. It is based on a set of ab-initio quantum defects as functions of the internuclear distance, which have been calculated using the R-matrix approach. The calculated DR rate coefficient is found to agree with recent experimental data [1].

  14. Catalytic efficiency of Nb and Nb oxides for hydrogen dissociation

    SciTech Connect

    Isobe, Shigehito; Kudoh, Katsuhiro; Hino, Satoshi; Hashimoto, Naoyuki; Ohnuki, Somei; Hara, Kenji

    2015-08-24

    In this letter, catalytic efficiency of Nb, NbO, Nb{sub 2}O{sub 3}, NbO{sub 2}, and Nb{sub 2}O{sub 5} for dissociation and recombination of hydrogen were experimentally investigated. On the surface of Nb and Nb oxides in a gas mixture of H{sub 2} and D{sub 2}, H{sub 2} and D{sub 2} molecules can be dissociated to H and D atoms; then, H{sub 2}, D{sub 2}, and HD molecules can be produced according to the law of probability. With increase of frequency of the dissociation and recombination, HD ratio increases. The ratio of H{sub 2} and HD gas was analyzed by quadrupole mass spectrometry. As a result, NbO showed the highest catalytic activity towards hydrogen dissociation and recombination.

  15. How Many Water Molecules Does it Take to Dissociate HCl?

    PubMed

    Vargas-Caamal, Alba; Cabellos, Jose Luis; Ortiz-Chi, Filiberto; Rzepa, Henry S; Restrepo, Albeiro; Merino, Gabriel

    2016-02-18

    The potential energy surfaces of the HCl(H2O)n (n is the number of water molecules) clusters are systematically explored using density functional theory and high-level ab initio computations. On the basis of electronic energies, the number of water molecules needed for HCl dissociation is four as reported by some experimental groups. However, this number is five owing to the inclusion of entropic factors. Wiberg bond indices are calculated and analyzed, and the results provide a quadratic correlation and classification of clusters according to the nondissociated, partially dissociated, and fully dissociated character of the H-Cl bond. Our computations show that if temperature is not controlled during the experiment, the values obtained for the dipole moment (or for any measurable property) are susceptible to change, providing a different picture of the number of water molecules needed for HCl dissociation in a nanoscopic droplet. PMID:26774026

  16. Negligible Isotopic Effect on Dissociation of Hydrogen Bonds.

    PubMed

    Ge, Chuanqi; Shen, Yuneng; Deng, Gang-Hua; Tian, Yuhuan; Yu, Dongqi; Yang, Xueming; Yuan, Kaijun; Zheng, Junrong

    2016-03-31

    Isotopic effects on the formation and dissociation kinetics of hydrogen bonds are studied in real time with ultrafast chemical exchange spectroscopy. The dissociation time of hydrogen bond between phenol-OH and p-xylene (or mesitylene) is found to be identical to that between phenol-OD and p-xylene (or mesitylene) in the same solvents. The experimental results demonstrate that the isotope substitution (D for H) has negligible effects on the hydrogen bond kinetics. DFT calculations show that the isotope substitution does not significantly change the frequencies of vibrational modes that may be along the hydrogen bond formation and dissociation coordinate. The zero point energy differences of these modes between hydrogen bonds with OH and OD are too small to affect the activation energy of the hydrogen bond dissociation in a detectible way at room temperature. PMID:26967376

  17. Communication: Enhanced dissociative chemisorption of CO2 via vibrational excitation

    NASA Astrophysics Data System (ADS)

    Jiang, Bin; Guo, Hua

    2016-03-01

    A fully coupled global nine-dimensional potential energy surface for the dissociative chemisorption of CO2 on Ni(100) is constructed from ˜18 000 density functional points. It reveals a complex reaction pathway dominated by two near iso-energetic transition states. The dissociation probabilities obtained by quasi-classical trajectories on the potential energy surface reproduced experimental trends, and indicate that vibrational excitations of CO2 significantly promote the dissociation. Using the sudden vector projection model, the behavior of the reactivity is rationalized by couplings with the reaction coordinate at each transition state. These results offer plausible rationalization for the observed enhancement of CO2 dissociation in non-thermal plasmas by metal surfaces.

  18. Communication: Enhanced dissociative chemisorption of CO2 via vibrational excitation.

    PubMed

    Jiang, Bin; Guo, Hua

    2016-03-01

    A fully coupled global nine-dimensional potential energy surface for the dissociative chemisorption of CO2 on Ni(100) is constructed from ∼18,000 density functional points. It reveals a complex reaction pathway dominated by two near iso-energetic transition states. The dissociation probabilities obtained by quasi-classical trajectories on the potential energy surface reproduced experimental trends, and indicate that vibrational excitations of CO2 significantly promote the dissociation. Using the sudden vector projection model, the behavior of the reactivity is rationalized by couplings with the reaction coordinate at each transition state. These results offer plausible rationalization for the observed enhancement of CO2 dissociation in non-thermal plasmas by metal surfaces. PMID:26957149

  19. Pyrrolo- and Pyridomorphinans: Non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists

    PubMed Central

    Kumar, V.; Clark, M.J.; Traynor, J.R.; Lewis, J.W.; Husbands, S.M.

    2014-01-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist activity at delta opioid receptors but not at mu and/or kappa opioid receptors and in that sense profiled as a selective delta opioid receptor agonist. The pyridomorphinans derived from naltrexone and naloxone were all found to be non-selective potent antagonists and as such could have utility as treatments for alcohol abuse. PMID:24973818

  20. Pyrrolo- and pyridomorphinans: non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists.

    PubMed

    Kumar, V; Clark, M J; Traynor, J R; Lewis, J W; Husbands, S M

    2014-08-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist activity at delta opioid receptors but not at mu and/or kappa opioid receptors and in that sense profiled as a selective delta opioid receptor agonist. The pyridomorphinans derived from naltrexone and naloxone were all found to be non-selective potent antagonists and as such could have utility as treatments for alcohol abuse. PMID:24973818