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Sample records for ps-1 rate constant

  1. The OsPS1-F gene regulates growth and development in rice by modulating photosynthetic electron transport rate.

    Science.gov (United States)

    Ramamoorthy, Rengasamy; Vishal, Bhushan; Ramachandran, Srinivasan; Kumar, Prakash P

    2017-11-17

    Ds insertion in rice OsPS1-F gene results in semi-dwarf plants with reduced tiller number and grain yield, while genetic complementation with OsPS1-F rescued the mutant phenotype. Photosynthetic electron transport is regulated in the chloroplast thylakoid membrane by multi-protein complexes. Studies about photosynthetic machinery and its subunits in crop plants are necessary, because they could be crucial for yield enhancement in the long term. Here, we report the characterization of OsPS1-F (encoding Oryza sativa PHOTOSYSTEM 1-F subunit) using a single copy Ds insertion rice mutant line. The homozygous mutant (osps1-f) showed striking difference in growth and development compared to the wild type (WT), including, reduction in plant height, tiller number, grain yield as well as pale yellow leaf coloration. Chlorophyll concentration and electron transport rate were significantly reduced in the mutant compared to the WT. OsPS1-F gene was highly expressed in rice leaves compared to other tissues at different developmental stages tested. Upon complementation of the mutant with proUBI::OsPS1-F, the observed mutant phenotypes were rescued. Our results illustrate that OsPS1-F plays an important role in regulating proper growth and development of rice plants.

  2. Arrhenius Rate: constant volume burn

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-12-06

    A constant volume burn occurs for an idealized initial state in which a large volume of reactants at rest is suddenly raised to a high temperature and begins to burn. Due to the uniform spatial state, there is no fluid motion and no heat conduction. This reduces the time evolu tion to an ODE for the reaction progress variable. With an Arrhenius reaction rate, two characteristics of thermal ignition are illustrated: induction time and thermal runaway. The Frank-Kamenetskii approximation then leads to a simple expression for the adiabatic induction time. For a first order reaction, the analytic solution is derived and used to illustrate the effect of varying the activation temperature; in particular, on the induction time. In general, the ODE can be solved numerically. This is used to illustrate the effect of varying the reaction order. We note that for a first order reaction, the time evolution of the reaction progress variable has an exponential tail. In contrast, for a reaction order less than one, the reaction completes in a nite time. The reaction order also affects the induction time.

  3. Rate constants, timescales, and free energy barriers

    Science.gov (United States)

    Salamon, Peter; Wales, David; Segall, Anca; Lai, Yi-An; Schön, J. Christian; Hoffmann, Karl Heinz; Andresen, Bjarne

    2016-01-01

    The traditional connection between rate constants and free energy landscapes is extended to define effective free energy landscapes relevant on any chosen timescale. Although the Eyring-Polanyi transition state theory specifies a fixed timescale of τ=h/kBT}, we introduce instead the timescale of interest for the system in question, e.g. the observation time. The utility of drawing such landscapes using a variety of timescales is illustrated by the example of Holliday junction resolution. The resulting free energy landscapes are easier to interpret, clearly reveal observation time dependent effects like coalescence of short-lived states, and reveal features of interest for the specific system more clearly.

  4. An Introduction to Collision Theory Rate Constants via Distribution Functions.

    Science.gov (United States)

    McAlduff, E. J.

    1980-01-01

    Described is an introduction to the collision theory by arriving at the many degrees of freedom rote constant and showing that the (-Ea/RT) is a special case and corresponds to activation in 2 squared terms on the line of center rate constant, which is found through the use of distributed functions. (Author/DS)

  5. Determination of Biological Oxygen Demand Rate Constant and ...

    African Journals Online (AJOL)

    Determination of Biological Oxygen Demand Rate Constant and Ultimate Biological Oxygen Demand for Liquid Waste Generated from Student Cafeteria at Jimma University: A Tool for Development of Scientific Criteria to Protect Aquatic Health in the Region.

  6. Early temporal short-term memory deficits in double transgenic APP/PS1 mice.

    Science.gov (United States)

    Lagadec, Saioa; Rotureau, Lolita; Hémar, Agnès; Macrez, Nathalie; Delcasso, Sebastien; Jeantet, Yannick; Cho, Yoon H

    2012-01-01

    We tested single APP (Tg2576) transgenic, PS1 (PS1dE9) transgenic, and double APP/PS1 transgenic mice at 3 and 6 months of age on the acquisition of a hippocampal-dependent operant "differential reinforcement of low rate schedule" (DRL) paradigm. In this task mice are required to wait for at least 10 seconds (DRL-10s) between 2 consecutive nose poke responses. Our data showed that while single APP and PS1 transgene expression did not affect DRL learning and performance, mice expressing double APP/PS1 transgenes were impaired in the acquisition of DRL-10s at 6 months, but not at 3 months of age. The same impaired double transgenic mice, however, were perfectly capable of normal acquisition of signaled DRL-10s (SDRL-10s) task, a hippocampal-independent task, wherein mice were required to emit responses when the end of the 10-second delay was signaled by a lighting of the chamber. The age-dependent and early deficits of APP/PS1 mice suggest that the appetitive DRL paradigm is sensitive to the amyloid pathology present in double APP/PS1 mice, and that this mouse line represents a good model with which to study the efficacy of therapeutic strategies against Alzheimer's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Quantum corrections to the equilibrium rate constants of inelastic processes

    Energy Technology Data Exchange (ETDEWEB)

    Eletskii, Aleksandr V [Russian Research Centre ' Kurchatov Institute' , Moscow (Russian Federation); Starostin, Andrei N; Taran, Mikhail D [State Research Center of Russian Federation ' Troitsk Institute for Innovation and Fusion Research' , Troitsk, Moscow Region (Russian Federation)

    2005-03-31

    The quantum corrections which the equilibrium rate constants of inelastic processes acquire due to particle momenta deviating from the Maxwell distribution at high gas pressures and relatively low temperatures are considered. This deviation can be interpreted as a manifestation of the time-energy uncertainty relation for particles colliding elastically at a high rate, with the characteristic energy {approx}h{nu} (where {nu} is the collision frequency) put into correspondence with the temperature. Taking account of this deviation changes the temperature dependences of the rate constants of adiabatic and exothermal processes, as illustrated by the examples of vibrationally relaxing diatomic molecules and nuclear fusion and chemical processes. The experimental anomalies in the temperature dependences of the corresponding rate constants are accounted for adequately by introducing the non-Maxwellian corrections. (methodological notes)

  8. Rate constant for reaction of atomic hydrogen with germane

    Science.gov (United States)

    Nava, David F.; Payne, Walter A.; Marston, George; Stief, Louis J.

    1990-01-01

    Due to the interest in the chemistry of germane in the atmospheres of Jupiter and Saturn, and because previously reported kinetic reaction rate studies at 298 K gave results differing by a factor of 200, laboratory measurements were performed to determine the reaction rate constant for H + GeH4. Results of the study at 298 K, obtained via the direct technique of flash photolysis-resonance fluorescence, yield the reaction rate constant, k = (4.08 + or - 0.22) x 10(exp -12) cu cm/s.

  9. Charring rate of wood exposed to a constant heat flux

    Science.gov (United States)

    R. H. White; H. C. Tran

    1996-01-01

    A critical factor in the fire endurance of a wood member is its rate of charring. Most available charring rate data have been obtained using the time-temperature curves of the standard fire resistance tests (ASTM E 119 and ISO 834) to define the fire exposure. The increased use of heat release calorimeters using exposures of constant heat flux levels has broadened the...

  10. A Comparative Study of the Drying Rate Constant, Drying Efficiency ...

    African Journals Online (AJOL)

    The adoption of the drying techniques would ensure steady availability of these vegetables all the year round as well as reduce carbon emissions from the conventional drying methods and hence mitigate global warming. KEYWORDS: Solar drying, open- air sun drying, drying rate constant, falling rate, climate change, food ...

  11. Reaction rate constant for radiative association of CF+

    Science.gov (United States)

    Ã-ström, Jonatan; Bezrukov, Dmitry S.; Nyman, Gunnar; Gustafsson, Magnus

    2016-01-01

    Reaction rate constants and cross sections are computed for the radiative association of carbon cations (C+) and fluorine atoms (F) in their ground states. We consider reactions through the electronic transition 11Π → X1Σ+ and rovibrational transitions on the X1Σ+ and a3Π potentials. Semiclassical and classical methods are used for the direct contribution and Breit-Wigner theory for the resonance contribution. Quantum mechanical perturbation theory is used for comparison. A modified formulation of the classical method applicable to permanent dipoles of unequally charged reactants is implemented. The total rate constant is fitted to the Arrhenius-Kooij formula in five temperature intervals with a relative difference of <3%. The fit parameters will be added to the online database KIDA. For a temperature of 10-250 K, the rate constant is about 10-21 cm3 s-1, rising toward 10-16 cm3 s-1 for a temperature of 30 000 K.

  12. Distribution of adhesion rate constant in the coal sample

    Directory of Open Access Journals (Sweden)

    Marian Brožek

    2005-11-01

    Full Text Available Flotation is the process of enrichment which consists in differentiating the useful component (volume property in the separation products. Flotation leads to the differentiation of the volume property by means of applying the differentiation of surface properties. Since there is a correlation between these properties, the authors determined the distribution of adhesion rate constant in relation with the content of the useful component and applying the dispersive model of a particle. The content of the useful component is directly connected with the volume physical property, represented by particle density. The paper present distribution functions of density and adhesion rate constant in the sample. Also the relation between adhesion rate constant and ash content for narrow density fractions has been revealed.

  13. Impact of Constant Rate Factor on Objective Video Quality Assessment

    Directory of Open Access Journals (Sweden)

    Juraj Bienik

    2017-01-01

    Full Text Available This paper deals with the impact of constant rate factor value on the objective video quality assessment using PSNR and SSIM metrics. Compression efficiency of H.264 and H.265 codecs defined by different Constant rate factor (CRF values was tested. The assessment was done for eight types of video sequences depending on content for High Definition (HD, Full HD (FHD and Ultra HD (UHD resolution. Finally, performance of both mentioned codecs with emphasis on compression ratio and efficiency of coding was compared.

  14. APP/PS1 transgenic mice treated with aluminum: an update of Alzheimer's disease model.

    Science.gov (United States)

    Zhang, Q L; Jia, L; Jiao, X; Guo, W L; Ji, J W; Yang, H L; Niu, Q

    2012-01-01

    There is still no animal model available that can mimic all the cognitive, behavioral, biochemical, and histopathological abnormalities observed in patients with Alzheimer's disease (AD). We undertook to consider the interaction between genetic factors, including amyloid precursor protein (APP) and presenilin-1 (PS1), and environmental factors, such as Aluminum (Al) in determining susceptibility outcomes when studying the pathogenesis of AD. In this article, we provide an AD model in APP/PS1 transgenic mice triggered by Al. The animal model was established via intracerebral ventricular microinjection of aluminum chloride once a day for 5 days in APP/PS1 transgenic mice. Twenty wild type (WT) mice and 20 APP/PS1 transgenic (TG) mice were separately divided into 2 groups (control and Al group), and a stainless steel injector with stopper was used for microinjection into the left-lateral cerebral ventricle of each mouse. The Morris water maze task was used to evaluate behavioral function of learning and memory ability on the 20th day after the last injection. This AD model's brain was analyzed by: (1) amyloid beta immunohistochemical staining; (2) Tunnel staining; (3) apoptotic rates; (4) caspase-3 gene expression. Here, decrease of cognitive ability and neural cells loss were shown in APP/PS1 transgenic mice exposed to Al, which were more extensive than those in APP/PS1 TG alone and WT mice exposed to Al alone. These findings indicate that there is a close relationship between over-expression of APP and PS1 genes and Al overload. It is also suggested that APP/PS1 TG mice exposed to Al have potential value for improving AD models.

  15. Oxygen Uptake in Maximal Effort Constant Rate and Interval Running

    Directory of Open Access Journals (Sweden)

    Daniel Pratt

    2013-01-01

    Full Text Available This study investigated differences in average of maximal effort interval running to maximal effort constant rate running at lactate threshold matched for time. The average and distance covered of 10 recreational male runners (: 4158 ± 390 mL·min−1 were compared between a maximal effort constant-rate run at lactate threshold (CRLT, a maximal effort interval run (INT consisting of 2 min at speed with 2 minutes at 50% of repeated 5 times, and a run at the average speed sustained during the interval run (CR submax. Data are presented as mean and 95% confidence intervals. The average for INT, 3451 (3269–3633 mL·min−1, 83% , was not significantly different to CRLT, 3464 (3285–3643 mL·min−1, 84% , but both were significantly higher than CR sub-max, 3464 (3285–3643 mL·min−1, 76% . The distance covered was significantly greater in CLRT, 4431 (4202–3731 metres, compared to INT and CR sub-max, 4070 (3831–4309 metres. The novel finding was that a 20-minute maximal effort constant rate run uses similar amounts of oxygen as a 20-minute maximal effort interval run despite the greater distance covered in the maximal effort constant-rate run.

  16. The specific gamma-ray constant and exposure rate constant of 182Ta.

    Science.gov (United States)

    Glasgow, G P; Dillman, L T

    1982-01-01

    Reported values of the specific gamma-ray constant gamma for 182Ta range from the original value of 6.1 to 7.692 R cm2h-1mCi-1, recommended in NCRP Report No. 41. The original calculation of gamma was based on inadequate nuclear spectroscopy and decay scheme data. The higher value of gamma occurs because of a computational error in the relative intensity of the 1.2575-MeV gamma ray. Using nuclear spectroscopy data from the most recent Evaluated Nuclear Data File (ENSDF), gamma is calculated to be 6.71 +/- 0.06 R cm2h-1mCi-1 and the exposure rate constant gamma gamma is 6.87 +/- 0.06 R cm2h-1mCi-1. These new calculations are presented and previously reported values of gamma and gamma gamma are reviewed.

  17. Semiclassical Calculation of Reaction Rate Constants for Homolytical Dissociations

    Science.gov (United States)

    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.

  18. High-temperature rate constant measurements for OH+xylenes

    KAUST Repository

    Elwardani, Ahmed Elsaid

    2015-06-01

    The overall rate constants for the reactions of hydroxyl (OH) radicals with o-xylene (k 1), m-xylene (k 2), and p-xylene (k 3) were measured behind reflected shock waves over 890-1406K at pressures of 1.3-1.8atm using OH laser absorption near 306.7nm. Measurements were performed under pseudo-first-order conditions. The measured rate constants, inferred using a mechanism-fitting approach, can be expressed in Arrhenius form as:k1=2.93×1013exp(-1350.3/T)cm3mol-1s-1(890-1406K)k2=3.49×1013exp(-1449.3/T)cm3mol-1s-1(906-1391K)k3=3.5×1013exp(-1407.5/T)cm3mol-1s-1(908-1383K)This paper presents, to our knowledge, first high-temperature measurements of the rate constants of the reactions of xylene isomers with OH radicals. Low-temperature rate-constant measurements by Nicovich et al. (1981) were combined with the measurements in this study to obtain the following Arrhenius expressions, which are applicable over a wider temperature range:k1=2.64×1013exp(-1181.5/T)cm3mol-1s-1(508-1406K)k2=3.05×109exp(-400/T)cm3mol-1s-1(508-1391K)k3=3.0×109exp(-440/T)cm3mol-1s-1(526-1383K) © 2015 The Combustion Institute.

  19. Assessment of the analgesic potency of constant rate infusion of ...

    African Journals Online (AJOL)

    In this study, the analgesic potency of constant rate infusion of tramadol hydrochloride and as adjunct to ketoprofen on laparotomy-induced pain was evaluated. Dogs were randomly assigned to 4 groups (n=5). Groups 1, 2 and 3 received 0.5mg/kg/hr, 1.0mg/kg/hr and 2.0mg/kg/hr IV; CRI of tramadol hydrochloride ...

  20. Reaction Rate Constant for Radiative Association of CF$^+$

    CERN Document Server

    Öström, Jonatan; Nyman, Gunnar; Gustafsson, Magnus

    2015-01-01

    Reaction rate constants and cross sections are computed for the radiative association of carbon cations ($\\text{C}^+$) and fluorine atoms ($\\text{F}$) in their ground states. We consider reactions through the electronic transition $1^1\\Pi \\rightarrow X^1\\Sigma^+$ and rovibrational transitions on the $X^1\\Sigma^+$ and $a^3\\Pi$ potentials. Semiclassical and classical methods are used for the direct contribution and Breit--Wigner theory for the resonance contribution. Quantum mechanical perturbation theory is used for comparison. A modified formulation of the classical method applicable to permanent dipoles of unequally charged reactants is implemented. The total rate constant is fitted to the Arrhenius--Kooij formula in five temperature intervals with a relative difference of $<3\\:\\%$. The fit parameters will be added to the online database KIDA. For a temperature of $10$ to $250\\:\\text{K}$, the rate constant is about $10^{-21}\\:\\text{cm}^3\\text{s}^{-1}$, rising toward $10^{-16}\\:\\text{cm}^3\\text{s}^{-1}$ fo...

  1. Uniaxial tension test on Rubber at constant true strain rate

    Directory of Open Access Journals (Sweden)

    Sourne H.L.

    2012-08-01

    Full Text Available Elastomers are widely used for damping parts in different industrial contexts because of their remarkable dissipation properties. Indeed, they can undergo severe mechanical loading conditions, i.e., high strain rates and large strains. Nevertheless, the mechanical response of these materials can vary from purely rubber-like to glassy depending on the strain rate undergone. Classically, uniaxial tension tests are made in order to find a relation between the stress and the strain in the material at various strain rates. However, even if the strain rate is searched to be constant, it is the nominal strain rate that is considered. Here we develop a test at constant true strain rate, i.e. the strain rate that is experienced by the material. In order to do such a test, the displacement imposed by the machine is an exponential function of time. This test has been performed with a high speed hydraulic machine for strain rates between 0.01/s and 100/s. A specific specimen has been designed, yielding a uniform strain field (and so a uniform stress field. Furthermore, an instrumented aluminum bar has been used to take into account dynamic effects in the measurement of the applied force. A high speed camera enables the determination of strain in the sample using point tracking technique. Using this method, the stress-strain curve of a rubber-like material during a loading-unloading cycle has been determined, up to a stretch ratio λ = 2.5. The influence of the true strain rate both on stiffness and on dissipation of the material is then discussed.

  2. Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

    Science.gov (United States)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

    2008-01-01

    The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

  3. Specific gamma-ray constant and exposure rate constant of 192Ir.

    Science.gov (United States)

    Glasgow, G P; Dillman, L T

    1979-01-01

    Calculated values of the 192Ir specific gamma-ray constant, Gamma range from the low value of 3.948 R cm2h-1mCi-1 recommended in NCRP No. 41 to a high of 4.89 R cm2h-1mCi-1. Measured values of Gamma range only from 4.85 to 5.0 Rcm2h-1mCi-1. Discrepancies in reported calculated values exist because the isotope decay scheme and other nuclear spectroscopy data pertinent to these calculations were not well known. Using the 28 gamma rays and relative intensities from the most recent Evaluated Nuclear Structure Data File (ENSDF), Gamma is calculated to be 4.62 +/- 0.05 Rcm2h-1mCi-1 and the exposure rate constant Gamma delta is 4.69 +/- 0.05 Rcm2h-1mCi-1. These new calculations are presented and previously reported values of Gamma and Gamma delta are reviewed.

  4. Empirical correlation for prediction of the elutriation rate constant

    Directory of Open Access Journals (Sweden)

    Stojkovski Valentino

    2003-01-01

    Full Text Available In vessels containing fluidized solids, the gas leaving carries some suspended particles. This flux of solids is called entrainment, E or carryover and the bulk density of solids on this leaving gas stream is called the holdup. For design we need to know the rate of this entrainment and the size distribution of these entrained particles Rim in relation to the size distribution in the bed, Rib, as well as the variation of both these quantities with gas and solids properties, gas flow rate, bed geometry and location of the leaving gas stream. Steady-state elutriation experiments have been done in a fluidized bed 0,2 m diameter by 2,94 m high freeboard with superficial gas velocities up to 1 m/s using solids ranging in mean size from 0,15 to 0,58 mm and with particle density 2660 kg/m3. When the fine and coarse particles were mixed, the total entrainment flux above the freeboard was increased. None of the published correlations for estimating the elutriation rate constant were useful. A new simple equation, which is developed on the base of experimental results and theory of dimensional analyses, is presented.

  5. Measurement of both the equilibrium constant and rate constant for electronic energy transfer by control of the limiting kinetic regimes.

    Science.gov (United States)

    Vagnini, Michael T; Rutledge, W Caleb; Wagenknecht, Paul S

    2010-02-01

    Electronic energy transfer can fall into two limiting cases. When the rate of the energy transfer back reaction is much faster than relaxation of the acceptor excited state, equilibrium between the donor and acceptor excited states is achieved and only the equilibrium constant for the energy transfer can be measured. When the rate of the back reaction is much slower than relaxation of the acceptor, the energy transfer is irreversible and only the forward rate constant can be measured. Herein, we demonstrate that with trans-[Cr(d(4)-cyclam)(CN)(2)](+) as the donor and either trans-[Cr([15]ane-ane-N(4))(CN)(2)](+) or trans-[Cr(cyclam)(CN)(2)](+) as the acceptor, both limits can be obtained by control of the donor concentration. The equilibrium constant and rate constant for the case in which trans-[Cr([15]ane-ane-N(4))(CN)(2)](+) is the acceptor are 0.66 and 1.7 x 10(7) M(-1) s(-1), respectively. The equilibrium constant is in good agreement with the value of 0.60 determined using the excited state energy gap between the donor and acceptor species. For the thermoneutral case in which trans-[Cr(cyclam)(CN)(2)](+) is the acceptor, an experimental equilibrium constant of 0.99 was reported previously, and the rate constant has now been measured as 4.0 x 10(7) M(-1) s(-1).

  6. High-Temperature Slow Crack Growth of Silicon Carbide Determined by Constant-Stress-Rate and Constant-Stress Testing

    Science.gov (United States)

    Choi, Sung H.; Salem, J. A.; Nemeth, N. N.

    1998-01-01

    High-temperature slow-crack-growth behaviour of hot-pressed silicon carbide was determined using both constant-stress-rate ("dynamic fatigue") and constant-stress ("static fatigue") testing in flexure at 1300 C in air. Slow crack growth was found to be a governing mechanism associated with failure of the material. Four estimation methods such as the individual data, the Weibull median, the arithmetic mean and the median deviation methods were used to determine the slow crack growth parameters. The four estimation methods were in good agreement for the constant-stress-rate testing with a small variation in the slow-crack-growth parameter, n, ranging from 28 to 36. By contrast, the variation in n between the four estimation methods was significant in the constant-stress testing with a somewhat wide range of n= 16 to 32.

  7. Biodegradation testing of chemicals with high Henry’s constants – separating mass and effective concentration reveals higher rate constants

    DEFF Research Database (Denmark)

    Birch, Heidi; Andersen, Henrik Rasmus; Comber, Mike

    During simulation-type biodegradation tests, volatile chemicals will continuously partition between water phase and headspace. This study addressed how (1) this partitioning affects biodegradation test results and (2) it can be accounted for by combining mass balance and dynamic biodegradation...... Microextraction (HS-SPME) was applied directly on the test systems to measure substrate depletion by biodegradation relative to abiotic controls. HS-SPME was also applied to determine air to water partitioning ratios. Water phase biodegradation rate constants, kwater, were up to 72 times higher than test system...... biodegradation rate constants, ksystem. True water phase degradation rate constants facilitate extrapolation to other air-water systems and are more suitable input parameters for aquatic exposure and fate models. As such, they should be considered more appropriate for risk assessments than test system rate...

  8. Estimating hydraulic properties of volcanic aquifers using constant-rate and variable-rate aquifer tests

    Science.gov (United States)

    Rotzoll, K.; El-Kadi, A. I.; Gingerich, S.B.

    2007-01-01

    In recent years the ground-water demand of the population of the island of Maui, Hawaii, has significantly increased. To ensure prudent management of the ground-water resources, an improved understanding of ground-water flow systems is needed. At present, large-scale estimations of aquifer properties are lacking for Maui. Seven analytical methods using constant-rate and variable-rate withdrawals for single wells provide an estimate of hydraulic conductivity and transmissivity for 103 wells in central Maui. Methods based on constant-rate tests, although not widely used on Maui, offer reasonable estimates. Step-drawdown tests, which are more abundantly used than other tests, provide similar estimates as constant-rate tests. A numerical model validates the suitability of analytical solutions for step-drawdown tests and additionally provides an estimate of storage parameters. The results show that hydraulic conductivity is log-normally distributed and that for dike-free volcanic rocks it ranges over several orders of magnitude from 1 to 2,500 m/d. The arithmetic mean, geometric mean, and median values of hydraulic conductivity are respectively 520, 280, and 370 m/d for basalt and 80, 50, and 30 m/d for sediment. A geostatistical approach using ordinary kriging yields a prediction of hydraulic conductivity on a larger scale. Overall, the results are in agreement with values published for other Hawaiian islands. ?? 2007 American Water Resources Association.

  9. A Novel Rate Control Scheme for Constant Bit Rate Video Streaming

    Directory of Open Access Journals (Sweden)

    Venkata Phani Kumar M

    2015-08-01

    Full Text Available In this paper, a novel rate control mechanism is proposed for constant bit rate video streaming. The initial quantization parameter used for encoding a video sequence is determined using the average spatio-temporal complexity of the sequence, its resolution and the target bit rate. Simple linear estimation models are then used to predict the number of bits that would be necessary to encode a frame for a given complexity and quantization parameter. The experimental results demonstrate that our proposed rate control mechanism significantly outperforms the existing rate control scheme in the Joint Model (JM reference software in terms of Peak Signal to Noise Ratio (PSNR and consistent perceptual visual quality while achieving the target bit rate. Furthermore, the proposed scheme is validated through implementation on a miniature test-bed.

  10. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity extraction.

    Science.gov (United States)

    Zheng, Xiwei; Li, Zhao; Podariu, Maria I; Hage, David S

    2014-07-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug-protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug-protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies.

  11. Exergy analysis of integrated photovoltaic thermal solar water heater under constant flow rate and constant collection temperature modes

    NARCIS (Netherlands)

    Tiwari, A.; Dubey, Swapnil; Sandhu, G.S.; Sodha, M.S.; Anwar, S.I.

    2009-01-01

    In this communication, an analytical expression for the water temperature of an integrated photovoltaic thermal solar (IPVTS) water heater under constant flow rate hot water withdrawal has been obtained. Analysis is based on basic energy balance for hybrid flat plate collector and storage tank,

  12. Reaction rate constants of HO2 + O3 in the temperature range 233-400 K

    Science.gov (United States)

    Wang, Xiuyan; Suto, Masako; Lee, L. C.

    1988-01-01

    The reaction rate constants of HO2 + O3 were measured in the temperature range 233-400 K using a discharge flow system with photofragment emission detection. In the range 233-253 K, the constants are approximately a constant value, and then increase with increasing temperature. This result suggests that the reaction may have two different channels. An expression representing the reaction rate constants is presented.

  13. Universality of thermodynamic constants governing biological growth rates.

    Science.gov (United States)

    Corkrey, Ross; Olley, June; Ratkowsky, David; McMeekin, Tom; Ross, Tom

    2012-01-01

    Mathematical models exist that quantify the effect of temperature on poikilotherm growth rate. One family of such models assumes a single rate-limiting 'master reaction' using terms describing the temperature-dependent denaturation of the reaction's enzyme. We consider whether such a model can describe growth in each domain of life. A new model based on this assumption and using a hierarchical Bayesian approach fits simultaneously 95 data sets for temperature-related growth rates of diverse microorganisms from all three domains of life, Bacteria, Archaea and Eukarya. Remarkably, the model produces credible estimates of fundamental thermodynamic parameters describing protein thermal stability predicted over 20 years ago. The analysis lends support to the concept of universal thermodynamic limits to microbial growth rate dictated by protein thermal stability that in turn govern biological rates. This suggests that the thermal stability of proteins is a unifying property in the evolution and adaptation of life on earth. The fundamental nature of this conclusion has importance for many fields of study including microbiology, protein chemistry, thermal biology, and ecological theory including, for example, the influence of the vast microbial biomass and activity in the biosphere that is poorly described in current climate models.

  14. Universality of thermodynamic constants governing biological growth rates.

    Directory of Open Access Journals (Sweden)

    Ross Corkrey

    Full Text Available BACKGROUND: Mathematical models exist that quantify the effect of temperature on poikilotherm growth rate. One family of such models assumes a single rate-limiting 'master reaction' using terms describing the temperature-dependent denaturation of the reaction's enzyme. We consider whether such a model can describe growth in each domain of life. METHODOLOGY/PRINCIPAL FINDINGS: A new model based on this assumption and using a hierarchical Bayesian approach fits simultaneously 95 data sets for temperature-related growth rates of diverse microorganisms from all three domains of life, Bacteria, Archaea and Eukarya. Remarkably, the model produces credible estimates of fundamental thermodynamic parameters describing protein thermal stability predicted over 20 years ago. CONCLUSIONS/SIGNIFICANCE: The analysis lends support to the concept of universal thermodynamic limits to microbial growth rate dictated by protein thermal stability that in turn govern biological rates. This suggests that the thermal stability of proteins is a unifying property in the evolution and adaptation of life on earth. The fundamental nature of this conclusion has importance for many fields of study including microbiology, protein chemistry, thermal biology, and ecological theory including, for example, the influence of the vast microbial biomass and activity in the biosphere that is poorly described in current climate models.

  15. Iterative rate-distortion optimization of H.264 with constant bit rate constraint.

    Science.gov (United States)

    An, Cheolhong; Nguyen, Truong Q

    2008-09-01

    In this paper, we apply the primal-dual decomposition and subgradient projection methods to solve the rate-distortion optimization problem with the constant bit rate constraint. The primal decomposition method enables spatial or temporal prediction dependency within a group of picture (GOP) to be processed in the master primal problem. As a result, we can apply the dual decomposition to minimize independently the Lagrangian cost of all the MBs using the reference software model of H.264. Furthermore, the optimal Lagrange multiplier lambda* is iteratively derived from the solution of the dual problem. As an example, we derive the optimal bit allocation condition with the consideration of temporal prediction dependency among the pictures. Experimental results show that the proposed method achieves better performance than the reference software model of H.264 with rate control.

  16. The effect of temperature fluctuations of reaction rate constants in turbulent reacting flows

    Science.gov (United States)

    Chinitz, W.; Antaki, P. J.; Kassar, G. M.

    1981-01-01

    Current models of turbulent reacting flows frequently use Arrhenius reaction rate constants obtained from static or laminar flow theory and/or experiments, or from best fits of static, laminar, and turbulent data. By treating the reaction rate constant as a continuous random variable which is temperature-dependent, the present study assesses the effect of turbulent temperature fluctuations on the reaction rate constant. This model requires that a probability density function (PDF) describing the nature of the fluctuations be specified. Three PDFs are examined: the clipped Gaussian, the beta PDF, and the ramp model. All the models indicate that the reaction rate constant is greater in a turbulent flow field than in an equivalent laminar flow. In addition, an amplification ratio, which is the ratio of the turbulent rate constant to the laminar rate constant, is defined and its behavior as a function of the mean temperature fluctuations is described

  17. A model for turbulent dissipation rate in a constant pressure ...

    Indian Academy of Sciences (India)

    J Dey

    which is a good approximation in the log-layer [1, 3], urms is the characteristic velocity scale [4]. The inclusion of urms in this model is for this reason. Since рuurmsЮ1=2 $ OрusЮ in the log-layer, the proposed model for the dissipation rate in. Eq. (5) preserves the essence of Eqs. (1) or (4). At the boundary layer edge, y ! d ...

  18. Rate constants of reactions of {kappa}-carrageenan with hydrated electron and hydroxyl radical

    Energy Technology Data Exchange (ETDEWEB)

    Abad, L.V. [Nuclear Professional School, School of Engineering Laboratory, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines)], E-mail: lvabad@pnri.dost.gov.ph; Saiki, S.; Kudo, H.; Muroya, Y.; Katsumura, Y. [Nuclear Professional School, School of Engineering Laboratory, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Rosa, A.M. de la [Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines)

    2007-12-15

    The rate constants for the reactions of {kappa}-carrageenan with hydrated electron and hydroxyl radical was investigated by pulse radiolysis and laser photolysis. The kinetics of the reaction of hydrated electron indicates no seeming reaction with {kappa}-carrageenan. On the other hand, hydroxyl radical reacts very rapidly with {kappa}-carrageenan at a rate constant of approximately 1.2 x 10{sup 9} M{sup -1} s{sup -1}. This rate constant varies with pH.

  19. Measuring kinetic rate constants of multiple-component reactions with optical biosensors.

    Science.gov (United States)

    Edwards, David A; Evans, Ryan M; Li, Wenbin

    2017-09-15

    One may measure the kinetic rate constants associated with biochemical reactions using an optical biosensor: an instrument in which ligand molecules are convected through a flow cell over a surface to which receptors are immobilized. If there are multiple reactants, one is faced with the problem of fitting multiple kinetic rate constants to one signal, since data from all of the reacting species is lumped together. Even in the presence of ambiguous data, one may use a series of experiments to accurately determine the rate constants. Moreover, the true set of rate constants may be identified by either postprocessing the signals or adjusting the ligand inflow concentrations. Published by Elsevier Inc.

  20. Constrained least squares methods for estimating reaction rate constants from spectroscopic data

    NARCIS (Netherlands)

    Bijlsma, S.; Boelens, H. F. M.; Hoefsloot, H. C. J.; Smilde, A. K.

    2002-01-01

    Model errors, experimental errors and instrumental noise influence the accuracy of reaction rate constant estimates obtained from spectral data recorded in time during a chemical reaction. In order to improve the accuracy, which can be divided into the precision and bias of reaction rate constant

  1. Estimating reaction rate constants: comparison between traditional curve fitting and curve resolution

    NARCIS (Netherlands)

    Bijlsma, S.; Boelens, H. F. M.; Hoefsloot, H. C. J.; Smilde, A. K.

    2000-01-01

    A traditional curve fitting (TCF) algorithm is compared with a classical curve resolution (CCR) approach for estimating reaction rate constants from spectral data obtained in time of a chemical reaction. In the TCF algorithm, reaction rate constants an estimated from the absorbance versus time data

  2. Neural estimation of kinetic rate constants from dynamic PET-scans

    DEFF Research Database (Denmark)

    Fog, Torben L.; Nielsen, Lars Hupfeldt; Hansen, Lars Kai

    1994-01-01

    A feedforward neural net is trained to invert a simple three compartment model describing the tracer kinetics involved in the metabolism of [18F]fluorodeoxyglucose in the human brain. The network can estimate rate constants from positron emission tomography sequences and is about 50 times faster...... than direct fitting of rate constants using the parametrized transients of the compartment model...

  3. Low-energy electron impact cross-sections and rate constants of

    Indian Academy of Sciences (India)

    Anand Bharadvaja

    2017-07-24

    Jul 24, 2017 ... biological processes [2], modelling of combustion phe- nomenon [3,4] etc. The e. −−NH2 collision ..... pole extracted adiabatic nuclei (MEAN) method [53] is used to obtain the DCS. The methodology is .... effects. 2.3 Rate constants. The rate constants for any given process is given by [55] k(Te) = (. 2 me. ) ...

  4. Rate constants for the reaction of OH radicals with 1-chloroalkanes at 295 K

    DEFF Research Database (Denmark)

    Markert, F.; Nielsen, O.J.

    1992-01-01

    The rate constants for the reaction of OH radicals with a series of 1-chloroalkanes were measured at 295 K and at a total pressure of 1 atm. The rate constants were obtained by using the absolute technique of pulse radiolysis combined with kinetic UV-spectroscopy. The results are discussed in terms...

  5. On the ergodicity bounds for a constant retrial rate queueing model

    OpenAIRE

    Zeifman, Alexander; Satin, Yacov; Morozov, Evsey; Nekrasova, Ruslana; Gorshenin, Andrey

    2015-01-01

    We consider a Markovian single-server retrial queueing system with a constant retrial rate. Conditions of null ergodicity and exponential ergodicity for the correspondent process, as well as bounds on the rate of convergence are obtained.

  6. Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K/Akt pathway in the brain of APP/PS1 transgenic mouse.

    Science.gov (United States)

    He, Xuan-Li; Yan, Ning; Chen, Xiao-Shan; Qi, Yun-Wen; Yan, Yong; Cai, Zhiyou

    2016-10-01

    Endogenous hydrogen sulfide (H2S) may have multiple physiological functions in brain. Our previous study showed that H2S improved spatial memory impairment and decreased the production of Aβ in APP/PS1 transgenic mice. However, many of the underlying mechanisms are not still being elucidated. The aim of the present study is to investigate the neuroprotective mechanisms of H2S involving in the activity of β-secretase (BACE1), γ-secretase (PS1) and α-secretase (ADAM17). Morris water maze was used to measure the behavior change. The levels of Aβ40 and Aβ42 were quantified using colorimetric ELISA kits and immunohistochemical analysis. The levels of BACE1, PS1, ADAM17, pAkt, pp38MAPK, pERK and pJNK were tested by Western blot analysis in normal mice, APP/PS1 transgenic mice and 50μmol/kg-NaHS-treated transgenic mice. On the basis of exogenous H2S treatment, LY294002 (inhibitors of PI3K/Akt) or PD98059 (inhibitors of MAPK/ERK) was injected into lateral cerebral ventricle. The levels of BACE1, PS1 and pp38MAPK were increased and ADAM17 were decreased in the APP/PS1 transgenic mice. After intraperitoneal administration of an H2S donor (NaHS) into APP/PS1 mice, the levels of BACE1, PS1 and pp38MAPK were reduced and ADAM17 increased. The level of pp38 MAPKs, pAkt and pERK1/2 was increased in APP/PS1 transgenic mice compared with normal mice (ptransgenic mice and normal mice (p>0.05). These results demonstrated that LY294002 inhibited the effect of H2S on decreasing the BACE1 and PS1, reducing the level of Aβ and improving memory impairment in APP/PS1 transgenic mice. PD98059 had no influence on the expression of BACE1 and PS1. H2S inhibits the expression of BACE1 and PS1 by activating PI3K/Akt pathway in AD. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Development of a group contribution method to predict aqueous phase hydroxyl radical (HO*) reaction rate constants.

    Science.gov (United States)

    Minakata, Daisuke; Li, Ke; Westerhoff, Paul; Crittenden, John

    2009-08-15

    The hydroxyl radical (HO*) is a strong oxidant that reacts with electron-rich sites of organic compounds and initiates complex chain mechanisms. In order to help understand the reaction mechanisms, a rule-based model was previously developed to predict the reaction pathways. For a kinetic model, there is a need to develop a rate constant estimator that predicts the rate constants for a variety of organic compounds. In this study, a group contribution method (GCM) is developed to predict the aqueous phase HO* rate constants for the following reaction mechanisms: (1) H-atom abstraction, (2) HO* addition to alkenes, (3) HO* addition to aromatic compounds, and (4) HO* interaction with sulfur (S)-, nitrogen (N)-, or phosphorus (P)-atom-containing compounds. The GCM hypothesizes that an observed experimental rate constant for a given organic compound is the combined rate of all elementary reactions involving HO*, which can be estimated using the Arrhenius activation energy, E(a), and temperature. Each E(a) for those elementary reactions can be comprised of two parts: (1) a base part that includes a reactive bond in each reaction mechanism and (2) contributions from its neighboring functional groups. The GCM includes 66 group rate constants and 80 group contribution factors, which characterize each HO* reaction mechanism with steric effects of the chemical structure groups and impacts of the neighboring functional groups, respectively. Literature-reported experimental HO* rate constants for 310 and 124 compounds were used for calibration and prediction, respectively. The genetic algorithms were used to determine the group rate constants and group contribution factors. The group contribution factors for H-atom abstraction and HO* addition to the aromatic compounds were found to linearly correlate with the Taft constants, sigma*, and electrophilic substituent parameters, sigma+, respectively. The best calibrations for 83% (257 rate constants) and predictions for 62% (77

  8. Potential energy construction in the diabatic picture for quantum mechanical rate constants of intermolecular proton transfer.

    Science.gov (United States)

    Hori, Yuta; Ida, Tomonori; Mizuno, Motohiro

    2017-06-28

    We propose a simple method for potential construction in the diabatic picture and the estimation of thermal rate constants for intermolecular proton transfer reactions using quantum dynamics simulations carried out on the constructed potentials. For symmetrical and asymmetrical proton transfer pairs, the obtained potentials and rate constants were in good agreement with the reference values. Furthermore, our method is used for the analysis of proton transfer in crystalline imidazolium succinate and discusses the proton conductivity in terms of intermolecular proton transfer. This approach can be used to estimate proton transfer rate constants for large molecular systems, even when the calculation of the transition state is impossible.

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

    Energy Technology Data Exchange (ETDEWEB)

    Osborne, David; Lawson, Patrick; Adams, Nigel, E-mail: ngadams@uga.edu [University of Georgia, Department of Chemistry, 101 Cedar St., Athens, Georgia 30602 (United States)

    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.

  10. Impact of uncertainties in inorganic chemical rate constants on tropospheric composition and ozone radiative forcing

    Science.gov (United States)

    Newsome, Ben; Evans, Mat

    2017-12-01

    Chemical rate constants determine the composition of the atmosphere and how this composition has changed over time. They are central to our understanding of climate change and air quality degradation. Atmospheric chemistry models, whether online or offline, box, regional or global, use these rate constants. Expert panels evaluate laboratory measurements, making recommendations for the rate constants that should be used. This results in very similar or identical rate constants being used by all models. The inherent uncertainties in these recommendations are, in general, therefore ignored. We explore the impact of these uncertainties on the composition of the troposphere using the GEOS-Chem chemistry transport model. Based on the Jet Propulsion Laboratory (JPL) and International Union of Pure and Applied Chemistry (IUPAC) evaluations we assess the influence of 50 mainly inorganic rate constants and 10 photolysis rates on tropospheric composition through the use of the GEOS-Chem chemistry transport model. We assess the impact on four standard metrics: annual mean tropospheric ozone burden, surface ozone and tropospheric OH concentrations, and tropospheric methane lifetime. Uncertainty in the rate constants for NO2 + OH →M HNO3 and O3 + NO → NO2 + O2 are the two largest sources of uncertainty in these metrics. The absolute magnitude of the change in the metrics is similar if rate constants are increased or decreased by their σ values. We investigate two methods of assessing these uncertainties, addition in quadrature and a Monte Carlo approach, and conclude they give similar outcomes. Combining the uncertainties across the 60 reactions gives overall uncertainties on the annual mean tropospheric ozone burden, surface ozone and tropospheric OH concentrations, and tropospheric methane lifetime of 10, 11, 16 and 16 %, respectively. These are larger than the spread between models in recent model intercomparisons. Remote regions such as the tropics, poles and upper

  11. A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion

    OpenAIRE

    Yu, Rui-hong; Cao, Yong-Xiao

    2017-01-01

    On account of the disturbance from the distribution phase, the concentration-time curve of drugs cannot fully reflect the characteristics of elimination, and thus, it is difficult for present methods to obtain ideal pharmacokinetic parameters. This paper presents a method to determine pharmacokinetic parameters based on an andante constant-rate intravenous infusion. A mathematical model of the constant-rate intravenous infusion combined with the elimination of first-order kinetics was establi...

  12. Determination of rapid chlorination rate constants by a stopped-flow spectrophotometric competition kinetics method.

    Science.gov (United States)

    Song, Dean; Liu, Huijuan; Qiang, Zhimin; Qu, Jiuhui

    2014-05-15

    Free chlorine is extensively used for water and wastewater disinfection nowadays. However, it still remains a big challenge to determine the rate constants of rapid chlorination reactions although competition kinetics and stopped-flow spectrophotometric (SFS) methods have been employed individually to investigate fast reaction kinetics. In this work, we proposed an SFS competition kinetics method to determine the rapid chlorination rate constants by using a common colorimetric reagent, N,N-diethyl-p-phenylenediamine (DPD), as a reference probe. A kinetic equation was first derived to estimate the reaction rate constant of DPD towards chlorine under a given pH and temperature condition. Then, on that basis, an SFS competition kinetics method was proposed to determine directly the chlorination rate constants of several representative compounds including tetracycline, ammonia, and four α-amino acids. Although Cl2O is more reactive than HOCl, its contribution to the overall chlorination kinetics of the test compounds could be neglected in this study. Finally, the developed method was validated through comparing the experimentally measured chlorination rate constants of the selected compounds with those obtained or calculated from literature and analyzing with Taft's correlation as well. This study demonstrates that the SFS competition kinetics method can measure the chlorination rate constants of a test compound rapidly and accurately. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

    Science.gov (United States)

    Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

    2017-10-01

    During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017

  14. Systematic Angle Random Walk Estimation of the Constant Rate Biased Ring Laser Gyro

    Directory of Open Access Journals (Sweden)

    Guohu Feng

    2013-02-01

    Full Text Available An actual account of the angle random walk (ARW coefficients of gyros in the constant rate biased rate ring laser gyro (RLG inertial navigation system (INS is very important in practical engineering applications. However, no reported experimental work has dealt with the issue of characterizing the ARW of the constant rate biased RLG in the INS. To avoid the need for high cost precise calibration tables and complex measuring set-ups, the objective of this study is to present a cost-effective experimental approach to characterize the ARW of the gyros in the constant rate biased RLG INS. In the system, turntable dynamics and other external noises would inevitably contaminate the measured RLG data, leading to the question of isolation of such disturbances. A practical observation model of the gyros in the constant rate biased RLG INS was discussed, and an experimental method based on the fast orthogonal search (FOS for the practical observation model to separate ARW error from the RLG measured data was proposed. Validity of the FOS-based method was checked by estimating the ARW coefficients of the mechanically dithered RLG under stationary and turntable rotation conditions. By utilizing the FOS-based method, the average ARW coefficient of the constant rate biased RLG in the postulate system is estimated. The experimental results show that the FOS-based method can achieve high denoising ability. This method estimate the ARW coefficients of the constant rate biased RLG in the postulate system accurately. The FOS-based method does not need precise calibration table with high cost and complex measuring set-up, and Statistical results of the tests will provide us references in engineering application of the constant rate biased RLG INS.

  15. Reaction rate constants of H-abstraction by OH from large ketones: measurements and site-specific rate rules.

    Science.gov (United States)

    Badra, Jihad; Elwardany, Ahmed E; Farooq, Aamir

    2014-06-28

    Reaction rate constants of the reaction of four large ketones with hydroxyl (OH) are investigated behind reflected shock waves using OH laser absorption. The studied ketones are isomers of hexanone and include 2-hexanone, 3-hexanone, 3-methyl-2-pentanone, and 4-methl-2-pentanone. Rate constants are measured under pseudo-first-order kinetics at temperatures ranging from 866 K to 1375 K and pressures near 1.5 atm. The reported high-temperature rate constant measurements are the first direct measurements for these ketones under combustion-relevant conditions. The effects of the position of the carbonyl group (C=O) and methyl (CH3) branching on the overall rate constant with OH are examined. Using previously published data, rate constant expressions covering, low-to-high temperatures, are developed for acetone, 2-butanone, 3-pentanone, and the hexanone isomers studied here. These Arrhenius expressions are used to devise rate rules for H-abstraction from various sites. Specifically, the current scheme is applied with good success to H-abstraction by OH from a series of n-ketones. Finally, general expressions for primary and secondary site-specific H-abstraction by OH from ketones are proposed as follows (the subscript numbers indicate the number of carbon atoms bonded to the next-nearest-neighbor carbon atom, the subscript CO indicates that the abstraction is from a site next to the carbonyl group (C=O), and the prime is used to differentiate different neighboring environments of a methylene group):

  16. Reaction mechanisms and rate constants of waste degradation in landfill bioreactor systems with enzymatic-enhancement.

    Science.gov (United States)

    Jayasinghe, P A; Hettiaratchi, J P A; Mehrotra, A K; Kumar, S

    2014-06-01

    Augmenting leachate before recirculation with peroxidase enzymes is a novel method to increase the available carbon, and therefore the food supply to microorganisms at the declining phase of the anaerobic landfill bioreactor operation. In order to optimize the enzyme-catalyzed leachate recirculation process, it is necessary to identify the reaction mechanisms and determine rate constants. This paper presents a kinetic model developed to ascertain the reaction mechanisms and determine the rate constants for enzyme catalyzed anaerobic waste degradation. The maximum rate of reaction (Vmax) for MnP enzyme-catalyzed reactors was 0.076 g(TOC)/g(DS).day. The catalytic turnover number (k(cat)) of the MnP enzyme-catalyzed was 506.7 per day while the rate constant (k) of the un-catalyzed reaction was 0.012 per day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Numerical methods for realizing nonstationary Poisson processes with piecewise-constant instantaneous-rate functions

    DEFF Research Database (Denmark)

    Harrod, Steven; Kelton, W. David

    2006-01-01

    with piecewise-constant instantaneous rate functions, a capability that has been implemented in commercial simulation software. They test these algorithms in C programs and make comparisons of accuracy, speed, and variability across disparate rate functions and microprocessor architectures. Choice of optimal...

  18. Constant specific growth rate in fed-batch cultivation of Bordetella pertussis using adaptive control

    NARCIS (Netherlands)

    Soons, Z.I.T.A.; Voogt, J.A.; Straten, van G.; Boxtel, van A.J.B.

    2006-01-01

    Monitoring and control of production processes for biopharmaceuticals have become standard requirements to support consistency and quality. In this paper, a constant specific growth rate in fed-batch cultivation of Bordetella pertussis is achieved by a newly designed specific growth rate controller.

  19. On the Values at Equilibrium and Rate Constants in Inter - Conversion Processes.

    Science.gov (United States)

    Olteanu, Octav

    2016-01-01

    Inter - conversion processes of labile molecules obey similar rules to those of reversible chemical reactions. Solving the corresponding linear differential systems is used along this work, as well as in the preceding version. The main purpose of the present mini revue paper is to recall, improve and correct some mathematical methods in determining the optimal values at equilibrium, and remarkable particular rate constants. This part was not proved correctly in my previous work. In my previous work, the proof of the equality of the concentrations of the main species at equilibrium was not correct. In the current manuscript, we use increasing velocity in order to obtain this first important result. To this aim, one applies Schwarz inequality and the case when equality occurs. In order to determine significant rate constants, we characterize these special values in terms of the norm of the linear operator defined by the matrix of the differential system. In my previous work, the normal probability density function was used. The latter method was not realistic. Increasing the velocity, one obtains equal optimal values of the concentrations at equilibrium. This method represents a patent in the field. Secondly, characterization of remarkable rate constants (which are also equal) is deduced. The optimal solutions are written explicitly. Under suitable conditions, the values at equilibrium and the rate constants are equal. The common value at equilibrium equals the common value of the rate constants.

  20. ARTICLE Predicting Rate Constants for Nucleophilic Reactions of Amines with Diarylcarbenium Ions Using an ONIOM Method

    Science.gov (United States)

    Zhang, Zhi-ping; Wang, Chen; Fu, Yao; Guo, Qing-xiang

    2010-12-01

    The rate constants of the nucleophilic reactions between amines and benzhydrylium ions were calculated using first-principles theoretical methods. Solvation models including PCM, CPCM, and COSMORS, as well as different types of atomic radii including UA0, UAKS, UAHF, Bondi, and UFF, and several single-point energy calculation methods (B3LYP, B3P86, B3PW91, BHANDH, PBEPBE, BMK, M06, MP2, and ONIOM method) were examined. By comparing the correlation between experimental rate constants and the calculated values, the ONIOM(CCSD(T)/6-311++G(2df,2p):B3LYP/6-311++G(2df,2p))// B3LYP/6-31G(d)/PCM/UFF) method was found to perform the best. This method was then employed to calculate the rate constants of the reactions between diverse amines and diarylcarbenium ions. The calculated rate constants for 65 reactions of amines with diarylcarbenium ions are in agreement with the experimental values, indicating that it is feasible to predict the rate constant of a reaction between an amine and a diarylcarbenium ion through ab initio calculation.

  1. Microscopic Rate Constants of Crystal Growth from Molecular Dynamic Simulations Combined with Metadynamics

    Directory of Open Access Journals (Sweden)

    Dániel Kozma

    2012-01-01

    Full Text Available Atomistic simulation of crystal growth can be decomposed into two steps: the determination of the microscopic rate constants and a mesoscopic kinetic Monte Carlo simulation. We proposed a method to determine kinetic rate constants of crystal growth. We performed classical molecular dynamics on the equilibrium liquid/crystal interface of argon. Metadynamics was used to explore the free energy surface of crystal growth. A crystalline atom was selected at the interface, and it was displaced to the liquid phase by adding repulsive Gaussian potentials. The activation free energy of this process was calculated as the maximal potential energy density of the Gaussian potentials. We calculated the rate constants at different interfacial structures using the transition state theory. In order to mimic real crystallization, we applied a temperature difference in the calculations of the two opposite rate constants, and they were applied in kinetic Monte Carlo simulation. The novelty of our technique is that it can be used for slow crystallization processes, while the simple following of trajectories can be applied only for fast reactions. Our method is a possibility for determination of elementary rate constants of crystal growth that seems to be necessary for the long-time goal of computer-aided crystal design.

  2. A new approach using coagulation rate constant for evaluation of turbidity removal

    Science.gov (United States)

    Al-Sameraiy, Mukheled

    2017-06-01

    Coagulation-flocculation-sedimentation processes for treating three levels of bentonite synthetic turbid water using date seeds (DS) and alum (A) coagulants were investigated in the previous research work. In the current research, the same experimental results were used to adopt a new approach on a basis of using coagulation rate constant as an investigating parameter to identify optimum doses of these coagulants. Moreover, the performance of these coagulants to meet (WHO) turbidity standard was assessed by introducing a new evaluating criterion in terms of critical coagulation rate constant (kc). Coagulation rate constants (k2) were mathematically calculated in second order form of coagulation process for each coagulant. The maximum (k2) values corresponded to doses, which were obviously to be considered as optimum doses. The proposed criterion to assess the performance of coagulation process of these coagulants was based on the mathematical representation of (WHO) turbidity guidelines in second order form of coagulation process stated that (k2) for each coagulant should be ≥ (kc) for each level of synthetic turbid water. For all tested turbid water, DS coagulant could not satisfy it. While, A coagulant could satisfy it. The results obtained in the present research are exactly in agreement with the previous published results in terms of finding optimum doses for each coagulant and assessing their performances. On the whole, it is recommended considering coagulation rate constant to be a new approach as an indicator for investigating optimum doses and critical coagulation rate constant to be a new evaluating criterion to assess coagulants' performance.

  3. Extraction of elementary rate constants from global network analysis of E. coli central metabolism

    Directory of Open Access Journals (Sweden)

    Broderick Gordon

    2008-05-01

    Full Text Available Abstract Background As computational performance steadily increases, so does interest in extending one-particle-per-molecule models to larger physiological problems. Such models however require elementary rate constants to calculate time-dependent rate coefficients under physiological conditions. Unfortunately, even when in vivo kinetic data is available, it is often in the form of aggregated rate laws (ARL that do not specify the required elementary rate constants corresponding to mass-action rate laws (MRL. There is therefore a need to develop a method which is capable of automatically transforming ARL kinetic information into more detailed MRL rate constants. Results By incorporating proteomic data related to enzyme abundance into an MRL modelling framework, here we present an efficient method operating at a global network level for extracting elementary rate constants from experiment-based aggregated rate law (ARL models. The method combines two techniques that can be used to overcome the difficult properties in parameterization. The first, a hybrid MRL/ARL modelling technique, is used to divide the parameter estimation problem into sub-problems, so that the parameters of the mass action rate laws for each enzyme are estimated in separate steps. This reduces the number of parameters that have to be optimized simultaneously. The second, a hybrid algebraic-numerical simulation and optimization approach, is used to render some rate constants identifiable, as well as to greatly narrow the bounds of the other rate constants that remain unidentifiable. This is done by incorporating equality constraints derived from the King-Altman and Cleland method into the simulated annealing algorithm. We apply these two techniques to estimate the rate constants of a model of E. coli glycolytic pathways. The simulation and statistical results show that our innovative method performs well in dealing with the issues of high computation cost, stiffness, local

  4. Apparent rate constant mapping using hyperpolarized [1-(13) C]pyruvate

    DEFF Research Database (Denmark)

    Khegai, O.; Schulte, R. F.; Janich, M. A.

    2014-01-01

    ) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build-up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies......-13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build-up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors......Hyperpolarization of [1-13C]pyruvate in solution allows real-time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate...

  5. Reaction rate constant of HO2+O3 measured by detecting HO2 from photofragment fluorescence

    Science.gov (United States)

    Manzanares, E. R.; Suto, Masako; Lee, Long C.; Coffey, Dewitt, Jr.

    1986-01-01

    A room-temperature discharge-flow system investigation of the rate constant for the reaction 'HO2 + O3 yields OH + 2O2' has detected HO2 through the OH(A-X) fluorescence produced by photodissociative excitation of HO2 at 147 nm. A reaction rate constant of 1.9 + or - 0.3 x 10 to the -15th cu cm/molecule per sec is obtained from first-order decay of HO2 in excess O3; this agrees well with published data.

  6. mineralization rate constants, half-lives and effects of two organic ...

    African Journals Online (AJOL)

    Total N (g/kg). 1.04. C:N ratio. 1.2. Table 2: Organic C and N contents of cattle dung and swine waste. Parameters. Cattle dung. Swine waste. Organic C (g/kg). Total N (g/kg). C: N ratio. 78.6. 14.6. 5:1. 68.4. 19.2. 3:1. Table 3: Mineralization rate constant and half life. Treatment. Minera. rate constant. Half-life (days). CD0SW0.

  7. An Empirical Rate Constant Based Model to Study Capacity Fading in Lithium Ion Batteries

    Directory of Open Access Journals (Sweden)

    Srivatsan Ramesh

    2015-01-01

    Full Text Available A one-dimensional model based on solvent diffusion and kinetics to study the formation of the SEI (solid electrolyte interphase layer and its impact on the capacity of a lithium ion battery is developed. The model uses the earlier work on silicon oxidation but studies the kinetic limitations of the SEI growth process. The rate constant of the SEI formation reaction at the anode is seen to play a major role in film formation. The kinetics of the reactions for capacity fading for various battery systems are studied and the rate constants are evaluated. The model is used to fit the capacity fade in different battery systems.

  8. Impact of uncertainties in inorganic chemical rate constants on tropospheric composition and ozone radiative forcing

    Directory of Open Access Journals (Sweden)

    B. Newsome

    2017-12-01

    Full Text Available Chemical rate constants determine the composition of the atmosphere and how this composition has changed over time. They are central to our understanding of climate change and air quality degradation. Atmospheric chemistry models, whether online or offline, box, regional or global, use these rate constants. Expert panels evaluate laboratory measurements, making recommendations for the rate constants that should be used. This results in very similar or identical rate constants being used by all models. The inherent uncertainties in these recommendations are, in general, therefore ignored. We explore the impact of these uncertainties on the composition of the troposphere using the GEOS-Chem chemistry transport model. Based on the Jet Propulsion Laboratory (JPL and International Union of Pure and Applied Chemistry (IUPAC evaluations we assess the influence of 50 mainly inorganic rate constants and 10 photolysis rates on tropospheric composition through the use of the GEOS-Chem chemistry transport model. We assess the impact on four standard metrics: annual mean tropospheric ozone burden, surface ozone and tropospheric OH concentrations, and tropospheric methane lifetime. Uncertainty in the rate constants for NO2 + OH →M  HNO3 and O3 + NO  →  NO2 + O2 are the two largest sources of uncertainty in these metrics. The absolute magnitude of the change in the metrics is similar if rate constants are increased or decreased by their σ values. We investigate two methods of assessing these uncertainties, addition in quadrature and a Monte Carlo approach, and conclude they give similar outcomes. Combining the uncertainties across the 60 reactions gives overall uncertainties on the annual mean tropospheric ozone burden, surface ozone and tropospheric OH concentrations, and tropospheric methane lifetime of 10, 11, 16 and 16 %, respectively. These are larger than the spread between models in recent model intercomparisons. Remote

  9. Simulation of a wide area survey for NEOs with Pan-STARRS PS1 & PS2 Telescopes

    Science.gov (United States)

    Chambers, Kenneth C.; Lilly (Schunova), Eva; Dukes, Martin Todd; Wainscoat, Richard J.

    2017-10-01

    We have performed a new survey simulation for a wide area survey with PS1 & PS2 as part of our quest to optimize the discovery rate of Near Earth Objects with the full Pan-STARRS system. The survey is intended to be as unbiased and as complete as possible given the available sky visibility and the anticipated performance of the PS1 and PS2 telescopes working together. The simulation includes a complete model of both telescopes, camera and slew overhead, sky visibility, moon phase, galactic plane exclusion, and weather. The performance of the resulting survey strategy is then evaluated using the method of Lilly et. al. 2017. This uses the Greenstreet et al. 2012 model with 50 million NEOs with absolute magnitudes 13 < H < 29 and the Moving Object Processing System (MOPS, Denneau et al. 2013) for linkages. The results are compared with other possible strategies.

  10. USE OF ROUGH SETS AND SPECTRAL DATA FOR BUILDING PREDICTIVE MODELS OF REACTION RATE CONSTANTS

    Science.gov (United States)

    A model for predicting the log of the rate constants for alkaline hydrolysis of organic esters has been developed with the use of gas-phase min-infrared library spectra and a rule-building software system based on the mathematical theory of rough sets. A diverse set of 41 esters ...

  11. Low-energy electron impact cross-sections and rate constants of NH2

    Indian Academy of Sciences (India)

    This systematic study reports various electron impact cross-sections, rate constants and transport properties of N H 2 radical in the low-energy limit. The collision study is based on R -matrix formalism and involves the use of various scattering models employing different active spaces. Both electron excited ...

  12. Theoretical and Shock Tube Study of the Rate Constants for Hydrogen Abstraction Reactions of Ethyl Formate

    KAUST Repository

    Wu, Junjun

    2017-08-03

    We report a systematic chemical kinetics study of the H-atom abstractions from ethyl formate (EF) by H, O(3P), CH3, OH, and HO2 radicals. The geometry optimization and frequency calculation of all the species were conducted using the M06 method and the cc-pVTZ basis set. The one-dimensional hindered rotor treatment of the reactants and transition states and the intrinsic reaction coordinate analysis were also performed at the M06/cc-pVTZ level of theory. The relative electronic energies were calculated at the CCSD(T)/cc-pVXZ (where X = D, T) level of theory and further extrapolated to the complete basis set limit. Rate constants for the tittle reactions were calculated over the temperature range of 500‒2500 K by the transition state theory (TST) in conjunction with asymmetric Eckart tunneling effect. In addition, the rate constants of H-abstraction by hydroxyl radical were measured in shock tube experiments at 900‒1321 K and 1.4‒2.0 atm. Our theoretical rate constants of OH + EF → Products agree well with the experimental results within 15% over the experimental temperature range of 900‒1321 K. Branching ratios for the five types of H-abstraction reactions were also determined from their individual site-specific rate constants.

  13. Numerical bifurcation of predator-prey fractional differential equations with a constant rate harvesting

    Energy Technology Data Exchange (ETDEWEB)

    Erjaee, G H [Mathematics and Physics Department, Qatar University, Doha (Qatar)], E-mail: erjaee@qu.edu.qa

    2008-02-15

    In this article saddle and Hopf bifurcation points of predator-prey fractional differential equations system with a constant rate harvesting are investigated. The numerical results based on Grunwald-Letnikov discretization for fractional differential equations together with the Mickens' non-standard discretization method agree with those found by the corresponding ordinary differential equation system.

  14. Numerical bifurcation of predator-prey fractional differential equations with a constant rate harvesting

    Science.gov (United States)

    Erjaee, G. H.

    2008-02-01

    In this article saddle and Hopf bifurcation points of predator-prey fractional differential equations system with a constant rate harvesting are investigated. The numerical results based on Grunwald-Letnikov discretization for fractional differential equations together with the Mickens' non-standard discretization method agree with those found by the corresponding ordinary differential equation system.

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

    Science.gov (United States)

    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 ...

  16. Constant Savings Rates and Quasi-arithmetic Population Growth under Exhaustible Resource Constraints

    NARCIS (Netherlands)

    Asheim, G.; Buchholz, W.; Hartwick, J.; Mitra, T.; Withagen, C.A.A.M.

    2007-01-01

    In the Dasgupta-Heal-Solow-Stiglitz (DHSS) model of capital accumulation and resource depletion we show the following equivalence: if an efficient path has constant (gross and net of population growth) savings rates, then population growth must be quasi-arithmetic and the path is a maximin or a

  17. Stress relaxation of entangled polystyrene solution after constant-rate, uniaxial elongation

    DEFF Research Database (Denmark)

    Matsumiya, Yumi; Masubuchi, Yuichi; Watanabe, Hiroshi

    For an entangled solution of linear polystyrene (PS 545k; M = 545k) in dibutyl phthalate (DBP), the stress relaxation after constant-rate uniaxial elongation was examined with an extensional viscosity fixture mounted on ARES (TA Instruments). The PS concentration, c = 52 wt%, was chosen in a way...

  18. Separating the effect of respiration from the heart rate variability for cases of constant harmonic breathing

    Directory of Open Access Journals (Sweden)

    Kircher Michael

    2015-09-01

    Full Text Available Heart Rate Variability studies are a known measure for the autonomous control of the heart rate. In special situations, its interpretation can be ambiguous, since the respiration has a major influence on the heart rate variability. For this reason it has often been proposed to measure Heart Rate Variability, while the subjects are breathing at a constant respiration rate. That way the spectral influence of the respiration is known. In this work we propose to remove this constant respiratory influence from the heart rate and the Heart Rate Variability parameters to gain respiration free autonomous controlled heart rate signal. The spectral respiratory component in the heart rate signal is detected and characterized. Subsequently the respiratory effect on Heart Rate Variability is removed using spectral filtering approaches, such as the Notch filter or the Raised Cosine filter. As a result new decoupled Heart Variability parameters are gained, which could lead to new additional interpretations of the autonomous control of the heart rate.

  19. Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice.

    Science.gov (United States)

    Couch, Brian A; Kerrisk, Meghan E; Kaufman, Adam C; Nygaard, Haakon B; Strittmatter, Stephen M; Koleske, Anthony J

    2013-04-15

    Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4-9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed AβPP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred AβPP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed AβPP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred AβPP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed AβPP/PS1 mice of the same age. Surprisingly, inbred AβPP/PS1 mice at 8 months have low plaque burden, suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of AβPP processing revealed that elevated levels of soluble Aβ correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and AβPP processing are sensitive to genetic differences between mouse strains. Copyright © 2012 Wiley Periodicals, Inc.

  20. Efficient quantum-classical method for computing thermal rate constant of recombination: application to ozone formation.

    Science.gov (United States)

    Ivanov, Mikhail V; Babikov, Dmitri

    2012-05-14

    Efficient method is proposed for computing thermal rate constant of recombination reaction that proceeds according to the energy transfer mechanism, when an energized molecule is formed from reactants first, and is stabilized later by collision with quencher. The mixed quantum-classical theory for the collisional energy transfer and the ro-vibrational energy flow [M. Ivanov and D. Babikov, J. Chem. Phys. 134, 144107 (2011)] is employed to treat the dynamics of molecule + quencher collision. Efficiency is achieved by sampling simultaneously (i) the thermal collision energy, (ii) the impact parameter, and (iii) the incident direction of quencher, as well as (iv) the rotational state of energized molecule. This approach is applied to calculate third-order rate constant of the recombination reaction that forms the (16)O(18)O(16)O isotopomer of ozone. Comparison of the predicted rate vs. experimental result is presented.

  1. Propargyl Recombination: Estimation of the High Temperature, Low Pressure Rate Constant from Flame Measurements

    DEFF Research Database (Denmark)

    Rasmussen, Christian Lund; Skjøth-Rasmussen, Martin Skov; Jensen, Anker

    2005-01-01

    The most important cyclization reaction in hydrocarbon flames is probably recombination of propargyl radicals. This reaction may, depending on reaction conditions, form benzene, phenyl or fulvene, as well as a range of linear products. A number of rate measurements have been reported for C3H3 + C3H......3 at temperatures below 1000 K, while data at high temperature and low pressure only can be obtained from flames. In the present work, an estimate of the rate constant for the reaction at 1400 +/- 50 K and 20 Torr is obtained from analysis of the fuel-rich acetylene flame of Westmoreland, Howard......, and Longwell. Based on an accurate modeling of the flame structure, in particular the concentration profile of propargyl, we estimate the rate constant by fitting the kinetic modeling predictions to the measured benzene and phenyl profiles. The best agreement is obtained with k = 1.3 x 10(12) cm(3)/mol...

  2. The Rate Constant for the Reaction H + C2H5 at T = 295 - 150K

    Science.gov (United States)

    Pimentel, Andre S.; Payne, Walter A.; Nesbitt, Fred L.; Cody, Regina J.; Stief, Louis J.

    2004-01-01

    The reaction between the hydrogen atom and the ethyl (C2H3) radical is predicted by photochemical modeling to be the most important loss process for C2H5 radicals in the atmospheres of Jupiter and Saturn. This reaction is also one of the major sources for the methyl radicals in these atmospheres. These two simplest hydrocarbon radicals are the initial species for the synthesis of larger hydrocarbons. Previous measurements of the rate constant for the H + C2H5 reaction varied by a factor of five at room temperature, and some studies showed a dependence upon temperature while others showed no such dependence. In addition, the previous studies were at higher temperatures and generally higher pressures than that needed for use in planetary atmospheric models. The rate constant for the reaction H + C2H5 has been measured directly at T = 150, 202 and 295 K and at P = 1.0 Torr He for all temperatures and additionally at P = 0.5 and 2.0 Torr He at T = 202 K. The measurements were performed in a discharge - fast flow system. The decay of the C2H5 radical in the presence of excess hydrogen was monitored by low-energy electron impact mass spectrometry under pseudo-first order conditions. H atoms and C2H5 radicals were generated rapidly and simultaneously by the reaction of fluorine atoms with H2 and C2H6, respectively. The total rate constant was found to be temperature and pressure independent. The measured total rate constant at each temperature are: k(sub 1)(295K) = (1.02+/-0.24)x10(exp -10), k(sub 1)(202K) = (1.02+/-0.22)x10(exp -10) and k(sub 1)(150K) = (0.93+/-0.21)x10(exp -10), all in units of cu cm/molecule/s. The total rate constant derived from all the combined measurements is k(sub 1) = (l.03+/-0.17)x10(exp -10) cu cm/molecule/s. At room temperature our results are about a factor of two higher than the recommended rate constant and a factor of three lower than the most recently published study.

  3. Rate constant for the reaction SO + BrO yields SO2 + Br

    Science.gov (United States)

    Brunning, J.; Stief, L.

    1986-01-01

    The rate of the radical-radical reaction SO + BrO yields SO2 + Br has been determined at 298 K in a discharge flow system near 1 torr pressure with detection of SO and BrO via collision-free sampling mass spectrometry. The rate constant was determined using two different methods: measuring the decay of SO radicals in the presence of an excess of BrO and measuring the decay of BrO radicals in excess SO. The results from the two methods are in reasonable agreement and the simple mean of the two values gives the recommended rate constant at 298 K, k = (5.7 + or - 2.0) x 10 to the -11th cu cm/s. This represents the first determination of this rate constant and it is consistent with a previously derived lower limit based on SO2 formation. Comparison is made with other radical-radical reactions involving SO or BrO. The reaction SO + BrO yields SO2 + Br is of interest for models of the upper atmosphere of the earth and provides a potential coupling between atmospheric sulfur and bromine chemistry.

  4. Low-Temperature Experimental and Theoretical Rate Constants for the O(1D) + H2Reaction.

    Science.gov (United States)

    Hickson, Kevin M; Suleimanov, Yury V

    2017-03-09

    In the present joint experimental and theoretical study, we report thermal rate constants for the O( 1 D) + H 2 reaction within the 50-300 K temperature range. Experimental kinetics measurements were performed using a continuous supersonic flow reactor coupled with pulsed laser photolysis for O( 1 D) production and pulsed laser-induced fluorescence in the vacuum ultraviolet wavelength range (VUV LIF) for O( 1 D) detection. Theoretical rate constants were obtained using the ring polymer molecular dynamics (RPMD) approach over the two lowest potential energy surfaces 1 1 A' and 1 1 A″, which possess barrierless and thermally activated energy profiles, respectively. Both the experimental and theoretical rate constants exhibit a weak temperature dependence. The theoretical results show the dominant role of the 1 1 A' ground state and that contribution of the 1 1 A″ excited state to the total thermal rate decreases dramatically at lower temperature. Agreement between the experimental and theoretical results is good, and the discrepancy does not exceed 25%. It is argued that these differences are likely to be due to nonadiabatic couplings between the 1 1 A' and 2 1 A' surfaces.

  5. Determination of Methane and Carbon Dioxide Formation Rate Constants for Semi-Continuously Fed Anaerobic Digesters

    Directory of Open Access Journals (Sweden)

    Jan Moestedt

    2015-01-01

    Full Text Available To optimize commercial-scale biogas production, it is important to evaluate the performance of each microbial step in the anaerobic process. Hydrolysis and methanogenesis are usually the rate-limiting steps during digestion of organic waste and by-products. By measuring biogas production and methane concentrations on-line in a semi-continuously fed reactor, gas kinetics can be evaluated. In this study, the rate constants of the fermentative hydrolysis step (kc and the methanogenesis step (km were determined and evaluated in a continuously stirred tank laboratory-scale reactor treating food and slaughterhouse waste and glycerin. A process additive containing Fe2+, Co2+ and Ni2+ was supplied until day 89, after which Ni2+ was omitted. The omission resulted in a rapid decline in the methanogenesis rate constant (km to 70% of the level observed when Ni2+ was present, while kc remained unaffected. This suggests that Ni2+ mainly affects the methanogenic rather than the hydrolytic microorganisms in the system. However, no effect was initially observed when using conventional process monitoring parameters such as biogas yield and volatile fatty acid concentration. Hence, formation rate constants can reveal additional information on process performance and km can be used as a complement to conventional process monitoring tools for semi-continuously fed anaerobic digesters.

  6. Rate constants for the reaction of CF3O radicals with hydrocarbons at 298 K

    DEFF Research Database (Denmark)

    Kelly, C.; Treacy, J.; Sidebottom, H.W.

    1993-01-01

    Rate constant ratios of the reactions of CF3O radicals with a number of hydrocarbons have been determined at 298 +/- 2 K and atmospheric pressure using a relative rate method. Using a previously determined value k(CF30 + C2H6) = 1.2 x 10(-12) cm3 molecule-1 s-1 these rate constant ratios provide...... estimates of the rate constants: k(CF3O + CH4) = (1.2 +/- 0.1) x 10(-14), k(CF3O + c-C3H6) = (3.6 +/- 0.2) x 10(-13), k(CF3O + C3H8) = (4.7 +/- 0.7) x 10(-12), k(CF3O + (CH3)3CH) = (7.2 +/- 0.5) x 10(-12), k(CF3O + C2H4) = (3.0 +/- 0.1) x 10(-11) and k(CF3O + C6H6) = (3.6 +/- 0.1) x 10(-11) cm3 molecule-1 s......-1. The importance of the reactions of CF3O radicals with hydrocarbons under atmospheric conditions is discussed....

  7. Mechanism and rate constants of the Cdc42 GTPase binding with intrinsically disordered effectors.

    Science.gov (United States)

    Pang, Xiaodong; Zhou, Huan-Xiang

    2016-05-01

    Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder-to-order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock-and-coalesce, whereby one segment of the IDP first docks to its subsite on the target surface and the remaining segments subsequently coalesce around their respective subsites. Here we applied our TransComp method within the framework of the dock-and-coalesce mechanism to dissect the binding kinetics of two Rho-family GTPases, Cdc42 and TC10, with two intrinsically disordered effectors, WASP and Pak1. TransComp calculations identified the basic regions preceding the GTPase binding domains (GBDs) of the effectors as the docking segment. For Cdc42 binding with both WASP and Pak1, the calculated docking rate constants are close to the observed overall binding rate constants, suggesting that basic-region docking is the rate-limiting step and subsequent conformational coalescence of the GBDs on the Cdc42 surface is fast. The possibility that conformational coalescence of the WASP GBD on the TC10 surface is slow warrants further experimental investigation. The account for the differences in binding rate constants among the three GTPase-effector systems and mutational effects therein yields deep physical and mechanistic insight into the binding processes. Our approach may guide the selection of mutations that lead to redesigned binding pathways. © 2016 Wiley Periodicals, Inc.

  8. Factors underlying the perception of effort during constant heart rate running above and below the critical heart rate.

    Science.gov (United States)

    Bergstrom, Haley C; Housh, Terry J; Cochrane, Kristen C; Jenkins, Nathaniel D M; Zuniga, Jorge M; Buckner, Samuel L; Goldsmith, Jacob A; Schmidt, Richard J; Johnson, Glen O; Cramer, Joel T

    2015-10-01

    This study examined: (1) the sustainability of the critical heart rate (CHR) minus 5 b min(-1) (CHR - 5) and CHR plus 5 b min(-1) (CHR + 5); (2) the ratings of perceived exertion (RPE), velocity, [Formula: see text], minute ventilation ([Formula: see text]), breathing frequency (f b ), and electromyographic amplitude (EMG AMP) and EMG mean power frequency (MPF) responses during treadmill running at CHR - 5 and CHR + 5 to determine what factors underlie the perception of effort when heart rate (HR) is held constant; and (3) the relationships among RPE, [Formula: see text], and HR, to determine which variable(s) reflect exhaustion during exercise performed at a constant HR. The CHR was determined in eight runners (mean ± SD; age = 24 ± 3 years) from a series of four exhaustive, constant velocity runs. The RPE, velocity, [Formula: see text], [Formula: see text], f b , EMG AMP, and EMG MPF responses were recorded during runs at the CHR - 5 and CHR + 5. At CHR - 5, RPE, f b, and EMG MPF increased, while velocity, [Formula: see text], [Formula: see text], and EMG AMP decreased. At CHR + 5, RPE and f b increased, velocity, [Formula: see text], [Formula: see text], and EMG AMP decreased, and EMG MPF remained constant. The close association between f b and RPE throughout the run at CHR - 5 and during the last 50 % of the run at CHR + 5 indicated that muscle afferents may have provided feedback from metabolic and mechanical stimuli that contributed to the perceptual responses. In addition, only RPE consistently indicated exhaustion and the current findings supported its use to monitor exercise performed at a constant HR.

  9. Likelihood inference of non-constant diversification rates with incomplete taxon sampling.

    Directory of Open Access Journals (Sweden)

    Sebastian Höhna

    Full Text Available Large-scale phylogenies provide a valuable source to study background diversification rates and investigate if the rates have changed over time. Unfortunately most large-scale, dated phylogenies are sparsely sampled (fewer than 5% of the described species and taxon sampling is not uniform. Instead, taxa are frequently sampled to obtain at least one representative per subgroup (e.g. family and thus to maximize diversity (diversified sampling. So far, such complications have been ignored, potentially biasing the conclusions that have been reached. In this study I derive the likelihood of a birth-death process with non-constant (time-dependent diversification rates and diversified taxon sampling. Using simulations I test if the true parameters and the sampling method can be recovered when the trees are small or medium sized (fewer than 200 taxa. The results show that the diversification rates can be inferred and the estimates are unbiased for large trees but are biased for small trees (fewer than 50 taxa. Furthermore, model selection by means of Akaike's Information Criterion favors the true model if the true rates differ sufficiently from alternative models (e.g. the birth-death model is recovered if the extinction rate is large and compared to a pure-birth model. Finally, I applied six different diversification rate models--ranging from a constant-rate pure birth process to a decreasing speciation rate birth-death process but excluding any rate shift models--on three large-scale empirical phylogenies (ants, mammals and snakes with respectively 149, 164 and 41 sampled species. All three phylogenies were constructed by diversified taxon sampling, as stated by the authors. However only the snake phylogeny supported diversified taxon sampling. Moreover, a parametric bootstrap test revealed that none of the tested models provided a good fit to the observed data. The model assumptions, such as homogeneous rates across species or no rate shifts, appear

  10. Normal Amplitude of Electroretinography and Visual Evoked Potential Responses in AβPP/PS1 Mice.

    Science.gov (United States)

    Leinonen, Henri; Lipponen, Arto; Gurevicius, Kestutis; Tanila, Heikki

    2016-01-01

    Alzheimer's disease has been shown to affect vision in human patients and animal models. This may pose the risk of bias in behavior studies and therefore requires comprehensive investigation. We recorded electroretinography (ERG) under isoflurane anesthesia and visual evoked potentials (VEP) in awake amyloid expressing AβPPswe/PS1dE9 (AβPP/PS1) and wild-type littermate mice at a symptomatic age. The VEPs in response to patterned stimuli were normal in AβPP/PS1 mice. They also showed normal ERG amplitude but slightly shortened ERG latency in dark-adapted conditions. Our results indicate subtle changes in visual processing in aged male AβPP/PS1 mice specifically at a retinal level.

  11. Rate constant for the reaction of O(3P) with diacetylene from 210 to 423 K

    Science.gov (United States)

    Mitchell, M. B.; Nava, D. F.; Stief, L. J.

    1986-01-01

    The absolute rate constant for the reaction of O(3P) with diacetylene (C4H2) has been measured as a function of pressure and temperature by the flash-photolysis/resonance-fluorescence method. At 298 K and below, no pressure dependence of the rate constant was observed, but at 423 K a moderate (factor-of-2) increase was detected in the range 3 to 75 torr Ar.Results at or near the high-pressure limit are represented by an Arrhenius expression over the temperature range 210 to 423 K. The results are compared with previous determinations, all of which employed the discharge-flow/mass-spectrometry technique. The mechanism of the reaction is considered, including both primary and secondary processes. The heats of formation of the reactants, adducts, and products for the O(3P) + C4H2 reaction are discussed and contrasted with those for O(3P) + C2H2.

  12. Identifiability of models for time-resolved fluorescence with underlying distributions of rate constants.

    Science.gov (United States)

    Boens, Noël; Van der Auweraer, Mark

    2014-02-01

    The deterministic identifiability analysis of photophysical models for the kinetics of excited-state processes, assuming errorless time-resolved fluorescence data, can verify whether the model parameters can be determined unambiguously. In this work, we have investigated the identifiability of several uncommon models for time-resolved fluorescence with underlying distributions of rate constants which lead to non-exponential decays. The mathematical functions used here for the description of non-exponential fluorescence decays are the stretched exponential or Kohlrausch function, the Becquerel function, the Förster type energy transfer function, decay functions associated with exponential, Gaussian and uniform distributions of rate constants, a decay function with extreme sub-exponential behavior, the Mittag-Leffler function and Heaviside's function. It is shown that all the models are uniquely identifiable, which means that for each specific model there exists a single parameter set that describes its associated fluorescence δ-response function.

  13. Rate constant and possible pressure dependence of the reaction OH + HO2

    Science.gov (United States)

    Demore, W. B.

    1982-01-01

    The technique of laser-induced fluorescence is used to measure steady-state OH concentrations in the photolysis of water vapor at 184.9 nm and 298 K, with O2 added in trace amounts. He or Ar is present at total pressures in the range 75-730 torr. The results are used in deriving the rate-constant ratio of k1 to k5 to the 1/2 power, where k1 and k5 are the rate constants for the reactions OH + HO2 = H2O + O2 and HO2 + HO2 = O2, respectively. When available values of k5 are used, the results give k1 = (1.2 + or - 0.4) x 10 to the -10 cu cm/s at 1-atm pressure, with evidence of a decline of k1 at lower pressures. No water-vapor effect on k1 is observed.

  14. The rate constant for the CO + H2O2 reaction

    DEFF Research Database (Denmark)

    Glarborg, Peter; Marshall, Paul

    2009-01-01

    The rate constant for the reaction CO + H2O2 -> HOCO + OH (R1) at 713 K is determined based on the batch reactor experiments of Baldwin et al. [ R. R. Baldwin, R. W. Walker, S. J. Webster, Combust. Flame 15 (1970) 167] on decomposition of H2O2 sensitized by CO. The value, k(1) (713 K) = 8.1 x 10......(2) cm(3) mol(-1) s(-1), is consistent with spin-unrestricted density functional theory. Extrapolation to a wider temperature range through ab initio calculations yields the rate constant k(1) = 3.6 x 10(4)T(2.5) exp(-14425[K]/T) cm(3) mol(-1) s(-1). The reaction is probably of minor importance...... in combustion. The present analysis reconciles the batch reactor data of Baldwin et al. with recent high-level theoretical work on the CO + HO2 reaction....

  15. Mechanism and Rate Constants of the Cdc42 GTPase Binding with Intrinsically Disordered Effectors

    OpenAIRE

    Pang, Xiaodong; Zhou, Huan-Xiang

    2016-01-01

    Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder-to-order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock-and-coalesce, whereby one segment of the IDP first docks t...

  16. Biotransformation of trace organic chemicals during groundwater recharge: How useful are first-order rate constants?

    KAUST Repository

    Regnery, J.

    2015-05-29

    This study developed relationships between the attenuation of emerging trace organic chemicals (TOrC) during managed aquifer recharge (MAR) as a function of retention time, system characteristics, and operating conditions using controlled laboratory-scale soil column experiments simulating MAR. The results revealed that MAR performance in terms of TOrC attenuation is primarily determined by key environmental parameters (i.e. redox, primary substrate). Soil columns with suboxic and anoxic conditions performed poorly (i.e. less than 30% attenuation of moderately degradable TOrC) in comparison to oxic conditions (on average between 70-100% attenuation for the same compounds) within a residence time of three days. Given this dependency on redox conditions, it was investigated if key parameter-dependent rate constants are more suitable for contaminant transport modeling to properly capture the dynamic TOrC attenuation under field-scale conditions. Laboratory-derived first-order removal kinetics were determined for 19 TOrC under three different redox conditions and rate constants were applied to MAR field data. Our findings suggest that simplified first-order rate constants will most likely not provide any meaningful results if the target compounds exhibit redox dependent biotransformation behavior or if the intention is to exactly capture the decline in concentration over time and distance at field-scale MAR. However, if the intention is to calculate the percent removal after an extended time period and subsurface travel distance, simplified first-order rate constants seem to be sufficient to provide a first estimate on TOrC attenuation during MAR.

  17. A method for computing association rate constants of atomistically represented proteins under macromolecular crowding

    Science.gov (United States)

    Qin, Sanbo; Cai, Lu; Zhou, Huan-Xiang

    2012-12-01

    In cellular environments, two protein molecules on their way to form a specific complex encounter many bystander macromolecules. The latter molecules, or crowders, affect both the energetics of the interaction between the test molecules and the dynamics of their relative motion. In earlier work (Zhou and Szabo 1991 J. Chem. Phys. 95 5948-52), it has been shown that, in modeling the association kinetics of the test molecules, the presence of crowders can be accounted for by their energetic and dynamic effects. The recent development of the transient-complex theory for protein association in dilute solutions makes it possible to easily incorporate the energetic and dynamic effects of crowders. The transient complex refers to a late on-pathway intermediate, in which the two protein molecules have near-native relative separation and orientation, but have yet to form the many short-range specific interactions of the native complex. The transient-complex theory predicts the association rate constant as ka = ka0exp( - ΔG*el/kBT), where ka0 is the ‘basal’ rate constant for reaching the transient complex by unbiased diffusion, and the Boltzmann factors captures the influence of long-range electrostatic interactions between the protein molecules. Crowders slow down the diffusion, therefore reducing the basal rate constant (to kac0), and induce an effective interaction energy ΔGc. We show that the latter interaction energy for atomistic proteins in the presence of spherical crowders is ‘long’-ranged, allowing the association rate constant under crowding to be computed as kac = kac0exp[ - (ΔG*el + ΔG*c)/kBT]. Applications demonstrate that this computational method allows for realistic modeling of protein association kinetics under crowding.

  18. Biotransformation of trace organic chemicals during groundwater recharge: How useful are first-order rate constants?

    Science.gov (United States)

    Regnery, J; Wing, A D; Alidina, M; Drewes, J E

    2015-08-01

    This study developed relationships between the attenuation of emerging trace organic chemicals (TOrC) during managed aquifer recharge (MAR) as a function of retention time, system characteristics, and operating conditions using controlled laboratory-scale soil column experiments simulating MAR. The results revealed that MAR performance in terms of TOrC attenuation is primarily determined by key environmental parameters (i.e., redox, primary substrate). Soil columns with suboxic and anoxic conditions performed poorly (i.e., less than 30% attenuation of moderately degradable TOrC) in comparison to oxic conditions (on average between 70-100% attenuation for the same compounds) within a residence time of three days. Given this dependency on redox conditions, it was investigated if key parameter-dependent rate constants are more suitable for contaminant transport modeling to properly capture the dynamic TOrC attenuation under field-scale conditions. Laboratory-derived first-order removal kinetics were determined for 19 TOrC under three different redox conditions and rate constants were applied to MAR field data. Our findings suggest that simplified first-order rate constants will most likely not provide any meaningful results if the target compounds exhibit redox dependent biotransformation behavior or if the intention is to exactly capture the decline in concentration over time and distance at field-scale MAR. However, if the intention is to calculate the percent removal after an extended time period and subsurface travel distance, simplified first-order rate constants seem to be sufficient to provide a first estimate on TOrC attenuation during MAR. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Constant Growth Rate Can Be Supported by Decreasing Energy Flux and Increasing Aerobic Glycolysis

    Directory of Open Access Journals (Sweden)

    Nikolai Slavov

    2014-05-01

    Full Text Available Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration and of mitochondrial folate-mediated NADPH production (required for oxidative defense. The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.

  20. Competitive kinetics as a tool to determine rate constants for reduction of ferrylmyoglobin by food components

    DEFF Research Database (Denmark)

    Jongberg, Sisse; Lund, Marianne Nissen; Pattison, David I.

    2016-01-01

    Competitive kinetics were applied as a tool to determine apparent rate constants for the reduction of hypervalent haem pigment ferrylmyoglobin (MbFe(IV)=O) by proteins and phenols in aqueous solution of pH 7.4 and I = 1.0 at 25 °C. Reduction of MbFe(IV)=O by a myofibrillar protein isolate (MPI) f...... extracts, though possible confounding reactions need to be considered. These kinetic data suggest that small molar excesses of some plant extracts relative to the MPI thiol concentration should afford significant protection against MbFe(IV)=O-mediated oxidation.......Competitive kinetics were applied as a tool to determine apparent rate constants for the reduction of hypervalent haem pigment ferrylmyoglobin (MbFe(IV)=O) by proteins and phenols in aqueous solution of pH 7.4 and I = 1.0 at 25 °C. Reduction of MbFe(IV)=O by a myofibrillar protein isolate (MPI......) from pork resulted in kMPI = 2.2 ± 0.1 × 104 M-1 s-1. Blocking of the protein thiol groups on the MPI by N-ethylmaleimide (NEM) markedly reduced this rate constant to kMPI-NEM = 1.3 ± 0.4 × 103 M-1 s-1 consistent with a key role for the Cys residues on MPI as targets for haem protein-mediated oxidation...

  1. Reaction of hydroxyl radicals with S-nitrosothiols: determination of rate constants and end product analysis.

    Science.gov (United States)

    Manoj, Veleeparambil M; Aravindakumar, Charuvila T

    2003-04-07

    The reaction of the hydroxyl radical (.OH) with S-nitroso derivatives of cysteine, acetylcysteine and glutathione was studied at neutral and acidic pH. The second-order rate constants were determined by a competition kinetic method using a deoxyribose-thiobarbituric acid assay. The rate constants were diffusion controlled and were 2.27, 1.94 and 1.46 x 10(10) dm3 mol-1 s-1, for S-nitrosocysteine, S-nitrosoacetylcysteine and S-nitrosoglutathione respectively, at neutral pH. The major products of the degradation induced by .OH were found to be the corresponding disulfide (-S-S-) and nitrite (NO2-) at neutral pH as well as at pH 3. Simultaneous proton formation has also been observed. A plausible mechanism based on the formation of an intermediate thiol radical (RS.), as a result of electron transfer from the S-nitrosothiols (RSNOs) to .OH, is proposed for the formation of disulfide and nitrite at both pHs. The high rate constant values and the degradation of these compounds demonstrate the potential role of .OH in RSNO metabolism under physiological conditions.

  2. Rate constants for the formation of SiO by radiative association

    Science.gov (United States)

    Cairnie, M.; Forrey, R. C.; Babb, J. F.; Stancil, P. C.; McLaughlin, B. M.

    2017-10-01

    Accurate molecular data for the low-lying states of SiO are computed and used to calculate rate constants for radiative association (RA) of Si and O. Einstein A-coefficients are also calculated for transitions between all of the bound and quasi-bound levels for each molecular state. The radiative widths are used together with elastic tunnelling widths to define effective RA rate constants which include both direct and indirect (inverse pre-dissociation) formation processes. The indirect process is evaluated for two kinetic models which represent limiting cases for astrophysical environments. The first case scenario assumes an equilibrium distribution of quasi-bound states and would be applicable whenever collisional and/or radiative excitation mechanisms are able to maintain the population. The second case scenario assumes that no excitation mechanisms are available which corresponds to the limit of zero radiation temperature and zero atomic density. Rate constants for SiO formation in realistic astrophysical environments would presumably lie between these two limiting cases.

  3. Rate Constant and Branching Fraction for the NH2 + NO2 Reaction

    DEFF Research Database (Denmark)

    Klippenstein, Stephen J.; Harding, Lawrence B.; Glarborg, Peter

    2013-01-01

    The NH2 + NO2 reaction has been studied experimentally and theoretically. On the basis of laser photolysis/LIF experiments, the total rate constant was determined over the temperature range 295–625 K as k1,exp(T) = 9.5 × 10–7(T/K)−2.05 exp(−404 K/T) cm3 molecule–1 s–1. This value is in the upper...... range of data reported for this temperature range. The reactions on the NH2 + NO2 potential energy surface were studied using high level ab initio transition state theory (TST) based master equation methods, yielding a rate constant of k1,theory(T) = 7.5 × 10–12(T/K)−0.172 exp(687 K/T) cm3 molecule–1 s...... with the measured overall rate constant but tend to overestimate the branching ratio defined as β = k1a/(k1a + k1b) at lower temperatures. Modest adjustments of the attractive potentials for the reaction yield values of k1a = 4.3 × 10–6(T/K)−2.191 exp(−229 K/T) cm3 molecule–1 s–1 and k1b = 1.5 × 10–12(T/K)0.032 exp...

  4. Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation

    Directory of Open Access Journals (Sweden)

    Jones Phill

    2011-02-01

    Full Text Available Abstract Background Several familial Alzheimer disease (FAD mutations within the transmembrane region of the amyloid precursor protein (APP increase the Aβ42/40 ratio without increasing total Aβ production. In the present study, we analyzed the impact of FAD mutations and γ-secretase modulators (GSMs that alter the Aβ42/40 ratio on APP C-terminus (CT positioning relative to the membrane, reasoning that changes in the alignment of the APP intramembranous domain and presenilin 1 (PS1 may impact the PS1/γ-secretase cleavage site on APP. Results By using a Förster resonance energy transfer (FRET-based technique, fluorescent lifetime imaging microscopy (FLIM, we show that Aβ42/40 ratio-modulating factors which target either APP substrate or PS1/γ-secretase affect proximity of the APP-CT to the membrane and change PS1 conformation. Conclusions Thus, we propose that there is a reciprocal relationship between APP-CT positioning relative to the membrane and PS1 conformation, suggesting that factors that modulate either APP positioning in the membrane or PS1 conformation could be exploited therapeutically.

  5. CART treatment improves memory and synaptic structure in APP/PS1 mice.

    Science.gov (United States)

    Jin, Jia-li; Liou, Anthony K F; Shi, Yejie; Yin, Kai-lin; Chen, Ling; Li, Ling-ling; Zhu, Xiao-lei; Qian, Lai; Yang, Rong; Chen, Jun; Xu, Yun

    2015-05-11

    Major characteristics of Alzheimer's disease (AD) include deposits of β-amyloid (Aβ) peptide in the brain, loss of synapses, and cognitive dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently been reported to attenuate Aβ-induced toxicity. In this study, CART localization in APP/PS1 mice was characterized and the protective effects of exogenous CART treatment were examined. Compared to age-matched wild type mice, 8-month-old APP/PS1 mice had significantly greater CART immunoreactivity in the hippocampus and cortex. A strikingly similar pattern of Aβ plaque-associated CART immunoreactivity was observed in the cortex of AD cases. Treatment of APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was associated with improvements in synaptic ultrastructure and long-term potentiation, but not a reduction of the Aβ plaques. Exogenous CART treatment in APP/PS1 mice prevented depolarization of the mitochondrial membrane and stimulated mitochondrial complex I and II activities, resulting in an increase in ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART treatment reduced multiple neuropathological measures and improved memory in APP/PS1 mice, and may therefore be a promising and novel therapy for AD.

  6. Reaction rate constants of H-abstraction by OH from large ketones: Measurements and site-specific rate rules

    KAUST Repository

    Badra, Jihad

    2014-01-01

    Reaction rate constants of the reaction of four large ketones with hydroxyl (OH) are investigated behind reflected shock waves using OH laser absorption. The studied ketones are isomers of hexanone and include 2-hexanone, 3-hexanone, 3-methyl-2-pentanone, and 4-methl-2-pentanone. Rate constants are measured under pseudo-first-order kinetics at temperatures ranging from 866 K to 1375 K and pressures near 1.5 atm. The reported high-temperature rate constant measurements are the first direct measurements for these ketones under combustion-relevant conditions. The effects of the position of the carbonyl group (CO) and methyl (CH3) branching on the overall rate constant with OH are examined. Using previously published data, rate constant expressions covering, low-to-high temperatures, are developed for acetone, 2-butanone, 3-pentanone, and the hexanone isomers studied here. These Arrhenius expressions are used to devise rate rules for H-abstraction from various sites. Specifically, the current scheme is applied with good success to H-abstraction by OH from a series of n-ketones. Finally, general expressions for primary and secondary site-specific H-abstraction by OH from ketones are proposed as follows (the subscript numbers indicate the number of carbon atoms bonded to the next-nearest-neighbor carbon atom, the subscript CO indicates that the abstraction is from a site next to the carbonyl group (CO), and the prime is used to differentiate different neighboring environments of a methylene group):P1,CO = 7.38 × 10-14 exp(-274 K/T) + 9.17 × 10-12 exp(-2499 K/T) (285-1355 K)S10,CO = 1.20 × 10-11 exp(-2046 K/T) + 2.20 × 10-13 exp(160 K/T) (222-1464 K)S11,CO = 4.50 × 10-11 exp(-3000 K/T) + 8.50 × 10-15 exp(1440 K/T) (248-1302 K)S11′,CO = 3.80 × 10-11 exp(-2500 K/T) + 8.50 × 10-15 exp(1550 K/T) (263-1370 K)S 21,CO = 5.00 × 10-11 exp(-2500 K/T) + 4.00 × 10-13 exp(775 K/T) (297-1376 K) © 2014 the Partner Organisations.

  7. Quantitative structure-reactivity relationships of hydroxyl radical rate constants for linear and cyclic volatile methylsiloxanes.

    Science.gov (United States)

    Kim, Jaeshin; Xu, Shihe

    2017-07-18

    An accurate understanding of the fate of volatile methylsiloxanes (VMS) in air is crucial for determining their persistence and concentrations in the environment. Although oxidation by atmospheric hydroxyl radicals (•OH) is considered as a major degradation mechanism for airborne VMS, the existing bimolecular rate constants with •OH measured and modeled for any given VMS compound varied greatly, depending on the approaches used to generate the data. The objectives of the present study were to measure •OH reaction rate constants for 4 cyclic and 4 linear VMS based on a relative rate method using a newly designed atmospheric chamber and to establish structure-reactivity relationships for the kinetics. In the past, the reaction rate constants for VMS were generally recognized to increase with the number of the methyl groups per molecule, the only differential factor in the existing models. However, the new measurements indicated that molecular structure should also be considered in the prediction of the reaction rates. Better empirical models were developed by simple and multiple linear regressions of the measured values from the present study and the literature. A high correlation existed for the reaction rates with the number of the methyl group attached at 2 distinct siloxane structures (i.e., linear and cyclic VMS). Even better correlations were obtained with one or 2 molecular descriptors that are directly related to the size of VMS, which, in turn, not only depend on the number of methyl groups, but the linear/cyclic structures as well for permethylsiloxanes. Environ Toxicol Chem 2017;9999:1-6. © 2017 SETAC. © 2017 SETAC.

  8. Long-crack growth rate data: Constant amplitude and FALSTAFF loading

    Science.gov (United States)

    Phillips, E. P.

    1988-01-01

    This annex describes test procedures and presents the results from the tests for conventional, long-crack growth rate data. These data were used for comparisons with the short-crack growth rate data. Data were generated in tests with constant stress ratio load sequences (R = -2, -1, 0, and 0.5) and with the FALSTAFF load sequence. Results for long-crack tests with the Gaussian load sequence are discussed. The constant stress ratio tests included decreasing, increasing, and constant load amplitude sequences. All cracks exceeded 6 mm in length when data were taken. All tests were conducted on center-cracked specimens of 2024-T3 aluminum alloy sheet taken from a large stock of this material held at the NASA Langley Research Center for fatigue research programs. The baseline long-crack growth rate data for this AGARD program were generated using 50 mm wide, center-cracked specimens which were cut from some of the same sheets that were used to make the edge-notched, short-crack specimens. At growth rates below about 10 to the -5 mm/cycle, the baseline data were supplemented by data generated using 76 mm wide specimens made from sheets other than those used for the short-crack program. At growth rates above about 10 to the -5 mm/cycle, the baseline data were supplemented by data generated using 305 mm wide specimens made from sheets other than those used for the other two specimen sizes. The results from the 305 mm specimens were published in 1969. All specimen configurations are shown.

  9. Rate constant and thermochemistry for K + O2 + N2 = KO2 + N2

    DEFF Research Database (Denmark)

    Sorvajärvi, Tapio; Viljanen, Jan; Toivonen, Juha

    2015-01-01

    in the form of double exponential decays of [K], which yielded both kR1 and the equilibrium constant for KO2 formation. kR1 can be summarized as 1.07 × 10-30(T/1000 K)-0.733 cm6 molecule-2 s-1. Combination with literature values leads to a recommended kR1 of 5.5 × 10-26T-1.55 exp(-10/T) cm6 molecule-2 s-1...... line width diode laser. Experiments were carried out with O2/N2 mixtures at a total pressure of 1 bar, over 748-1323 K. At the lower temperatures single exponential decays of [K] yielded the third-order rate constant for addition, kR1, whereas at higher temperatures equilibration was observed...

  10. Shock tube measurements of the rate constants for seven large alkanes+OH

    KAUST Repository

    Badra, Jihad

    2015-01-01

    Reaction rate constants for seven large alkanes + hydroxyl (OH) radicals were measured behind reflected shock waves using OH laser absorption. The alkanes, n-hexane, 2-methyl-pentane, 3-methyl-pentane, 2,2-dimethyl-butane, 2,3-dimethyl-butane, 2-methyl-heptane, and 4-methyl-heptane, were selected to investigate the rates of site-specific H-abstraction by OH at secondary and tertiary carbons. Hydroxyl radicals were monitored using narrow-line-width ring-dye laser absorption of the R1(5) transition of the OH spectrum near 306.7 nm. The high sensitivity of the diagnostic enabled the use of low reactant concentrations and pseudo-first-order kinetics. Rate constants were measured at temperatures ranging from 880 K to 1440 K and pressures near 1.5 atm. High-temperature measurements of the rate constants for OH + n-hexane and OH + 2,2-dimethyl-butane are in agreement with earlier studies, and the rate constants of the five other alkanes with OH, we believe, are the first direct measurements at combustion temperatures. Using these measurements and the site-specific H-abstraction measurements of Sivaramakrishnan and Michael (2009) [1,2], general expressions for three secondary and two tertiary abstraction rates were determined as follows (the subscripts indicate the number of carbon atoms bonded to the next-nearest-neighbor carbon): S20=1.58×10-11exp(-1550K/T)cm3molecule-1s-1(887-1327K)S30=2.37×10-11exp(-1850K/T)cm3molecule-1s-1(887-1327K)S21=4.5×10-12exp(-793.7K/T)cm3molecule-1s-1(833-1440K)T100=2.85×10-11exp(-1138.3K/T)cm3molecule-1s-1(878-1375K)T101=7.16×10-12exp(-993K/T)cm3molecule-1s-1(883-1362K) © 2014 The Combustion Institute.

  11. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

  12. Ozonation of norfloxacin and levofloxacin in water: Specific reaction rate constants and defluorination reaction.

    Science.gov (United States)

    Ling, Wencui; Ben, Weiwei; Xu, Ke; Zhang, Yu; Yang, Min; Qiang, Zhimin

    2018-03-01

    The degradation kinetics and mechanism of two typical fluoroquinolones (FQs), norfloxacin (NF) and levofloxacin (LOF), by ozone in water were investigated. Semi-continuous mode and competition kinetics mode experiments were conducted to determine the reaction rate constants of target FQs with ozone and OH, separately. Results indicate that both NF and LOF were highly reactive toward ozone, and the reactivity was strongly impacted by the solution pH. The specific reaction rate constants of the diprotonated, monoprotonated and deprotonated species were determined to be 7.20 × 10 2 , 8.59 × 10 3 , 4.54 × 10 5  M -1  s -1 respectively for NF and 1.30 × 10 3 , 1.40 × 10 4 , 1.33 × 10 6  M -1  s -1 respectively for LOF. The reaction rate constants of target FQs toward OH were measured to be (4.81-7.41) × 10 9  M -1  s -1 in the pH range of 6.3-8.3. Furthermore, NF was selected as a model compound to clarify the degradation pathways, with a particular focus on the defluorination reaction. The significant release of F - ions and the formation of three F-free organic byproducts indicated that defluorination was a prevalent pathway in ozonation of FQs, while six F-containing organic byproducts indicated that ozone also attacked the piperazinyl and quinolone moieties. Escherichia coli growth inhibition tests revealed that ozonation could effectively eliminate the antibacterial activity of target FQ solutions, and the residual antibacterial activity had a negative linear correlation with the released F - concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

    Science.gov (United States)

    Tian, Xin; Li, Hua; Jiang, Xiaoyu; Xie, Jingping; Gore, John C.; Xu, Junzhong

    2017-02-01

    Two diffusion-based approaches, CG (constant gradient) and FEXI (filtered exchange imaging) methods, have been previously proposed for measuring transcytolemmal water exchange rate constant kin, but their accuracy and feasibility have not been comprehensively evaluated and compared. In this work, both computer simulations and cell experiments in vitro were performed to evaluate these two methods. Simulations were done with different cell diameters (5, 10, 20 μm), a broad range of kin values (0.02-30 s-1) and different SNR's, and simulated kin's were directly compared with the ground truth values. Human leukemia K562 cells were cultured and treated with saponin to selectively change cell transmembrane permeability. The agreement between measured kin's of both methods was also evaluated. The results suggest that, without noise, the CG method provides reasonably accurate estimation of kin especially when it is smaller than 10 s-1, which is in the typical physiological range of many biological tissues. However, although the FEXI method overestimates kin even with corrections for the effects of extracellular water fraction, it provides reasonable estimates with practical SNR's and more importantly, the fitted apparent exchange rate AXR showed approximately linear dependence on the ground truth kin. In conclusion, either CG or FEXI method provides a sensitive means to characterize the variations in transcytolemmal water exchange rate constant kin, although the accuracy and specificity is usually compromised. The non-imaging CG method provides more accurate estimation of kin, but limited to large volume-of-interest. Although the accuracy of FEXI is compromised with extracellular volume fraction, it is capable of spatially mapping kin in practice.

  14. Rate Constant of the Reaction between CH3O2Radicals and OH Radicals Revisited.

    Science.gov (United States)

    Assaf, Emmanuel; Song, Bo; Tomas, Alexandre; Schoemaecker, Coralie; Fittschen, Christa

    2016-11-17

    The reaction between CH 3 O 2 and OH radicals has been studied in a laser photolysis cell using the reaction of F atoms with CH 4 and H 2 O for the simultaneous generation of both radicals, with F atoms generated through 248 nm photolysis of XeF 2 . An experimental setup combining cw-Cavity Ring Down Spectroscopy (cw-CRDS) and high repetition rate laser-induced fluorescence (LIF) to a laser photolysis cell has been used. The absolute concentration of CH 3 O 2 was measured by cw-CRDS, while the relative concentration of OH(v = 0) radicals was determined by LIF. To remove dubiety from the quantification of CH 3 O 2 by cw-CRDS in the near-infrared, its absorption cross section has been determined at 7489.16 cm -1 using two different methods. A rate constant of k 1 = (1.60 ± 0.4) × 10 -10 cm 3 s -1 has been determined at 295 K, nearly a factor of 2 lower than an earlier determination from our group ((2.8 ± 1.4) × 10 -10 cm 3 s -1 ) using CH 3 I photolysis as a precursor. Quenching of electronically excited I atoms (from CH 3 I photolysis) in collision with OH(v = 0) is suspected to be responsible for a bias in the earlier, fast rate constant.

  15. Reconsideration of the rate constant for the reaction of hydroxyl radicals with nitric acid

    Energy Technology Data Exchange (ETDEWEB)

    Brown, S.S.; Talukdar, R.K.; Ravishankara, A.R. [National Oceanic and Atmospheric Administration, Boulder, CO (United States). Aeronomy Lab.]|[Univ. of Colorado, Boulder, CO (United States)

    1999-04-22

    The authors report rate coefficients for the reaction of OH with HNO{sub 3}, k{sub 1}, between 10 and 500 Torr of He, SF{sub 6}, N{sub 2}, and O{sub 2} and at 10 different temperatures between 200 and 375 K. They generated OH via pulsed photolysis of HNO{sub 3} and monitored the [OH] temporal profile via pulsed laser induced fluorescence. Below 300 K the value of k{sub 1} increases rapidly with decreasing temperature and depends on pressure. The pressure dependence of k{sub 1} at low temperature is significantly larger than that obtained by extrapolation of the currently available data. The pressure and temperature dependence is most likely due to a competition between direct abstraction and reactive complex formation. A rate constant expression derived from such a mechanism gives a global fit for k{sub 1} that is applicable to atmospheric conditions. The new rate constant alters the calculated NO{sub 2} to HNO{sub 3} ratio in the lower stratosphere.

  16. Reaction rate constants and mean population percentage for nitrifiers in an alternating oxidation ditch system.

    Science.gov (United States)

    Mantziaras, I D; Katsiri, A

    2011-01-01

    This paper presents a methodology for the determination of reaction rate constants for nitrifying bacteria and their mean population percentage in biomass in an alternating oxidation ditch system. The method used is based on the growth rate equations of the ASM1 model (IWA) (Henze et al. in Activated sludge models ASM1, ASM2, ASM2d, and ASM3. IWA Scientific and Technical Report no. 9, IWA Publishing, London, UK, 2000) and the application of mass balance equations for nitrifiers and ammonium nitrogen in an operational cycle of the ditch system. The system consists of two ditches operating in four phases. Data from a large-scale oxidation ditch pilot plant with a total volume of 120 m(3) within an experimental period of 8 months was used. Maximum specific growth rate for autotrophs (μ(A)) and the half-saturation constant for ammonium nitrogen (K(NH)) were found to be 0.36 day(-1) and 0.65 mgNH(4)-N/l, respectively. Additionally, the average population percentage of the nitrifiers in the biomass was estimated to be around 3%.

  17. Tunneling Rate Constants for H2CO+H on Amorphous Solid Water Surfaces

    Science.gov (United States)

    Song, Lei; Kästner, Johannes

    2017-12-01

    Formaldehyde (H2CO) is one of the most abundant molecules observed in the icy mantle covering interstellar grains. Studying its evolution can contribute to our understanding of the formation of complex organic molecules in various interstellar environments. In this work, we investigated the hydrogenation reactions of H2CO yielding CH3O, CH2OH, and the hydrogen abstraction resulting in H2+HCO on an amorphous solid water (ASW) surface using a quantum mechanics/molecular mechanics (QM/MM) model. The binding energies of H2CO on the ASW surface vary broadly, from 1000 to 9370 K. No correlation was found between binding energies and activation energies of hydrogenation reactions. Combining instanton theory with QM/MM modeling, we calculated rate constants for the Langmuir–Hinshelwood and the Eley–Rideal mechanisms for the three product channels of H+H2CO surface reactions down to 59 K. We found that the channel producing CH2OH can be ignored, owing to its high activation barrier leading to significantly lower rates than the other two channels. The ASW surface influences the reactivity in favor of formation of CH3O (branching ratio ∼80%) and hinders the H2CO dissociation into H2+HCO. In addition, kinetic isotope effects are strong in all reaction channels and vary strongly between the channels. Finally, we provide fits of the rate constants to be used in astrochemical models.

  18. Methane combustion kinetic rate constants determination: an ill-posed inverse problem analysis

    Directory of Open Access Journals (Sweden)

    Bárbara D. L. Ferreira

    2013-01-01

    Full Text Available Methane combustion was studied by the Westbrook and Dryer model. This well-established simplified mechanism is very useful in combustion science, for computational effort can be notably reduced. In the inversion procedure to be studied, rate constants are obtained from [CO] concentration data. However, when inherent experimental errors in chemical concentrations are considered, an ill-conditioned inverse problem must be solved for which appropriate mathematical algorithms are needed. A recurrent neural network was chosen due to its numerical stability and robustness. The proposed methodology was compared against Simplex and Levenberg-Marquardt, the most used methods for optimization problems.

  19. Power consumption analysis of constant bit rate video transmission over 3G networks

    DEFF Research Database (Denmark)

    Ukhanova, Ann; Belyaev, Evgeny; Wang, Le

    2012-01-01

    This paper presents an analysis of the power consumption of video data transmission with constant bit rate over 3G mobile wireless networks. The work includes the description of the radio resource control transition state machine in 3G networks, followed by a detailed power consumption analysis...... for the 3GPP transition state machine that allows to decrease power consumption on a mobile device taking signaling traffic, buffer size and latency restrictions into account. Furthermore, we discuss the gain in power consumption vs. PSNR for transmitted video and show the possibility of performing power...... consumption management based on the requirements for the video quality....

  20. Power consumption analysis of constant bit rate data transmission over 3G mobile wireless networks

    DEFF Research Database (Denmark)

    Wang, Le; Ukhanova, Ann; Belyaev, Evgeny

    2011-01-01

    This paper presents the analysis of the power consumption of data transmission with constant bit rate over 3G mobile wireless networks. Our work includes the description of the transition state machine in 3G networks, followed by the detailed energy consumption analysis and measurement results...... of the radio link power consumption. Based on these description and analysis, we propose power consumption model. The power model was evaluated on the smartphone Nokia N900, which follows a 3GPP Release 5 and 6 supporting HSDPA/HSPA data bearers. Further we propose method of parameters selection for 3GPP...... transition state machine that allows to decrease power consumption on the mobile device....

  1. Rapid estimation of glucosinolate thermal degradation rate constants in leaves of Chinese kale and broccoli (Brassica oleracea) in two seasons.

    Science.gov (United States)

    Hennig, Kristin; Verkerk, Ruud; Bonnema, Guusje; Dekker, Matthijs

    2012-08-15

    Kinetic modeling was used as a tool to quantitatively estimate glucosinolate thermal degradation rate constants. Literature shows that thermal degradation rates differ in different vegetables. Well-characterized plant material, leaves of broccoli and Chinese kale plants grown in two seasons, was used in the study. It was shown that a first-order reaction is appropriate to model glucosinolate degradation independent from the season. No difference in degradation rate constants of structurally identical glucosinolates was found between broccoli and Chinese kale leaves when grown in the same season. However, glucosinolate degradation rate constants were highly affected by the season (20-80% increase in spring compared to autumn). These results suggest that differences in glucosinolate degradation rate constants can be due to variation in environmental as well as genetic factors. Furthermore, a methodology to estimate rate constants rapidly is provided to enable the analysis of high sample numbers for future studies.

  2. Periods of constant and falling-rate for infrared drying of carrot slices Períodos de secagem constante e decrescente de fatias de cenoura por infravermelho

    Directory of Open Access Journals (Sweden)

    Fernando M. Botelho

    2011-08-01

    Full Text Available The aim of this work was to study the infrared drying process of carrot slices and to determine coefficients related to the heat and mass transfer of the process. Fresh carrots were used, dried until constant weight in a dryer with infrared heating source. Different models were utilized to fit the experimental data of constant and falling drying rate periods. It was verified that the coefficients of heat and mass transfer, during the constant drying rate, significantly increased with temperature on rise. The Diffusion Approximation, Two Terms, Midili and Verna models satisfactory represented the falling period of drying rate of carrot slices. The effective diffusion coefficient increased with temperature and this relationship can be represented by the Arrhenius equation, obtaining activation energy to the drying process of 29.092 kJ mol-1.Com este trabalho objetivou-se estudar o processo de secagem por infravermelho das fatias de cenoura e determinar alguns coeficientes referentes à transferência de calor e massa do processo. Utilizaram-se cenouras frescas, secadas até massa constante em um secador com fonte de aquecimento por infravermelho. Aos dados experimentais se ajustaram diferentes modelos para os períodos de taxa de secagem constante e decrescentes. Verificou-se que os coeficientes transferência de calor e massa, referentes ao período de secagem constante, aumentaram significativamente com o aumento da temperatura e que os modelos Aproximação da Difusão, Dois Termos, Midili e Verna representaram satisfatoriamente o período de secagem decrescente das fatias de cenoura. O coeficiente de difusão efetivo aumentou com a temperatura e esta relação pode ser representada pela Equação de Arrhenius, obtendo-se uma energia de ativação para o processo de secagem de 29,092 kJ mol-1.

  3. Effects of Water Molecule on CO Oxidation by OH: Reaction Pathways, Kinetic Barriers, and Rate Constants.

    Science.gov (United States)

    Zhang, Linyao; Yang, Li; Zhao, Yijun; Zhang, Jiaxu; Feng, Dongdong; Sun, Shaozeng

    2017-07-06

    The water dilute oxy-fuel combustion is a clean combustion technology for near-zero emission power; and the presence of water molecule could have both kinetic and dynamic effects on combustion reactions. The reaction OH + CO → CO 2 + H, one of the most important elementary reactions, has been investigated by extensive electronic structure calculations. And the effects of a single water molecule on CO oxidation have been studied by considering the preformed OH(H 2 O) complex reacts with CO. The results show little change in the reaction pathways, but the additional water molecule actually increases the vibrationally adiabatic energy barriers (V a G ). Further thermal rate constant calculations in the temperature range of 200 to 2000 K demonstrate that the total low-pressure limit rate constant for the water assisted OH(H 2 O) + CO → CO 2 + H 2 O + H reaction is 1-2 orders lower than that of the water unassisted one, which is consistent with the change of V a G . Therefore, the hydrated radical OH(H 2 O) would actually slow down the oxidation of CO. Meanwhile, comparisons show that the M06-2X/aug-cc-pVDZ method gives a much better estimation in energy and thus is recommended to be employed for direct dynamics simulations.

  4. Reaction of H2with O2in Excited Electronic States: Reaction Pathways and Rate Constants.

    Science.gov (United States)

    Pelevkin, Alexey V; Loukhovitski, Boris I; Sharipov, Alexander S

    2017-12-21

    Comprehensive quantum chemical analysis with the use of the multireference state-averaged complete active space self-consistent field approach was carried out to study the reactions of H 2 with O 2 in a 1 Δ g , b 1 Σ g + , c 1 Σ u - , and A' 3 Δ u electronically excited states. The energetically favorable reaction pathways and possible intersystem crossings have been revealed. The energy barriers were refined employing the extended multiconfiguration quasi-degenerate second-order perturbation theory. It has been shown that the interaction of O 2 (a 1 Δ g ) and O 2 (A' 3 Δ u ) with H 2 occurs through the H-abstraction process with relatively low activation barriers that resulted in the formation of the HO 2 molecule in A″ and A' electronic states, respectively. Meanwhile, molecular oxygen in singlet sigma states (b 1 Σ g + and c 1 Σ u - ) was proved to be nonreactive with respect to the molecular hydrogen. Appropriate rate constants for revealed reaction and quenching channels have been estimated using variational transition-state theory including corrections for the tunneling effect, possible nonadiabatic transitions, and anharmonicity of vibrations for transition states and reactants. It was demonstrated that the calculated reaction rate constant for the H 2 + O 2 (a 1 Δ g ) process is in reasonable agreement with known experimental data. The Arrhenius approximations for these processes have been proposed for the temperature range T = 300-3000 K.

  5. Voltage affects the dissociation rate constant of the m2 muscarinic receptor.

    Directory of Open Access Journals (Sweden)

    Yair Ben Chaim

    Full Text Available G-protein coupled receptors (GPCRs comprise the largest protein family and mediate the vast majority of signal transduction processes in the body. Until recently GPCRs were not considered to be voltage dependent. Newly it was shown for several GPCRs that the first step in GPCR activation, the binding of agonist to the receptor, is voltage sensitive: Voltage shifts the receptor between two states that differ in their binding affinity. Here we show that this shift involves the rate constant of dissociation. We used the m2 muscarinic receptor (m2R a prototypical GPCR and measured directly the dissociation of [(3H]ACh from m2R expressed Xenopus oocytes. We show, for the first time, that the voltage dependent change in affinity is implemented by voltage shifting the receptor between two states that differ in their rate constant of dissociation. Furthermore, we provide evidence that suggest that the above shift is achieved by voltage regulating the coupling of the GPCR to its G protein.

  6. A generalized Forchheimer radial flow model for constant-rate tests

    Science.gov (United States)

    Liu, Ming-Ming; Chen, Yi-Feng; Zhan, Hongbin; Hu, Ran; Zhou, Chuang-Bing

    2017-09-01

    Models used for data interpretation of constant-rate tests (CRTs) are commonly derived with the assumption of Darcian flow in an idealized integer flow dimension, where the non-Darcian nature of fluid flow and the complexity of flow geometry are disregarded. In this study, a Forchheimer's law-based analytical model is proposed with the assumption of buildup (or drawdown) decomposition for characterizing the non-Darcian flow in a generalized radial formation where the flow dimension n may become non-integer. The proposed model immediately reduces to Barker's (1988) model for Darcian flow in the generalized radial formation and to Mathias et al.'s (2008) model for non-Darcian flow in a two-dimensional confined aquifer. A comparison with numerical simulations shows that the proposed model behaves well at late times for flow dimension n > 1.5. The proposed model is finally applied for data interpretation of the constant-rate pumping tests performed at Ploemeur (Le Borgne et al., 2004), showing that the intrinsic hydraulic conductivity of formations will be underestimated and the specific storage will be overestimated if the non-Darcian effect is ignored. The proposed model is an extension of the generalized radial flow (GRF) model based on Forchheimer's law, which would be of significance for data interpretation of CRTs in aquifers of complex flow geometry in which non-Darcian flow occurs.

  7. Rate constant for the OH + CO reaction - Pressure dependence and the effect of oxygen

    Science.gov (United States)

    Demore, W. B.

    1984-01-01

    The effect of pressure on the rate constant of the OH + CO reaction has been measured for Ar, N2, and SF6 over the pressure range 200-730 torr. All experiments were at room temperature. The method involved laser-induced fluorescence to measure steady-state OH concentrations in the 184.9 nm photolysis of H2O-CO mixtures in the three carrier gases, combined with supplementary measurements of the CO depletion in these same carrier gases in the presence and absence of competing reference reactants. The effect of O2 on the pressure effect was determined. A pressure enhancement of the rate constant was observed for N2 and SF6, but not for Ar, within an experimental error of about 10 percent. The pressure effect for N2 was somewhat lower than previous literature reports, being about 40 percent at 730 torr. For SF6 a factor of two enhancement was seen at 730 torr. In each case it was found that O2 had no effect on the pressure enhancement. The roles of the radical species HCO and HOCO were evaluated.

  8. Determination of the epimerization rate constant of amygdalin by microemulsion electrokinetic chromatography.

    Science.gov (United States)

    Yu, Lishuang; Ye, Hongzhi; Zheng, Lili; Chen, Lidian; Chu, Kedan; Liu, Xianxiang; Xu, Xueqin; Chen, Guonan

    2011-01-01

    A new method for separation and determination of amygdalin and its epimer (neoamygdalin) in the epimerization of amygdalin by MEEKC is proposed. For the chiral separation of amygdalin and neoamygdalin, a running buffer composed of 80 mM sodium cholate, 5.0% v/v butan-1-ol, 0.5% v/v heptane and 94.5% v/v 30 mM Na(2) B(4) O(7) buffer (pH 9.00) is proposed. Under optimum conditions, the basic separation of amygdalin and neoamygdalin can be achieved within 7 min. The calibration curve for amygdalin showed excellent linearity in the concentration range of 20-1000 μg/mL with a detection limit of 5.0 μg/mL (S/N=3). The epimerization rate constant of amygdalin in basic microemulsion was first determined by monitoring the concentration changes of amygdalin, and the epimerization rate constant of amygdalin was found to be 2×10(-3) min(-1) at 25°C under the above optimum microemulsion conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Absolute rate constants for the reaction of hypochlorous acid with protein side chains and peptide bonds

    DEFF Research Database (Denmark)

    Pattison, D I; Davies, Michael Jonathan

    2001-01-01

    , absolute second-order rate constants for the reactions of HOCl with protein side chains, model compounds, and backbone amide (peptide) bonds have been determined at physiological pH values. The reactivity of HOCl with potential reactive sites in proteins is summarized by the series: Met (3.8 x 10(7) M(-1......) x s(-1)) > backbone amides (10-10(-3) M(-1) x s(-1)) > Gln(0.03 M(-1) x s(-1)) approximately Asn (0.03 M(-1) x s(-1)). The rate constants for reaction of HOCl with backbone amides (peptide bonds) vary by 4 orders of magnitude with uncharged peptide bonds reacting more readily with HOCl than those....... Proteins are major targets for this oxidant, and such reaction results in side-chain modification, backbone fragmentation, and cross-linking. Despite a wealth of qualitative data for such reactions, little absolute kinetic data is available to rationalize the in vitro and in vivo data. In this study...

  10. Rate constant for the reaction of atomic oxygen with phosphine at 298 K

    Science.gov (United States)

    Stief, L. J.; Payne, W. A.; Nava, D. F.

    1987-01-01

    The rate constant for the reaction of atomic oxygen with phosphine has been measured at 298 K using flash photolysis combined with time-resolved detection of O(3P) via resonance fluorescence. Atomic oxygen was produced by flash photolysis of N2O or NO highly diluted in argon. The results were shown to be independent of (PH3), (O), total pressure and the source of O(3P). The mean value of all the experiments is k1 = (3.6 + or -0.8) x 10 to the -11th cu cm/s (1 sigma). Two previous measurements of k1 differed by more than an order of magnitude, and the results support the higher value obtained in a discharge flow-mass spectrometry study. A comparison with rate data for other atomic and free radical reactions with phosphine is presented, and the role of these reactions in the aeronomy or photochemistry of Jupiter and Saturn is briefly considered.

  11. Allowance for antibody bivalence in the determination of association rate constants by kinetic exclusion assay.

    Science.gov (United States)

    Winzor, Donald J

    2013-10-15

    This investigation completes the amendment of theoretical expressions for the characterization of antigen-antibody interactions by kinetic exclusion assay-an endeavor that has been marred by inadequate allowance for the consequences of antibody bivalence in its uptake by the affinity matrix (immobilized antigen) that is used to ascertain the fraction of free antibody sites in a solution with defined total concentrations of antigen and antibody. A simple illustration of reacted site probability considerations in action confirms that the square root of the fluorescence response ratio, R(Ag)/R₀, needs to be taken in order to determine the fraction of unoccupied antibody sites, which is the parameter employed to describe the kinetics of antigen uptake in the mixture of antigen and antibody with defined initial composition. The approximately 2-fold underestimation of the association rate constant (k(a)) that emanates from the usual practice of omitting the square root factor gives rise to a corresponding overestimate of the equilibrium dissociation constant (K(d))--a situation that is also encountered in the thermodynamic characterization of antigen-antibody interactions by kinetic exclusion assay. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Rate constants for the slow Mu + propane abstraction reaction at 300 K by diamagnetic RF resonance.

    Science.gov (United States)

    Fleming, Donald G; Cottrell, Stephen P; McKenzie, Iain; Ghandi, Khashayar

    2015-08-14

    The study of kinetic isotope effects for H-atom abstraction rates by incident H-atoms from the homologous series of lower mass alkanes (CH4, C2H6 and, here, C3H8) provides important tests of reaction rate theory on polyatomic systems. With a mass of only 0.114 amu, the most sensitive test is provided by the rates of the Mu atom. Abstraction of H by Mu can be highly endoergic, due to the large zero-point energy shift in the MuH bond formed, which also gives rise to high activation energies from similar zero-point energy corrections at the transition state. Rates are then far too slow near 300 K to be measured by conventional TF-μSR techniques that follow the disappearance of the spin-polarised Mu atom with time. Reported here is the first measurement of a slow Mu reaction rate in the gas phase by the technique of diamagnetic radio frequency (RF) resonance, where the amplitude of the MuH product formed in the Mu + C3H8 reaction is followed with time. The measured rate constant, kMu = (6.8 ± 0.5) × 10(-16) cm(3) s(-1) at 300 K, is surprisingly only about a factor of three slower than that expected for H + C3H8, indicating a dominant contribution from quantum tunneling in the Mu reaction, consistent with elementary transition state theory calculations of the kMu/kH kinetic isotope effect.

  13. Consideration of demand rate in overall equipment effetiveness (OEE on equipment with constant process time

    Directory of Open Access Journals (Sweden)

    Tay C.C.

    2013-06-01

    research should be conducted to test the possibility and to verify the definition of such performance ratio including Takt time on those processes of which its operating time is possibly to be reduced, especially those are not constant and fixed. This piece of research is temporarily done on the process where its operating time is constant from time to time and there is no ideal cycle time possible.Practical implications: The awareness of the overproduction should be emphasized and raised in the intention of pursuing higher OEE value. As the definition proposed such, the process with constant cycle time could even be defined in different performance ratio from time to time regarding to the customer demands and corresponding production rate. These two variables can be adjusted and balanced to increase the OEE value through optimization of average cycle time. Over this, optimization of average cycle time on equipment with constant operating time can be achieved through the optimization of loading number per each processing.Originality/value: The novelty of the paper is the inclusion of customer demand in obtaining OEE value of any particular equipment. Besides that, the equipment without ideal cycle time, which means those processes carried out in constant cycle time are possibly to be evaluated with performance ratio. As consequence of that, the machine utilization and capability used could be quantified and visualized using the performance ratio data of the OEE proposed.

  14. The Reaction Mechanism and Rate Constants in the Radiolysis of Fe2+-Cu2+ Solutions

    DEFF Research Database (Denmark)

    Bjergbakke, Erling; Sehested, Knud; Rasmussen, O. Lang

    1976-01-01

    Pulse radiolysis and gamma radiolysis have been used to study the reaction mechanism in the radiolysis of aqueous solutions of Fe2+ and Cu2+. A reaction scheme has been developed and confirmed by computation of the corresponding complete set of differential equations. The rate constants for some...... of the reactions have been determined at different pH's. $k_{{\\rm Cu}^{+}+{\\rm O}_{2}}=4.6\\times 10^{5}$ and $1.0\\times 10^{6}\\ {\\rm mol}^{-1}\\ {\\rm sec}^{-1}$, $k_{{\\rm Cu}^{+}+{\\rm Fe}^{3+}}=5.5\\times 10^{6}$ and $1.3\\times 10^{7}\\ {\\rm mol}^{-1}\\ {\\rm sec}^{-1}$, $k_{{\\rm Cu}({\\rm III)}+{\\rm Fe}^{2+}}=3.3\\times...

  15. Low-energy electron impact cross-sections and rate constants of NH_2

    Science.gov (United States)

    Bharadvaja, Anand; Kaur, Savinder; Baluja, K. L.

    2017-08-01

    This systematic study reports various electron impact cross-sections, rate constants and transport properties of NH_2 radical in the low-energy limit. The collision study is based on R-matrix formalism and involves the use of various scattering models employing different active spaces. Both electron excited inelastic cross-sections and resonances are found influenced by correlation and polarization effects. The non-relativistic molecular bremsstrahlung radiation cross-section for soft photons, binary encounter Bethe model-based ionization cross-sections and a few molecular properties of the target radical are also reported. The present calculations are found to be in agreement with the available results. This theoretical study provides a pathway to understand collision dynamics and generates data required in various fields of applied physics.

  16. Ozonation of pharmaceutical compounds: Rate constants and elimination in various water matrices.

    Science.gov (United States)

    Javier Benitez, F; Acero, Juan L; Real, Francisco J; Roldán, Gloria

    2009-09-01

    The ozonation of four pharmaceuticals (metoprolol, naproxen, amoxicillin, and phenacetin) in ultra-pure (UP) water was studied in the pH range between 2.5 and 9. The experiments allowed the determination of the apparent rate constants for the reactions between ozone and the selected compounds. The values obtained varied depending on the pH, and ranged between 239 and 1.27x10(4)M(-1) s(-1) for metoprolol; 2.62x10(4) and 2.97x10(5)M(-1)s(-1) for naproxen; 2.31x10(3) and 1.21x10(7)M(-1)s(-1) for amoxicillin; and 215 and 1.57x10(3)M(-1)s(-1) for phenacetin. Due to the acidic nature of these substances, the degree of dissociation of each pharmaceutical was determined at every pH of work, and the specific rate constants of the neutral and ionic species formed were evaluated. Additionally, the simultaneous ozonation of the pharmaceuticals in different water matrices was carried out by considering a groundwater, a surface water from a public reservoir, and three secondary effluents from municipal wastewater treatment plants. The influence of the operating conditions (initial ozone dose, nature of pharmaceuticals and type of water) on the pharmaceuticals elimination efficiency was established, and a kinetic model was proposed for the evaluation of the partial contribution to the global oxidation of both, the direct ozonation reaction and the radical pathway.

  17. Genomic differentiation among two strains of the PS1 clade isolated from geographically separated marine habitats

    KAUST Repository

    Jimenez Infante, Francy M.

    2014-05-22

    Using dilution-to-extinction cultivation, we isolated a strain affiliated with the PS1 clade from surface waters of the Red Sea. Strain RS24 represents the second isolate of this group of marine Alphaproteobacteria after IMCC14465 that was isolated from the East (Japan) Sea. The PS1 clade is a sister group to the OCS116 clade, together forming a putatively novel order closely related to Rhizobiales. While most genomic features and most of the genetic content are conserved between RS24 and IMCC14465, their average nucleotide identity (ANI) is < 81%, suggesting two distinct species of the PS1 clade. Next to encoding two different variants of proteorhodopsin genes, they also harbor several unique genomic islands that contain genes related to degradation of aromatic compounds in IMCC14465 and in polymer degradation in RS24, possibly reflecting the physicochemical differences in the environment they were isolated from. No clear differences in abundance of the genomic content of either strain could be found in fragment recruitment analyses using different metagenomic datasets, in which both genomes were detectable albeit as minor part of the communities. The comparative genomic analysis of both isolates of the PS1 clade and the fragment recruitment analysis provide first insights into the ecology of this group. © 2014 Federation of European Microbiological Societies.

  18. Enhanced penetration of exogenous EPCs into brains of APP/PS1 transgenic mice

    Science.gov (United States)

    Yuan, Xiaoyang; Mei, Bin; Zhang, Le; Zhang, Cuntai; Zheng, Miao; Liang, Huifang; Wang, Wei; Zheng, Jie; Ding, Ling; Zheng, Kai

    2016-01-01

    The aim of this study was to investigate the repair function of exogenous Endothelial progenitor cells (EPCs) for brain microvascular damage of the APP/PS1 transgenic mouse model of Alzheimer’s disease (AD). This study used a density-gradient centrifugation method to isolate mononuclear cells (MNCs) from mouse bone marrow, which were subsequently seeded and cultured. Cells were characterized by morphology and detection of the surface markers CD34 and CD133 at different time points by immunofluorescence (IF) and flow cytometry (FCM). Then, EPCs were transfected with GFP adenoviral vectors (GFP-EPCs). Wild-type (WT) and APP/PS1 transgenic mice both received GFP-EPCs injection through the tail vein, and using a PBS buffer injection as the control. Seven days later, the animals’ brain tissue was isolated. Expression of GFP was detected by quantitative polymerase chain reaction (qPCR) and western-blot (WB), while the fluorescence of GFP within the brains of mice was observed under a fluorescence microscope. Higher mRNA and protein expression of GFP, accompanied with increased green fluorescence, were detected in the brain of GFP-EPCs-injected APP/PS1 mice, as compared with GFP-EPCs-injected WT mice. The results show that the APP/PS1 transgenic mouse model of AD exhibited enhanced penetration of exogenous EPCs into brains than the WT mice. PMID:27186272

  19. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ruijie [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China); Wang, Junjie, E-mail: junjiewang47@yahoo.com [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China); Xu, Feng [Department of Biomedical Engineering, Peking University Third Hospital, Beijing (China); Li, Hua [Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing (China); Zhang, Xile [Department of Radiation Oncology, Peking University Third Hospital, Beijing (China)

    2013-10-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

  20. Effects of environmental enrichment and physical activity on neurogenesis in transgenic PS1/APP mice.

    Science.gov (United States)

    Catlow, Briony J; Rowe, Amanda R; Clearwater, Courtney R; Mamcarz, Maggie; Arendash, Gary W; Sanchez-Ramos, Juan

    2009-02-23

    Rodents exposed to environmental enrichment show many differences, including improved cognitive performance, when compared to those living in standard (impoverished) housing. The purpose of the present study was to determine if a selective increase in neurogenesis occurred in cognitively-protected Tg mice raised in an enriched environment compared to those reared in physical activity housing. At weaning, double Tg APP+PS1 mice were placed into one of three environments: complete environmental enrichment (CE), enhanced physical activity (PA), or individual, impoverished housing (IMP). At 9-10 months of age, Tg mice were injected with BrdU (100 mg/kg BID) followed by euthanasia either 24 h or 2 weeks after the last injection. Unbiased estimates of BrdU positive cells in the hippocampal subgranular zone revealed a significant increase in cellular proliferation in Tg mice raised in CE or PA compared to Tg mice reared in IMP housing. However, counts of BrdU birth-dated cells 2 weeks after labeling showed no difference among the three groups, indicating decreased survival of cells in those groups (CE and PA) with higher cellular proliferation rates in the neurogenic niche. Counts of calretinin-expressing cells, a marker of immature neurons, also indicated no difference among the three groups of mice. In view of our prior study showing that enhanced cognitive activity (but not enhanced physical activity) protects Tg mice against cognitive impairment, the present results indicate that increased generation and survival of new neurons in the hippocampal dentate gyrus is not involved with the cognitively-protective effects of complete CE in Alzheimer's transgenic mice.

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

    Science.gov (United States)

    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…

  2. Assessment of volumetric-modulated arc therapy for constant and variable dose rates

    Directory of Open Access Journals (Sweden)

    Mariluz De Ornelas-Couto

    2017-01-01

    Full Text Available Purpose: The aim of this study is to compare the effects of dose rate on volumetric-modulated arc therapy plans to determine optimal dose rates for prostate and head and neck (HN cases. Materials and Methods: Ten prostate and ten HN cases were retrospectively studied. For each case, seven plans were generated: one variable dose rate (VDR and six constant dose rate (CDR (100–600 monitor units [MUs]/min plans. Prescription doses were: 80 Gy to planning target volume (PTV for the prostate cases, and 70, 60, and 54 Gy to PTV1, PTV2, and PTV3, respectively, for HN cases. Plans were normalized to 95% of the PTV and PTV1, respectively, with the prescription dose. Plans were assessed using Dose-Volume-Histogram metrics, homogeneity index, conformity index, MUs, and delivery time. Results: For the prostate cases, significant differences were found for rectum D35 between VDR and all CDR plans, except CDR500. Furthermore, VDR was significantly different than CDR100 and 200 for bladder D50. Delivery time for all CDR plans and MUs for CDR400–600 were significantly higher when compared to VDR. HN cases showed significant differences between VDR and CDR100, 500 and 600 for D2 to the cord and brainstem. Significant differences were found for delivery time and MUs for all CDR plans, except CDR100 for number of MUs. Conclusion: The most significant differences were observed in delivery time and number of MUs. All-in-all, the best CDR for prostate cases was found to be 300 MUs/min and 200 or 300 MUs/min for HN cases. However, VDR plans are still the choice in terms of MU efficiency and plan quality.

  3. Escape from a cavity through a small window: turnover of the rate as a function of friction constant.

    Science.gov (United States)

    Berezhkovskii, Alexander M; Makhnovskii, Yurii A; Zitserman, Vladimir Yu

    2006-11-21

    To escape from a cavity through a small window the particle has to overcome a high entropy barrier to find the exit. As a consequence, its survival probability in the cavity decays as a single exponential and is characterized by the only parameter, the rate constant. We use simulations to study escape of Langevin particles from a cubic cavity through a small round window in the center of one of the cavity walls with the goal of analyzing the friction dependence of the escape rate. We find that the rate constant shows the turnover behavior as a function of the friction constant, zeta: The rate constant grows at very small zeta, reaches a maximum value which is given by the transition-state theory (TST), and then decreases approaching zero as zeta-->infinity. Based on the results found in simulations and some general arguments we suggest a formula for the rate constant that predicts a turnover of the escape rate for ergodic cavities in which collisions of the particle with the cavity walls are defocusing. At intermediate-to-high friction the formula describes transition between two known results for the rate constant: the TST estimation and the high friction limiting behavior that characterizes escape of diffusing particles. In this range of friction the rate constants predicted by the formula are in good agreement with those found in simulations. At very low friction the rate constants found in simulations are noticeably smaller than those predicted by the formula. This happens because the simulations were run in the cubic cavity which is not ergodic.

  4. An Analytical Formula for Potential Water Vapor in an Atmosphere of Constant Lapse Rate

    Directory of Open Access Journals (Sweden)

    Ali Varmaghani

    2012-01-01

    Full Text Available Accurate calculation of precipitable water vapor (PWV in the atmosphere has always been a matter of importance for meteorologists. Potential water vapor (POWV or maximum precipitable water vapor can be an appropriate base for estimation of probable maximum precipitation (PMP in an area, leading to probable maximum flood (PMF and flash flood management systems. PWV and POWV have miscellaneously been estimated by means of either discrete solutions such as tables, diagrams or empirical methods; however, there is no analytical formula for POWV even in a particular atmospherical condition. In this article, fundamental governing equations required for analytical calculation of POWV are first introduced. Then, it will be shown that this POWV calculation relies on a Riemann integral solution over a range of altitude whose integrand is merely a function of altitude. The solution of the integral gives rise to a series function which is bypassed by approximation of saturation vapor pressure in the range of -55 to 55 degrees Celsius, and an analytical formula for POWV in an atmosphere of constant lapse rate is proposed. In order to evaluate the accuracy of the suggested equation, exact calculations of saturated adiabatic lapse rate (SALR at different surface temperatures were performed. The formula was compared with both the diagrams from the US Weather Bureau and SALR. The results demonstrated unquestionable capability of analytical solutions and also equivalent functions.

  5. Stress corrosion cracking of alloy 600 using the constant strain rate test

    Energy Technology Data Exchange (ETDEWEB)

    Bulischeck, T. S.; van Rooyen, D.

    1980-01-01

    The most recent corrosion problems experienced in nuclear steam generators tubed with Inconel alloy 600 is a phenomenon labeled ''denting''. Denting has been found in various degrees of severity in many operating pressurized water reactors. Laboratory investigations have shown that Inconel 600 exhibits intergranular SCC when subjected to high stresses and exposed to deoxygenated water at elevated temperatures. A research project was initiated at Brookhaven National Laboratory in an attempt to improve the qualitative and quantitative understanding of factors influencing SCC in high temperature service-related environments. An effort is also being made to develop an accelerated test method which could be used to predict the service life of tubes which have been deformed or are actively denting. Several heats of commercial Inconel 600 tubing were procured for testing in deaerated pure and primary water at temperatures from 290 to 365/sup 0/C. U-bend type specimens were used to determine crack initiation times which may be expected for tubes where denting has occurred but is arrested and provide baseline data for judging the accelerating effects of the slow strain rate method. Constant extension rate tests were employed to determine the crack velocities experienced in the crack propagation stage and predict failure times of tubes which are actively denting. 8 refs., 17 figs., 5 tabs.

  6. Rate constant and thermochemistry for K + O2 + N2 = KO2 + N2.

    Science.gov (United States)

    Sorvajärvi, Tapio; Viljanen, Jan; Toivonen, Juha; Marshall, Paul; Glarborg, Peter

    2015-04-09

    The addition reaction of potassium atoms with oxygen has been studied using the collinear photofragmentation and atomic absorption spectroscopy (CPFAAS) method. KCl vapor was photolyzed with 266 nm pulses and the absorbance by K atoms at 766.5 nm was measured at various delay times with a narrow line width diode laser. Experiments were carried out with O2/N2 mixtures at a total pressure of 1 bar, over 748-1323 K. At the lower temperatures single exponential decays of [K] yielded the third-order rate constant for addition, kR1, whereas at higher temperatures equilibration was observed in the form of double exponential decays of [K], which yielded both kR1 and the equilibrium constant for KO2 formation. kR1 can be summarized as 1.07 × 10(-30)(T/1000 K)(-0.733) cm(6) molecule(-2) s(-1). Combination with literature values leads to a recommended kR1 of 5.5 × 10(-26)T(-1.55) exp(-10/T) cm(6) molecule(-2) s(-1) over 250-1320 K, with an error limit of a factor of 1.5. A van't Hoff analysis constrained to fit the computed ΔS298 yields a K-O2 bond dissociation enthalpy of 184.2 ± 4.0 kJ mol(-1) at 298 K and ΔfH298(KO2) = -95.2 ± 4.1 kJ mol(-1). The corresponding D0 is 181.5 ± 4.0 kJ mol(-1). This value compares well with a CCSD(T) extrapolation to the complete basis set limit, with all electrons correlated, of 177.9 kJ mol(-1).

  7. KABAM Version 1.0 User's Guide and Technical Documentation - Appendix H - Methods for Estimating Metabolism Rate Constant

    Science.gov (United States)

    Appendix H of KABAM Version 1.0 documentation related to estimating the metabolism rate constant. KABAM is a simulation model used to predict pesticide concentrations in aquatic regions for use in exposure assessments.

  8. Experimental determination of the high-temperature rate constant for the reaction of OH with sec-butanol.

    Science.gov (United States)

    Pang, Genny A; Hanson, Ronald K; Golden, David M; Bowman, Craig T

    2012-10-04

    The overall rate constant for the reaction of OH with sec-butanol [CH(3)CH(OH)CH(2)CH(3)] was determined from measurements of the near-first-order OH decay in shock-heated mixtures of tert-butylhydroperoxide (as a fast source of OH) with sec-butanol in excess. Three kinetic mechanisms from the literature describing sec-butanol combustion were used to examine the sensitivity of the rate constant determination to secondary kinetics. The overall rate constant determined can be described by the Arrhenius expression 6.97 × 10(-11) exp(-1550/T[K]) cm(3) molecule(-1) s(-1), valid over the temperature range of 888-1178 K. Uncertainty bounds of ±30% were found to adequately account for the uncertainty in secondary kinetics. To our knowledge, the current data represent the first efforts toward an experimentally determined rate constant for the overall reaction of OH with sec-butanol at combustion-relevant temperatures. A rate constant predicted using a structure-activity relationship from the literature was compared to the current data and previous rate constant measurements for the title reaction at atmospheric-relevant temperatures. The structure-activity relationship was found to be unable to correctly predict the measured rate constant at all temperatures where experimental data exist. We found that the three-parameter fit of 4.95 × 10(-20)T(2.66) exp(+1123/T[K]) cm(3) molecule(-1) s(-1) better describes the overall rate constant for the reaction of OH with sec-butanol from 263 to 1178 K.

  9. Comments to ”Analysis of constant rate period of spray drying of slurry” by Liang et al

    DEFF Research Database (Denmark)

    Jørgensen, Kåre; Jensen, Anker; Sloth, Jakob

    2006-01-01

    In the study by Liang et al. [2001. Analysis of constant rate period of spray drying of slurry. Chemical Engineering Science 56, 2205-2213] the Darcy flow of liquid through a pore system of primary particles to the surface of a slurry droplet was applied for the constant rate period. Steep primary...... by Liang et al. is unable to predict the formation of hollow particles. (c) 2005 Elsevier Ltd. All rights reserved....

  10. Comments to "Analysis of constant rate period of spray drying of slurry" by Liang et al., 2001

    DEFF Research Database (Denmark)

    Jørgensen, Kåre; Jensen, Anker Degn; Sloth, Jakob

    2006-01-01

    In the study by Liang et al. [2001. Analysis of constant rate period of spray drying of slurry. Chemical Engineering Science 56, 2205-2213] the Darcy flow of liquid through a pore system of primary particles to the surface of a slurry droplet was applied for the constant rate period. Steep primary...... by Liang et al. is unable to predict the formation of hollow particles....

  11. Regularized learning of linear ordered-statistic constant false alarm rate filters (Conference Presentation)

    Science.gov (United States)

    Havens, Timothy C.; Cummings, Ian; Botts, Jonathan; Summers, Jason E.

    2017-05-01

    The linear ordered statistic (LOS) is a parameterized ordered statistic (OS) that is a weighted average of a rank-ordered sample. LOS operators are useful generalizations of aggregation as they can represent any linear aggregation, from minimum to maximum, including conventional aggregations, such as mean and median. In the fuzzy logic field, these aggregations are called ordered weighted averages (OWAs). Here, we present a method for learning LOS operators from training data, viz., data for which you know the output of the desired LOS. We then extend the learning process with regularization, such that a lower complexity or sparse LOS can be learned. Hence, we discuss what 'lower complexity' means in this context and how to represent that in the optimization procedure. Finally, we apply our learning methods to the well-known constant-false-alarm-rate (CFAR) detection problem, specifically for the case of background levels modeled by long-tailed distributions, such as the K-distribution. These backgrounds arise in several pertinent imaging problems, including the modeling of clutter in synthetic aperture radar and sonar (SAR and SAS) and in wireless communications.

  12. Rate constant for the reaction C2H5 + HBr → C2H6 + Br.

    Science.gov (United States)

    Golden, David M; Peng, Jingping; Goumri, A; Yuan, J; Marshall, Paul

    2012-06-21

    RRKM theory has been employed to analyze the kinetics of the title reaction, in particular, the once-controversial negative activation energy. Stationary points along the reaction coordinate were characterized with coupled cluster theory combined with basis set extrapolation to the complete basis set limit. A shallow minimum, bound by 9.7 kJ mol(-1) relative to C(2)H(5) + HBr, was located, with a very small energy barrier to dissociation to Br + C(2)H(6). The transition state is tight compared to the adduct. The influence of vibrational anharmonicity on the kinetics and thermochemistry of the title reaction were explored quantitatively. With adjustment of the adduct binding energy by ∼4 kJ mol(-1), the computed rate constants may be brought into agreement with most experimental data in the literature, including new room-temperature results described here. There are indications that at temperatures above those studied experimentally, the activation energy may switch from negative to positive.

  13. Dose rate constants for the quantity Hp(3) for frequently used radionuclides in nuclear medicine.

    Science.gov (United States)

    Szermerski, Bastian; Bruchmann, Iris; Behrens, Rolf; Geworski, Lilli

    2016-12-01

    According to recent studies, the human eye lens is more sensitive to ionising radiation than previously assumed. Therefore, the dose limit for personnel occupationally exposed to ionising radiation will be lowered from currently 150 mSv to 20 mSv per year. Currently, no data base for a reliable estimation of the dose to the lens of the eye is available for nuclear medicine. Furthermore, the dose is usually not monitored. The aim of this work was to determine dose rate constants for the quantity Hp(3), which is supposed to estimate the dose to the lens of the eye. For this, Hp(3)-dosemeters were fixed to an Alderson Phantom at different positions. The dosemeters were exposed to radiation from nuclides typically used in nuclear medicine in their geometries analog to their application in nuclear medicine, e.g. syringe or vial. The results show that the handling of high-energy beta (i.e. electron or positron) emitters may lead to a relevant dose to the lens of the eye. For low-energy beta emitters and gamma emitters, an exceeding of the lowered dose limit seems to be unlikely. Copyright © 2015. Published by Elsevier GmbH.

  14. Quantum chemical and conventional TST calculations of rate constants for the OH + alkane reaction

    Energy Technology Data Exchange (ETDEWEB)

    Bravo-Perez, Graciela [Prog. Investig. Medio Ambiente y Seguridad, Instituto Mexicano del Petroleo, Av. Eje Central Lazaro Cardenas 152, 07730, AP 14805 Mexico DF (Mexico)]. E-mail: gbperez@imp.mx; Alvarez-Idaboy, J. Raul [Prog. Investig. Medio Ambiente y Seguridad, Instituto Mexicano del Petroleo, Av. Eje Central Lazaro Cardenas 152, 07730, AP 14805 Mexico DF (Mexico)]. E-mail: jidaboy@imp.mx; Jimenez, Annia Galano [Prog. Investig. Medio Ambiente y Seguridad, Instituto Mexicano del Petroleo, Av. Eje Central Lazaro Cardenas 152, 07730, AP 14805 Mexico DF (Mexico); Cruz-Torres, Armando [Prog. Investig. Medio Ambiente y Seguridad, Instituto Mexicano del Petroleo, Av. Eje Central Lazaro Cardenas 152, 07730, AP 14805 Mexico DF (Mexico)

    2005-04-04

    Reactions of OH with methane, ethane, propane, i-butane, and n-butane have been modeled using ab initio (MP2) and hybrid DFT (BHandHLYP) methods, and the 6-311G(d,p) basis set. Furthermore, single-point calculations at the CCSD(T) level were carried out at the optimized geometries. The rate constants have been calculated using the conventional transition-state theory (CTST). Arrhenius equations are proposed in the temperature range of 250-650 K. Hindered Internal Rotation partition functions calculations were explicitly carried out and included in the total partition functions. These corrections showed to be relevant in the determination of the pre-exponential parameters, although not so important as in the NO{sub 3} + alkane reactions [G. Bravo-Perez, J.R. Alvarez-Idaboy, A. Cruz-Torres, M.E. Ruiz, J. Phys. Chem. A 106 (2002) 4645]. The explicit participation of the tunnel effect has been taken into account. The calculated rate coefficients provide a very good agreement with the experimental data. The best agreement for the overall alkane + OH reactions seemed to occur when the BHandHLYP geometries and partition functions are used. For propane and i-butane, in addition to the respective secondary and tertiary H-abstraction channels, the primary one has been considered. These pathways are confirmed to be significant in spite of the large differences in activation energies between primary and secondary or primary and tertiary channels, respectively of propane and i-butane reactions and should not be disregarded.

  15. Constant false alarm rate algorithm for the dim-small target detection based on the distribution characteristics of target coordinates

    Science.gov (United States)

    Fei, Xiao-Liang; Ren, Kan; Qian, Wei-xian; Wang, Peng-cheng

    2015-10-01

    CFAR (Constant False Alarm Rate) is a key technology in Infrared dim-small target detection system. Because the traditional constant false alarm rate detection algorithm gets the probability density distribution which is based on the pixel information of each area in the whole image and calculates the target segmentation threshold of each area by formula of Constant false alarm rate, the problems including the difficulty of probability distribution statistics and large amount of algorithm calculation and long delay time are existing. In order to solve the above problems effectively, a formula of Constant false alarm rate based on target coordinates distribution is presented. Firstly, this paper proposes a new formula of Constant false alarm rate by improving the traditional formula of Constant false alarm rate based on the single grayscale distribution which objective statistical distribution features are introduced. So the control of false alarm according to the target distribution information is implemented more accurately and the problem of high false alarm that is caused of the complex background in local area as the cloud reflection and the ground clutter interference is solved. At the same time, in order to reduce the amount of algorithm calculation and improve the real-time characteristics of algorithm, this paper divides the constant false-alarm statistical area through two-dimensional probability density distribution of target number adaptively which is different from the general identifying methods of constant false-alarm statistical area. Finally, the target segmentation threshold of next frame is calculated by iteration based on the function of target distribution probability density in image sequence which can achieve the purpose of controlling the false alarm until the false alarm is down to the upper limit. The experiment results show that the proposed method can significantly improve the operation time and meet the real-time requirements on

  16. Behavioural Phenotyping of APPswe/PS1δE9 Mice

    DEFF Research Database (Denmark)

    Olesen, Louise Ørum; Bouzinova, Elena V; Severino, Maurizio

    2016-01-01

    Alzheimer's disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset......-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests. Long-term treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine was applied to assess the role of 5......-HT on the behavioural profile; duration of treatment was 9 months, initiated when mice were 9 months of age. Treatment with paroxetine delays the decline in locomotion, in exploration and risk assessment behaviour, found in the APP/PS1 mice. APP/PS1 mice also exhibit low social activity and less...

  17. Rate constant measurements for the overall reaction of OH + 1-butanol → products from 900 to 1200 K.

    Science.gov (United States)

    Pang, Genny A; Hanson, Ronald K; Golden, David M; Bowman, Craig T

    2012-03-15

    The rate constant for the overall reaction OH + 1-butanol → products was determined in the temperature range 900 to 1200 K from measurements of OH concentration time histories in reflected shock wave experiments of tert-butyl hydroperoxide (TBHP) as a fast source of OH radicals with 1-butanol in excess. Narrow-linewidth laser absorption was employed for the quantitative OH concentration measurement. A detailed kinetic mechanism was constructed that includes updated rate constants for 1-butanol and TBHP kinetics that influence the near-first-order OH concentration decay under the present experimental conditions, and this mechanism was used to facilitate the rate constant determination. The current work improves upon previous experimental studies of the title rate constant by utilizing a rigorously generated kinetic model to describe secondary reactions. Additionally, the current work extends the temperature range of experimental data in the literature for the title reaction under combustion-relevant conditions, presenting the first measurements from 900 to 1000 K. Over the entire temperature range studied, the overall rate constant can be expressed in Arrhenius form as 3.24 × 10(-10) exp(-2505/T [K]) cm(3) molecule(-1) s(-1). The influence of secondary reactions on the overall OH decay rate is discussed, and a detailed uncertainty analysis is performed yielding an overall uncertainty in the measured rate constant of ±20% at 1197 K and ±23% at 925 K. The results are compared with previous experimental and theoretical studies on the rate constant for the title reaction and reasonable agreement is found when the earlier experimental data were reinterpreted.

  18. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice.

    Science.gov (United States)

    Aso, Ester; Sánchez-Pla, Alexandre; Vegas-Lozano, Esteban; Maldonado, Rafael; Ferrer, Isidro

    2015-01-01

    Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer's disease (AD). The present study supports this hypothesis demonstrating that delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Moreover, THC + CBD reduced learning impairment in AβPP/PS1 mice. A significant decrease in soluble Aβ42 peptide levels and a change in plaques composition were also observed in THC + CBD-treated AβPP/PS1 mice, suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Aβ peptide. Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role. Here we observed reduced astrogliosis, microgliosis, and inflammatory-related molecules in treated AβPP/PS1 mice, which were more marked after treatment with THC + CBD than with either THC or CBD. Moreover, other cannabinoid-induced effects were uncovered by a genome-wide gene expression study. Thus, we have identified the redox protein thioredoxin 2 and the signaling protein Wnt16 as significant substrates for the THC + CBD-induced effects in our AD model. In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.

  19. Loss of GABAergic inputs in APP/PS1 mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Tutu Oyelami

    2014-04-01

    Full Text Available Alzheimer's disease (AD is characterized by symptoms which include seizures, sleep disruption, loss of memory as well as anxiety in patients. Of particular importance is the possibility of preventing the progressive loss of neuronal projections in the disease. Transgenic mice overexpressing EOFAD mutant PS1 (L166P and mutant APP (APP KM670/671NL Swedish (APP/PS1 develop a very early and robust Amyloid pathology and display synaptic plasticity impairments and cognitive dysfunction. Here we investigated GABAergic neurotransmission, using multi-electrode array (MEA technology and pharmacological manipulation to quantify the effect of GABA Blockers on field excitatory postsynaptic potentials (fEPSP, and immunostaining of GABAergic neurons. Using MEA technology we confirm impaired LTP induction by high frequency stimulation in APPPS1 hippocampal CA1 region that was associated with reduced alteration of the pair pulse ratio after LTP induction. Synaptic dysfunction was also observed under manipulation of external Calcium concentration and input-output curve. Electrophysiological recordings from brain slice of CA1 hippocampus area, in the presence of GABAergic receptors blockers cocktails further demonstrated significant reduction in the GABAergic inputs in APP/PS1 mice. Moreover, immunostaining of GAD65 a specific marker for GABAergic neurons revealed reduction of the GABAergic inputs in CA1 area of the hippocampus. These results might be linked to increased seizure sensitivity, premature death and cognitive dysfunction in this animal model of AD. Further in depth analysis of GABAergic dysfunction in APP/PS1 mice is required and may open new perspectives for AD therapy by restoring GABAergic function.

  20. Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease.

    Science.gov (United States)

    Poisnel, Géraldine; Hérard, Anne-Sophie; El Tannir El Tayara, Nadine; Bourrin, Emmanuel; Volk, Andreas; Kober, Frank; Delatour, Benoit; Delzescaux, Thierry; Debeir, Thomas; Rooney, Thomas; Benavides, Jésus; Hantraye, Philippe; Dhenain, Marc

    2012-09-01

    Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Application of an Artificial Neural Network to the Prediction of OH Radical Reaction Rate Constants for Evaluating Global Warming Potential.

    Science.gov (United States)

    Allison, Thomas C

    2016-03-03

    Rate constants for reactions of chemical compounds with hydroxyl radical are a key quantity used in evaluating the global warming potential of a substance. Experimental determination of these rate constants is essential, but it can also be difficult and time-consuming to produce. High-level quantum chemistry predictions of the rate constant can suffer from the same issues. Therefore, it is valuable to devise estimation schemes that can give reasonable results on a variety of chemical compounds. In this article, the construction and training of an artificial neural network (ANN) for the prediction of rate constants at 298 K for reactions of hydroxyl radical with a diverse set of molecules is described. Input to the ANN consists of counts of the chemical bonds and bends present in the target molecule. The ANN is trained using 792 (•)OH reaction rate constants taken from the NIST Chemical Kinetics Database. The mean unsigned percent error (MUPE) for the training set is 12%, and the MUPE of the testing set is 51%. It is shown that the present methodology yields rate constants of reasonable accuracy for a diverse set of inputs. The results are compared to high-quality literature values and to another estimation scheme. This ANN methodology is expected to be of use in a wide range of applications for which (•)OH reaction rate constants are required. The model uses only information that can be gathered from a 2D representation of the molecule, making the present approach particularly appealing, especially for screening applications.

  2. Three-minute constant rate step test for detecting exertional dyspnea relief after bronchodilation in COPD

    Directory of Open Access Journals (Sweden)

    Borel B

    2016-11-01

    Full Text Available Benoit Borel,1,2 Courtney A Wilkinson-Maitland,3 Alan Hamilton,4 Jean Bourbeau,5 Hélène Perrault,6 Dennis Jensen,3,5,7 François Maltais2 1Laboratoire HAVAE, Université de Limoges, Limoges, France; 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, 3Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, McGill University, Montréal, QC, 4Boehringer Ingelheim (Canada Limited, Burlington, ON, 5Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Center, Montreal, QC, 6Faculty of Health Sciences, University of Ottawa, Ottawa, ON, 7Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Background: The aim of this study was to evaluate the responsiveness of the 3-minute constant rate step test (3-MST to detect the relief of exertional dyspnea (respiratory discomfort after acute bronchodilation in COPD patients. Patients and methods: A total of 40 patients with moderate-to-severe COPD (mean forced expiratory volume in 1 second: 45.7 (±14.7, % predicted performed four 3-MSTs at randomly assigned stepping rates of 14, 16, 20 and 24 steps/min after inhalation of nebulized ipratropium bromide (500 µg/salbutamol (2.5 mg and saline placebo, which were randomized to order. Patients rated their intensity of perceived dyspnea at the end of each 3-MST using Borg 0–10 category ratio scale. Results: A total of 37 (92.5%, 36 (90%, 34 (85% and 27 (67.5% patients completed all 3 minutes of exercise at 14, 16, 20 and 24 steps/min under both treatment conditions, respectively. Compared with placebo, ipratropium bromide/salbutamol significantly decreased dyspnea at the end of the third minute of exercise at 14 steps/min (by 0.6±1.0 Borg 0–10 scale units, P<0.01 and 16 steps/min (by 0.7±1.3 Borg 0–10 scale

  3. On the ambiguity of the reaction rate constants in multivariate curve resolution for reversible first-order reaction systems.

    Science.gov (United States)

    Schröder, Henning; Sawall, Mathias; Kubis, Christoph; Selent, Detlef; Hess, Dieter; Franke, Robert; Börner, Armin; Neymeyr, Klaus

    2016-07-13

    If for a chemical reaction with a known reaction mechanism the concentration profiles are accessible only for certain species, e.g. only for the main product, then often the reaction rate constants cannot uniquely be determined from the concentration data. This is a well-known fact which includes the so-called slow-fast ambiguity. This work combines the question of unique or non-unique reaction rate constants with factor analytic methods of chemometrics. The idea is to reduce the rotational ambiguity of pure component factorizations by considering only those concentration factors which are possible solutions of the kinetic equations for a properly adapted set of reaction rate constants. The resulting set of reaction rate constants corresponds to those solutions of the rate equations which appear as feasible factors in a pure component factorization. The new analysis of the ambiguity of reaction rate constants extends recent research activities on the Area of Feasible Solutions (AFS). The consistency with a given chemical reaction scheme is shown to be a valuable tool in order to reduce the AFS. The new methods are applied to model and experimental data. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Temperature-Dependent Rate Constants and Substituent Effects for the Reactions of Hydroxyl Radicals With Three Partially Fluorinated Ethers

    Science.gov (United States)

    Hsu, K.-J.; DeMore, W. B.

    1995-01-01

    Rate constants and temperature dependencies for the reactions of OH with CF3OCH3 (HFOC-143a), CF2HOCF2H (HFOC-134), and CF3OCF2H (HFOC-125) were studied using a relative rate technique in the temperature range 298-393 K. The following absolute rate constants were derived: HFOC-143a, 1.9E-12 exp(-1555/T); HFOC-134, 1.9E-12 exp(-2006/T); HFOC-125, 4.7E-13 exp(-2095/T). Units are cm(exp 3)molecule(exp -1) s(exp -1). Substituent effects on OH abstraction rate constants are discussed, and it is shown that the CF3O group has an effect on the OH rate constants similar to that of a fluorine atom. The effects are related to changes in the C-H bond energies of the reactants (and thereby the activation energies) rather than changes in the preexponential factors. On the basis of a correlation of rate constants with bond energies, the respective D(C-H) bond strengths in the three ethers are found to be 102, 104, and 106 kcal/mol, with an uncertainty of about 1 kcal/mol.

  5. Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations

    NARCIS (Netherlands)

    Rogaeva, E. A.; Fafel, K. C.; Song, Y. Q.; Medeiros, H.; Sato, C.; Liang, Y.; Richard, E.; Rogaev, E. I.; Frommelt, P.; Sadovnick, A. D.; Meschino, W.; Rockwood, K.; Boss, M. A.; Mayeux, R.; St George-Hyslop, P.

    2001-01-01

    Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early-onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive

  6. Applications of Cell-Ratio Constant False-Alarm Rate Method in Coherent Doppler Wind Lidar

    Directory of Open Access Journals (Sweden)

    Hao Zhu

    2016-12-01

    Full Text Available A cell-ratio constant false-alarm rate (CR-CFAR method for detecting the Doppler frequency shift is proposed to improve the accuracy of velocity measured by coherent Doppler wind lidar (CWL in low signal-to-noise ratio (SNR environments. The method analyzes the spectrum to solve issues of weak signal submergence in noise encountered in the widely used periodogram method. This characteristic is that the signal region slope is larger than the noise region slope in the frequency spectrum. We combined the ratio and CFAR to propose the CR-CFAR method. The peak area is discriminated from the spectrum using this method. By removing background noise, the peak signal is obtained along with the Doppler shift. To verify the CR-CFAR method, a campaign experiment using both CWL and a commercial Doppler lidar was performed in Hami, China (42°32′ N, 94°03′ E during 1–7 June 2016. The results showed that the proposed method significantly improved the reliability of CWL data under low SNR conditions. The height—at which both horizontal wind speed correlativity and horizontal wind direction correlativity exceeded 0.99—increased by 65 m. The relative deviation of the horizontal wind speed at 120 m decreased from 40.37% to 11.04%. We used the CR-CFAR method to analyze continuous data. A greater number of wind field characteristics were obtained during observation compared to those obtained using the common wind field inversion method.

  7. Evaluating the methane generation rate constant (k value) of low-organic waste at Danish landfills.

    Science.gov (United States)

    Mou, Zishen; Scheutz, Charlotte; Kjeldsen, Peter

    2015-01-01

    The methane (CH4) generation rate constant (k value, yr(-1)) is an essential parameter when using first-order decay (FOD) landfill gas (LFG) generation models to estimate CH4 generation from landfills. Four categories of waste (street cleansing, mixed bulky, shredder, and sludge waste) with a low-organic content, as well as temporarily stored combustible waste, were sampled from four Danish landfills. Anaerobic degradation experiments were set up in duplicate for all waste samples and incubated for 405 days, while the cumulative CH4 generation was continuously monitored. Applying FOD equations to the experimental results, half-life time values (t½, yr) and k values of various waste categories were determined. In general, similar waste categories obtained from different Danish landfills showed similar results. Sludge waste had the highest k values, which were in the range 0.156-0.189 yr(-1). The combustible and street cleansing waste showed k values of 0.023-0.027 yr(-1) and 0.073-0.083 yr(-1), respectively. The lowest k values were obtained for mixed bulky and shredder wastes ranging from 0.013 to 0.017 yr(-1). Most low-organic waste samples showed lower k values in comparison to the default numeric values in current FOD models (e.g., IPCC, LandGEM, and Afvalzorg). Compared with the k values reported in the literature, this research determined low-organic waste for the first time via reliable large-scale and long-term experiments. The degradation parameters provided in this study are valuable when using FOD LFG generation models to estimate CH4 generation from modern landfills that receive only low-organic waste. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 100 kV/2A three-phase constant-current repetitive-rate charging equipment

    CERN Document Server

    Tan Yu Gang; Chen Li Dong; Guo Zhi Gang; Zou Xiao Bing; Luo Min; Cao Shao Yun; Chang An Bi

    2002-01-01

    A 100 kV/2A three-phase constant-current repetitive-rate charging equipment was designed and constructed. A three-phase L-C converter is adopted as constant-current power source. Six Insulated Gate Bipolar Transistors (IGBTs) are connected in parallel to control the stop of charge. A Programmable Logical Controller (PLC) is the central element of the control unit. The equipment is used in the repetitive-rate discharge features test of the switch. It works stably under the conditions of 2A charging current, 10 Hz operating voltage, 100 kV repetitive rate and 1 mu F capacitor

  9. In situ and laboratory determined first-order degradation rate constants of specific organic compounds in an aerobic aquifer

    DEFF Research Database (Denmark)

    Nielsen, P.H.; Bjerg, P.L.; Nielsen, P.

    1996-01-01

    , tetrachloroethene, phenol, o-cresol, 2,4- and 2,6-dichlorophenol, 4,6-o-dichlorocresol, and o- and p-nitrophenol in an aerobic aquifer, All aromatic hydrocarbons were degraded in ISM and LBM experiments. The phenolic hydrocarbons were ail degraded in ISM experiments, but some failed to degrade in LBM experiments...... experiments. First-order degradation rate constants for aromatic and phenolic hydrocarbons ranged between 0.01 and 0.9 day(-1). Local variations in first-order degradation rates and variations between rate constants determined by ISM and LBM were generally with in a factor of 5, but no systematic differences...

  10. Kinetics analysis for development of a rate constant estimation model for ultrasonic degradation reaction of methylene blue.

    Science.gov (United States)

    Kobayashi, Daisuke; Honma, Chiemi; Matsumoto, Hideyuki; Takahashi, Tomoki; Kuroda, Chiaki; Otake, Katsuto; Shono, Atsushi

    2014-07-01

    Ultrasound has been used as an advanced oxidation method for wastewater treatment. Sonochemical degradation of organic compounds in aqueous solution occurs by pyrolysis and/or reaction with hydroxyl radicals. Moreover, kinetics of sonochemical degradation has been proposed. However, the effect of ultrasonic frequency on degradation rate has not been investigated. In our previous study, a simple model for estimating the apparent degradation rate of methylene blue was proposed. In this study, sonochemical degradation of methylene blue was performed at various frequencies. Apparent degradation rate constant was evaluated assuming that sonochemical degradation of methylene blue was a first-order reaction. Specifically, we focused on effects of ultrasonic frequency and power on rate constant, and the applicability of our proposed model was demonstrated. Using this approach, maximum sonochemical degradation rate was observed at 490 kHz, which agrees with a previous investigation into the effect of frequency on the sonochemical efficiency value evaluated by KI oxidation dosimetry. Degradation rate increased with ultrasonic power at every frequency. It was also observed that threshold power must be reached for the degradation reaction to progress. The initial methylene blue concentration and the apparent degradation rate constant have a relation of an inverse proportion. Our proposed model for estimating the apparent degradation rate constant using ultrasonic power and sonochemical efficiency value can apply to this study which extended the frequency and initial concentration range. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Linear free energy relationships between aqueous phase hydroxyl radical reaction rate constants and free energy of activation.

    Science.gov (United States)

    Minakata, Daisuke; Crittenden, John

    2011-04-15

    The hydroxyl radical (HO(•)) is a strong oxidant that reacts with electron-rich sites on organic compounds and initiates complex radical chain reactions in aqueous phase advanced oxidation processes (AOPs). Computer based kinetic modeling requires a reaction pathway generator and predictions of associated reaction rate constants. Previously, we reported a reaction pathway generator that can enumerate the most important elementary reactions for aliphatic compounds. For the reaction rate constant predictor, we develop linear free energy relationships (LFERs) between aqueous phase literature-reported HO(•) reaction rate constants and theoretically calculated free energies of activation for H-atom abstraction from a C-H bond and HO(•) addition to alkenes. The theoretical method uses ab initio quantum mechanical calculations, Gaussian 1-3, for gas phase reactions and a solvation method, COSMO-RS theory, to estimate the impact of water. Theoretically calculated free energies of activation are found to be within approximately ±3 kcal/mol of experimental values. Considering errors that arise from quantum mechanical calculations and experiments, this should be within the acceptable errors. The established LFERs are used to predict the HO(•) reaction rate constants within a factor of 5 from the experimental values. This approach may be applied to other reaction mechanisms to establish a library of rate constant predictions for kinetic modeling of AOPs.

  12. QSARs for phenols and phenolates: oxidation potential as a predictor of reaction rate constants with photochemically produced oxidants.

    Science.gov (United States)

    Arnold, William A; Oueis, Yan; O'Connor, Meghan; Rinaman, Johanna E; Taggart, Miranda G; McCarthy, Rachel E; Foster, Kimberley A; Latch, Douglas E

    2017-03-22

    Quantitative structure-activity relationships (QSARs) for prediction of the reaction rate constants of phenols and phenolates with three photochemically produced oxidants, singlet oxygen, carbonate radical, and triplet excited state sensitizers/organic matter, are developed. The predictive variable is the one-electron oxidation potential (E 1 ), which is calculated for each species using density functional theory. The reaction rate constants are obtained from the literature, and for singlet oxygen, are augmented with new experimental data. Calculated E 1 values have a mean unsigned error compared to literature values of 0.04-0.06 V. For singlet oxygen, a single linear QSAR that includes both phenols and phenolates is developed that predicts experimental rate constants, on average, to within a factor of three. Predictions for only 6 out of 87 compounds are off by more than a factor of 10. A more limited data set for carbonate radical reactions with phenols and phenolates also gives a single linear QSAR with prediction of rate constant being accurate to within a factor of three. The data for the reactions of phenols with triplet state sensitizers demonstrate that two sensitizers, 2-acetonaphthone and methylene blue, most closely predict the reactivity trend of triplet excited state organic matter with phenols. Using sensitizers with stronger reduction potentials could lead to overestimation of rate constants and thus underestimation of phenolic pollutant persistence.

  13. Pressure dependence of the absolute rate constant for the reaction OH + C2H2 from 228 to 413 K

    Science.gov (United States)

    Michael, J. V.; Nava, D. F.; Payne, W. A.; Stief, L. J.; Borkowski, R. P.

    1980-01-01

    The pressure dependence of the absolute rate constant for the reaction of the hydroxyl radical with acetylene, important in both atmospheric and combustion chemistry, is determined for temperatures between 228 and 413 K. The flash photolysis-resonance fluorescence technique was employed at five temperatures over wide ranges of pressure and acetylene concentrations, with the OH produced by water photolysis and hydroxyl resonance fluorescent photons measured by multiscaling techniques. Results indicate that, except at the lowest temperature, the bimolecular rate constant for the reaction depends strongly on total pressure, with the pressure effect becoming more pronounced with increasing temperature. At limiting high pressures, the rate constant is found to be equal to 6.83 + or - 1.19 x 10 to the -12th exp (-646 + or - 47/T) cu cm/molecule per sec, where T is the temperature. Results thus demonstrate the importance of environmental conditions in theoretical studies of atmospheric and combustion product compositions

  14. Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Grace; Earl, Matthew A; Yu, Cedric X [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States)], E-mail: cyu002@umaryland.edu

    2009-11-07

    Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc(TM) deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to {<=}{+-} 5 deg. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was

  15. Temperature dependence of the rate constant of hydrogen isotope interactions with a lithium capillary-porous system under reactor irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tazhibayeva, Irina, E-mail: tazhibayeva@ntsc.kz [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Kulsartov, Timur; Gordienko, Yuri [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Mukanova, Aliya [Al’ Farabi Kazakh National University, Almaty (Kazakhstan); Ponkratov, Yuri; Barsukov, Nikolay; Tulubaev, Evgeniy [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Platacis, Erik [University of Latvia (IPUL), Riga (Latvia); Kenzhin, Ergazy [Shakarim Semey State University, Semey (Kazakhstan)

    2013-10-15

    Highlights: • The experiments with Li CPS sample were carried out at reactor IVG-1.M. • The gas absorption technique was used to study hydrogen isotope interaction with lithium CPS. • The temperature dependence of constants of interaction rate was obtained for various power rates of the reactor. • Determination of the activation energies, and pre-exponents of Arrhenius dependence. • The effect of increase of the rate constant under reaction irradiation. -- Abstract: Experiments with a sample of a lithium capillary-porous system (CPS) were performed at the reactor IVG-1.M of the Institute of Atomic Energy NNC RK to study the effects of neutron irradiation on the parameters of hydrogen isotope interactions with a lithium CPS. The absorption technique was used during the experiments, and this technique allowed the temperature dependences of the hydrogen isotope interaction rate constants with the lithium CPS to be obtained under various reactor powers. The obtained dependencies were used to determine the main interaction parameters: the activation energies and the pre-exponents of the Arrhenius dependence of the hydrogen interaction rate constants with lithium and the lithium CPS. An increase of the hydrogen isotope interaction rate with the lithium CPS was observed under reactor irradiation.

  16. Absolute rate constants for the reaction of NO3 radicals with a series of dienes at 295 K

    DEFF Research Database (Denmark)

    Ellermann, T.; Nielsen, O.J.; Skov, H.

    1992-01-01

    The rate constants for the reaction of NO3 radicals with a series of 7 dienes, 1,3-butadiene, isoprene, 2,3-dimethyl-1,3-butadiene, trans-1,3-pentadiene, cis-1,3-pentadiene, trans,trans-2,4-hexadiene, and 1,3-cyclohexadiene, were measured at 295 K and at a total pressure of 1 atm. The rate constant...... were obtained using the absolute technique of pulse radiolysis combined with kinetic UV-VIS spectroscopy. The results are discussed in terms of reactivity trends and previous literature data....

  17. High-level theoretical study of the reaction between hydroxyl and ammonia: Accurate rate constants from 200 to 2500 K

    Science.gov (United States)

    Nguyen, Thanh Lam; Stanton, John F.

    2017-10-01

    Hydrogen abstraction from NH3 by OH to produce H2O and NH2—an important reaction in combustion of NH3 fuel—was studied with a theoretical approach that combines high level quantum chemistry and advanced chemical kinetics methods. Thermal rate constants calculated from first principles agree well (within 5%-20%) with available experimental data over a temperature range that extends from 200 to 2500 K. Quantum mechanical tunneling effects were found to be important; they lead to a decided curvature and non-Arrhenius behavior for the rate constant.

  18. EFRT M-12 Issue Resolution: Caustic Leach Rate Constants from PEP and Laboratory-Scale Tests

    Energy Technology Data Exchange (ETDEWEB)

    Mahoney, Lenna A.; Rassat, Scot D.; Eslinger, Paul W.; Aaberg, Rosanne L.; Aker, Pamela M.; Golovich, Elizabeth C.; Hanson, Brady D.; Hausmann, Tom S.; Huckaby, James L.; Kurath, Dean E.; Minette, Michael J.; Sundaram, S. K.; Yokuda, Satoru T.

    2009-08-14

    concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before adding caustic. The work described in this report addresses the kinetics of caustic leach under WTP conditions, based on tests performed with a Hanford waste simulant. The tests were completed at the lab-scale and in the PEP, which is a 1/4.5-scale mock-up of key PTF process equipment. The purpose of this report is to summarize the results from both scales that are related to caustic leach chemistry to support a scale-up factor for the submodels to be used in the G2 model, which predicts WTP operating performance. The scale-up factor will take the form of an adjustment factor for the rate constant in the boehmite leach kinetic equation in the G2 model.

  19. Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs

    NARCIS (Netherlands)

    Valtolina, C.|info:eu-repo/dai/nl/412503034; Robben, J.H.|info:eu-repo/dai/nl/266740790; Uilenreef, J.J.|info:eu-repo/dai/nl/30483095X; Murrell, J.C.; Aspegrén, J.; McKusick, B.C.; Hellebrekers, L.J.|info:eu-repo/dai/nl/073499234

    2009-01-01

    Vet Anaesth Analg. 2009 Jul;36(4):369-83. Epub 2009 May 12. Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs. Valtolina C, Robben JH, Uilenreef J, Murrell JC, Aspegrén J, McKusick BC, Hellebrekers LJ. Department

  20. Fluorescence anisotropy-based measurement of Pseudomonas aeruginosa penicillin-binding protein 2 transpeptidase inhibitor acylation rate constants.

    Science.gov (United States)

    Shapiro, Adam B; Gao, Ning; Gu, Rong-Fang; Thresher, Jason

    2014-10-15

    High-molecular-weight penicillin-binding proteins (PBPs) are essential integral membrane proteins of the bacterial cytoplasmic membrane responsible for biosynthesis of peptidoglycan. They are the targets of antibacterial β-lactam drugs, including penicillins, cephalosporins, and carbapenems. β-Lactams covalently acylate the active sites of the PBP transpeptidase domains. Because β-lactams are time-dependent inhibitors, quantitative assessment of the inhibitory activity of these compounds ideally involves measurement of their second-order acylation rate constants. We previously described a fluorescence anisotropy-based assay to measure these rate constants for soluble constructs of PBP3 (Anal. Biochem. 439 (2013) 37-43). Here we report the expression and purification of a soluble construct of Pseudomonas aeruginosa PBP2 as a fusion protein with NusA. This soluble PBP2 was used to measure second-order acylation rate constants with the fluorescence anisotropy assay. Measurements were obtained for mecillinam, which reacts specifically with PBP2, and for several carbapenems. The assay also revealed that PBP2 slowly hydrolyzed mecillinam and was used to measure the rate constant for this deacylation reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Quantitative correlation of absolute hydroxyl radical rate constants with non-isolated effluent organic matter bulk properties in water.

    Science.gov (United States)

    Rosario-Ortiz, Fernando L; Mezyk, Stephen P; Doud, Devin F R; Snyder, Shane A

    2008-08-15

    Absolute second-order rate constants for the reaction between the hydroxyl radical (*OH) and eight water samples containing non-isolated effluent organic matter (EfOM) collected at different wastewater and reclamation sites were measured by electron pulse radiolysis. The measured rate constants ranged from 0.27 to 1.21 x 10(9) Mc(-1) s(-1), with an average value of 0.86 (+/-0.35) x 10(9) Mc(-1) s(-1). These absolute values were 3-5 times faster than previously reported values using natural organic matter and wastewater isolates. The obtained rate constants were correlated (R2 > 0.99) to bulk EfOM properties through an empirical equation that included terms relating to the polarity, apparent molecular weight, and fluorescence index of the effluent organic matter. The obtained data were used to model steady state *OH concentrations during UV advanced oxidation. The steady-state *OH concentration was lower than that obtained using previously reported values for the reaction with dissolved organic matter, indicating that accurate measurement of reaction rate constants at specific sites would greatly improve the design and prediction of the removal of organic contaminants. These results will improve the ability of researchers to accurately model scavenging capacities during the advanced oxidation processtreatment of wastewaters.

  2. AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.

    Science.gov (United States)

    Ordoñez-Gutierrez, Lara; Fernandez-Perez, Ivan; Herrera, Jose Luis; Anton, Marta; Benito-Cuesta, Irene; Wandosell, Francisco

    2016-09-06

    Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.

  3. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice.

    Science.gov (United States)

    Li, Chaoyun; Zug, Caroline; Qu, Hongchun; Schluesener, Hermann; Zhang, Zhiyuan

    2015-03-15

    In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in Alzheimer's disease and its animal models. Hesperidin, a flavanone glycoside found abundantly in citrus fruits, was orally given (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, a mouse model of cerebral amyloidosis for Alzheimer's disease. After a relatively short-term treatment of 10 days, hesperidin significantly restored deficits in non-cognitive nesting ability and social interaction. Further immunohistochemical analysis showed significantly attenuated β-amyloid deposition, plaque associated APP expression, microglial activation and TGF-β immunoreactivity in brains of APP/PS1 mice, which suggests that ameliorated behavioral impairments might be attributable to reduced Aβ deposition and attenuated neuro-inflammatory reaction. Additionally, efficient anti-inflammatory effects of hesperidin were confirmed in vitro. Our findings suggest that hesperidin might be a potential candidate for the treatment of AD or even other neurodegenerative diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Geniposide attenuates mitochondrial dysfunction and memory deficits in APP/PS1 transgenic mice.

    Science.gov (United States)

    Lv, Cui; Liu, Xiaoli; Liu, Hongjuan; Chen, Tong; Zhang, Wensheng

    2014-01-01

    Oxidative stress and mitochondrial dysfunction appear early and contribute to the disease progression in Alzheimer's disease (AD), which can be detected extensively in AD patients brains as well as in transgenic AD mice brains. Thus, treatments that result in attenuation of oxidative stress and mitochondrial dysfunction may hold potential for AD treatment. Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits anti-oxidative, antiinflammatory and other important therapeutic properties. However, whether geniposide has any protective effect on oxidative stress and mitochondrial dysfunction in AD transgenic mouse model has not yet been reported. Here, we demonstrate that intragastric administration of geniposide significantly reduces oxidative stress and mitochondrial dysfunction in addition to improving learning and memory in APP/PS1 mice. Geniposide exerts protective effects on mitochondrial dysfunction in APP/PS1 mice through suppressing the mitochondrial oxidative damage and increasing the mitochondrial membrane potential and activity of cytochrome c oxidase. These studies indicate that geniposide may attenuate memory deficits through the suppression of mitochondrial oxidative stress. Thus, geniposide may be a potential therapeutic reagent for halting and preventing AD progress.

  5. Variational transition-state theory study of the rate constant of the DMS·OH scavenging reaction by O2.

    Science.gov (United States)

    Ramírez-Anguita, Juan M; González-Lafont, Àngels; Lluch, José M

    2011-07-30

    The chemical tropospheric dimethyl sulfide (DMS, CH3SCH3) degradation involves several steps highly dependent on the environmental conditions. So, intensive efforts have been devoted during the last years to enhance the understanding of the DMS oxidation mechanism under different conditions. The reaction of DMS with OH is considered to be the most relevant process that initiates the whole oxidation process. The experimental observations have been explained by a two-channel mechanism consisting of a H-abstraction process leading to CH3S(O)CH3 and HO2 and an addition reaction leading to the DMS·OH adduct. In the presence of O2, the DMS·OH adduct is competitively scavenged increasing the contribution of the addition channel to the overall DMS oxidation. Recent experimental measurements have determined from a global fit that the rate constant of this scavenging process is independent of pressure and temperature but this rate constant cannot be directly measured. In this article, a variational transition-state theory calculation of the low- and high-pressure rate constants for the reaction between DMS·OH and O2 has been carried out as a function of temperature. Our proposal is that the slight temperature dependence of the scavenging rate constant can only be explained if the H-abstraction bottleneck is preceded by a dynamical bottleneck corresponding to the association process between the DMS·OH adduct and the O2 molecule. The agreement between the low-pressure and high-pressure rate constants confirms the experimental observations. Copyright © 2011 Wiley Periodicals, Inc.

  6. Real-time association rate constant measurement using combination tapered fiber-optic biosensor (CTFOB) dip-probes

    Science.gov (United States)

    Simmonds, Boris; Wang, Chun-Wei; Kapoor, Rakesh

    2010-02-01

    This document reports a novel method of measuring association rate constant (ka) for antibody-antigen interaction using evanescent wave-based combination tapered fiber-optic biosensor (CTFOB) dip-probes. The method was demonstrated by measuring association rate constant for bovine serum albumin (BSA) and anti-BSA antibody interaction. "Direct method" was used for detection; goat anti-BSA "capture" antibodies were immobilized on the probe surfaces while the antigen (BSA) was directly labeled with Alexa 488 dye. The probes were subsequently submerged in 3nM Labeled BSA in egg albumin (1 mg/ml). The fluorescence signal recorded was proportional to BSA anti-BSA conjugates and continuous signal was acquired suing a fiber optic spectrometer (Ocean Optics, Inc.). A 476 nm diode laser was use as an excitation source. Association constant was estimated from a plot of signal as a function of time. Measured association rate constant ka for the binding of BSA with anti-BSA at room temperature is (8.33 +/- 0.01) x 104 M-1s-1.

  7. Site-specific reaction rate constant measurements for various secondary and tertiary H-abstraction by OH radicals

    KAUST Repository

    Badra, Jihad

    2015-02-01

    Reaction rate constants for nine site-specific hydrogen atom (H) abstraction by hydroxyl radicals (OH) have been determined using experimental measurements of the rate constants of Alkane+OH→Products reactions. Seven secondary (S 20, S 21, S 22, S 30, S 31, S 32, and S 33) and two tertiary (T 100 and T 101) site-specific rate constants, where the subscripts refer to the number of carbon atoms (C) connected to the next-nearest-neighbor (N-N-N) C atom, were obtained for a wide temperature range (250-1450K). This was done by measuring the reaction rate constants for H abstraction by OH from a series of carefully selected large branched alkanes. The rate constant of OH with four different alkanes, namely 2,2-dimethyl-pentane, 2,4-dimethyl-pentane, 2,2,4-trimethyl-pentane (iso-octane), and 2,2,4,4-tetramethyl-pentane were measured at high temperatures (822-1367K) using a shock tube and OH absorption diagnostic. Hydroxyl radicals were detected using the narrow-line-width ring-dye laser absorption of the R1(5) transition of OH spectrum near 306.69nm.Previous low-temperature rate constant measurements are added to the current data to generate three-parameter rate expressions that successfully represent the available direct measurements over a wide temperature range (250-1450. K). Similarly, literature values of the low-temperature rate constants for the reaction of OH with seven normal and branched alkanes are combined with the recently measured high-temperature rate constants from our group [1]. Subsequent to that, site-specific rate constants for abstractions from various types of secondary and tertiary H atoms by OH radicals are derived and have the following modified Arrhenius expressions:. S20=8.49×10-17T1.52exp(73.4K/T)cm3molecule-1s-1(250-1450K) S21=1.07×10-15T1.07exp(208.3K/T)cm3molecule-1s-1(296-1440K) S22=2.88×10-13T0.41exp(-291.5K/T)cm3molecule-1s-1(272-1311K) S30=3.35×10-18T1.97exp(323.1K/T)cm3molecule-1s-1(250-1366K) S31=1.60×10-18T2.0exp(500.0K/T)cm3

  8. Theoretical evaluation of non-uniform skin effect on aquifer response under constant rate pumping

    Science.gov (United States)

    Chen, Chia-Shyun; Chang, Chien-Chieh

    2006-02-01

    Under field conditions, well skin may be non-uniformly distributed over the screen section. To investigate such non-uniform skin effect on aquifer response, a model is developed where the non-uniform skin effect is represented by an arbitrary piecewise continuous skin function Sk( z) imposed on the boundary of the pumping well. Wellbore storage is taken into account in the pumping well. Due to Sk( z) the model solutions are in terms of non-orthonormal functions, and the Gram-Schmidt method is employed to determine them. It is found that the wellbore flux distribution of the pumping well Qw( z, t) is inversely related to the variation of Sk( z), creating three dimensional flow in the vicinity of the pumping well. This three dimensional flow exists even when wellbore storage is absent in the pumping well, which is different from the fact that uniform skin effect can influence aquifer drawdown only when wellbore storage exists in the pumping well. However, the three dimensional flow evolves to radial flow at farther distances, where the non-uniform skin effect is transformed into a uniform one that can be represented by a constant skin factor equal to the vertical average of Sk( z) weighted by Qw( z, t). The conventional well hydraulics models of a constant skin factor can thus be used to deal with non-uniform skin problems in the radial flow regime or when vertically average drawdown is concerned.

  9. A Constant Rate of Spontaneous Mutation in DNA-Based Microbes

    Science.gov (United States)

    Drake, John W.

    1991-08-01

    In terms of evolution and fitness, the most significant spontaneous mutation rate is likely to be that for the entire genome (or its nonfrivolous fraction). Information is now available to calculate this rate for several DNA-based haploid microbes, including bacteriophages with single- or double-stranded DNA, a bacterium, a yeast, and a filamentous fungus. Their genome sizes vary by ≈6500-fold. Their average mutation rates per base pair vary by ≈16,000-fold, whereas their mutation rates per genome vary by only ≈2.5-fold, apparently randomly, around a mean value of 0.0033 per DNA replication. The average mutation rate per base pair is inversely proportional to genome size. Therefore, a nearly invariant microbial mutation rate appears to have evolved. Because this rate is uniform in such diverse organisms, it is likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs of further reducing mutation rates.

  10. PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D. [Astrophysics Research Centre, School of Maths and Physics, Queens University, Belfast BT7 1NN (United Kingdom); Huang, K. [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Mulchaey, J. S., E-mail: nsanders@cfa.harvard.edu [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); and others

    2013-05-20

    We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 Multiplication-Sign 10{sup 3} km s{sup -1}) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt {approx} 9-23 days and shows an NUV-NIR spectral energy distribution with temperature {approx}> 17 Multiplication-Sign 10{sup 3} K and a peak magnitude of M{sub z} = -18.88 {+-} 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M{sub Sun }) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208-042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits ({Sigma}{sub H{alpha}} {approx}< 2 Multiplication-Sign 10{sup -3} M{sub Sun} yr{sup -1} kpc{sup -2}). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

  11. Theoretical Prediction of Rate Constants for Hydrogen Abstraction by OH, H, O, CH3, and HO2 Radicals from Toluene.

    Science.gov (United States)

    Li, Shu-Hao; Guo, Jun-Jiang; Li, Rui; Wang, Fan; Li, Xiang-Yuan

    2016-05-26

    Hydrogen abstraction from toluene by OH, H, O, CH3, and HO2 radicals are important reactions in oxidation process of toluene. Geometries and corresponding harmonic frequencies of the reactants, transition states as well as products involved in these reactions are determined at the B3LYP/6-31G(2df,p) level. To achieve highly accurate thermochemical data for these stationary points on the potential energy surfaces, the Gaussian-4(G4) composite method was employed. Torsional motions are treated either as free rotors or hindered rotors in calculating partion functions to determine thermodynamic properties. The obtained standard enthalpies of formation for reactants and some prodcuts are shown to be in excellent agreement with experimental data with the largest error of 0.5 kcal mol(-1). The conventional transition state theory (TST) with tunneling effects was adopted to determine rate constants of these hydrogen abstraction reactions based on results from quantum chemistry calculations. To faciliate its application in kinetic modeling, the obtained rate constants are given in Arrhenius expression: k(T) = AT(n) exp(-EaR/T). The obtained reaction rate constants also agree reasonably well with available expermiental data and previous theoretical values. Branching ratios of these reactions have been determined. The present reaction rates for these reactions have been used in a toluene combustion mechanism, and their effects on some combustion properties are demonstrated.

  12. Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

    NARCIS (Netherlands)

    Slavov, Nikolai; Budnik, Bogdan A; Schwab, David; Airoldi, Edoardo M; van Oudenaarden, Alexander

    2014-01-01

    Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such

  13. Temperature dependence of the rate constant for the bimolecular recombination of Cl-2 in water—A pulse radiolysis study

    Science.gov (United States)

    Szala-Bilnik, J.; Pierscieniewska, P.; Wolszczak, M.; Swiatla-Wojcik, D.

    2014-04-01

    The rate constant for the disproportionation of Cl-2 in water has been determined for the temperature range 22-87 °C using pulse radiolysis of 0.1 M NaCl+1 mM HClO4 aqueous solution. The rate constant for the decay of Cl-2 has been found to be 2×(7.35±0.53)×108 M-1 s-1 at 22 °C (at zero ionic strength). The determined activation energy, Ea=10.89±0.37 kJ mol-1, is less than expected for diffusion-controlled reactions. A good fit to the Noyes equation (1/kobs=1/kdiff+1/kreact) has been obtained assuming the reaction step is activationless with kreact=A‧T.

  14. Equilibrium Fermi's Golden Rule Charge Transfer Rate Constants in the Condensed Phase: The Linearized Semiclassical Method vs Classical Marcus Theory.

    Science.gov (United States)

    Sun, Xiang; Geva, Eitan

    2016-05-19

    In this article, we present a comprehensive comparison between the linearized semiclassical expression for the equilibrium Fermi's golden rule rate constant and the progression of more approximate expressions that lead to the classical Marcus expression. We do so within the context of the canonical Marcus model, where the donor and acceptor potential energy surface are parabolic and identical except for a shift in both the free energies and equilibrium geometries, and within the Condon region. The comparison is performed for two different spectral densities and over a wide range of frictions and temperatures, thereby providing a clear test for the validity, or lack thereof, of the more approximate expressions. We also comment on the computational cost and scaling associated with numerically calculating the linearized semiclassical expression for the rate constant and its dependence on the spectral density, temperature, and friction.

  15. Comparison of calculated and experimentally resolved rate constants for excitation energy transfer in C-phycocyanin. 2. Trimers

    Energy Technology Data Exchange (ETDEWEB)

    Debreczeny, M.F.; Sauer, K. [Lawrence Berkeley Lab., CA (United States); Zhou, J.; Bryant, D.A. [Pennsylvania State Univ., University Park, PA (United States)

    1995-05-18

    Resolution of the absorption spectrum of the {beta}{sub 155} chromophore in C-phycocyanin (PC) trimers is achieved by comparison of the steady state absorption spectra of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3}. Comparison of the anisotropy decays of ({alpha}{sup PC}{beta}{sup PC}){sub 3} and ({alpha}{sup PC}{beta}{sup *}){sub 3} also greatly aids in the assignment of the dominant kinetic processes in PC trimers. A comparison is made of calculated Foerster rate constants for energy transfer with those rate constants resolved experimentally in the PC trimers. 35 refs.., 10 figs., 2 tabs.

  16. Comparison of calculated and experimentally resolved rate constants for excitation energy transfer in C-phycocyanin. 1. Monomers

    Energy Technology Data Exchange (ETDEWEB)

    Debreczeny, M.P.; Sauer, K. [Lawrence Berkeley Lab., CA (United States); Zhou, J.; Bryant, D.A. [Pennsylvania State Univ., University Park, PA (United States)

    1995-05-18

    Rate constants for excitation energy transfer in light-harvesting protein, C-phycocyanin (PC), in the monomeric aggregation state, isolated from the cyanobacterium cynechococcus sp. PCC 7002, are calculated, using Foerster theory and compared with the results of time-resolved fluorescence measurements. The assignments of the energy-transfer rate constants in PC monomers are confirmed here by time-resolved fluorescence anisotropy measurements of the PC monomers isolated from both the wild-type and a mutant strain (cpcB/C155S) whose PC is missing the {beta}{sub 155} chromophore. It is concluded that the Foerster model of resonant energy transfer in the weak coupling limit successfully describes the dominant energy-transfer processes in this protein in the monomeric state. 31 refs., 3 figs., 4 tabs.

  17. Absolute rate constants for the reaction of NO with a series of peroxy radicals in the gas at 295 K

    DEFF Research Database (Denmark)

    Sehested, J.; Nielsen, O.J.; Wallington, T.J.

    1993-01-01

    The rate constants for the reaction of NO with a series of peroxy radicals: CH3O2, C2H5O2, (CH3)3CCH2O2, (CH3)3CC(CH3)2CH2O2, CH2FO2, CH2ClO2, CH2BrO2, CHF2O2, CF2ClO2, CHF2CF2O2, CF3CF2O2, CFCl2CH2O2 and CF2ClCH2O2 were measured at 298 K and a total pressure of 1 atm. The rate constants were...

  18. Stability analysis of 4-species Aβaggregation model: A novel approach to obtaining physically meaningful rate constants.

    Science.gov (United States)

    Ghag, G; Ghosh, P; Mauro, A; Rangachari, V; Vaidya, A

    2013-11-01

    Protein misfolding and concomitant aggregation towards amyloid formation is the underlying biochemical commonality among a wide range of human pathologies. Amyloid formation involves the conversion of proteins from their native monomeric states (intrinsically disordered or globular) to well-organized, fibrillar aggregates in a nucleation-dependent manner. Understanding the mechanism of aggregation is important not only to gain better insight into amyloid pathology but also to simulate and predict molecular pathways. One of the main impediments in doing so is the stochastic nature of interactions that impedes thorough experimental characterization and the development of meaningful insights. In this study, we have utilized a well-known intermediate state along the amyloid- β peptide aggregation pathway called protofibrils as a model system to investigate the molecular mechanisms by which they form fibrils using stability and perturbation analysis. Investigation of protofibril aggregation mechanism limits both the number of species to be modeled (monomers, and protofibrils), as well as the reactions to two (elongation by monomer addition, and protofibril-protofibril lateral association). Our new model is a reduced order four species model grounded in mass action kinetics. Our prior study required 3200 reactions, which makes determining the reaction parameters prohibitively difficult. Using this model, along with a linear perturbation argument, we rigorously determine stable ranges of rate constants for the reactions and ensure they are physically meaningful. This was accomplished by finding the ranges in which the perturbations dieout in a five-parameter sweep, which includes the monomer and protofibril equilibrium concentrations and three of the rate constants. The results presented are a proof-of-concept method in determining meaningful rate constants that can be used as a bonafide way for determining accurate rate constants for other models involving complex

  19. Quantum wave packet calculation of reaction probabilities, cross sections, and rate constants for the C(1D) + HD reaction

    Science.gov (United States)

    Gogtas, Fahrettin; Bulut, Niyazi; Akpinar, Sinan

    The time-dependent real wave packet method has been used to study the C(1D) + HD reaction. The state-to-state and state-to-all reactive scattering probabilities for a broad range of energies are calculated at zero total angular momentum. The probabilities for J > 0 are estimated from accurately computed J = 0 probabilities by using the J-shifting approximation. The integral cross sections for a large energy range, and thermal rate constants are calculated.

  20. The H2 + CO ↔ H2CO Reaction: Rate Constants and Relevance to Hot and Dense Astrophysical Media

    Science.gov (United States)

    Vichietti, R. M.; Spada, R. F. K.; da Silva, A. B. F.; Machado, F. B. C.; Haiduke, R. L. A.

    2016-07-01

    A theoretical thermochemical and kinetic investigation of the thermal H2 + CO ↔ H2CO reaction was performed for a temperature range from 200 to 4000 K. Geometries and vibrational frequencies of reactants, product, and transition state (TS) were obtained at CCSD/cc-pVxZ (x = T and Q) levels and scaling factors were employed to consider anharmonicity effects on vibrational frequencies, zero-point energies, and thermal corrections provided by these methodologies. Enthalpies Gibbs energies, and rate constants for this reaction were determined by including a complete basis set extrapolation correction for the electronic properties calculated at CCSD(T)/cc-pVyZ (y = Q and 5) levels. Our study indicates that enthalpy changes for this reaction are highly dependent on temperature. Moreover, forward and reverse (high-pressure limit) rate constants were obtained from variational TS theory with quantum tunneling corrections. Thus, modified Arrhenius’ equations were fitted by means of the best forward and reverse rate constant values, which provide very reliable estimates for these quantities within the temperature range between 700 and 4000 K. To our knowledge, this is the first kinetic study done for the forward H2 + CO \\to H2CO process in a wide temperature range. Finally, these results can be used to explain the formaldehyde abundance in hot and dense interstellar media, possibly providing data about the physical conditions associated with H2CO masers close to massive star-forming regions.

  1. Structure-activity relationship for the estimation of OH-oxidation rate constants of carbonyl compounds in the aqueous phase

    Science.gov (United States)

    Doussin, J.-F.; Monod, A.

    2013-12-01

    In the atmosphere, one important class of reactions occurs in the aqueous phase in which organic compounds are known to undergo oxidation towards a number of radicals, among which OH radicals are the most reactive oxidants. In 2008, Monod and Doussin have proposed a new structure-activity relationship (SAR) to calculate OH-oxidation rate constants in the aqueous phase. This estimation method is based on the group-additivity principle and was until now limited to alkanes, alcohols, acids, bases and related polyfunctional compounds. In this work, the initial SAR is extended to carbonyl compounds, including aldehydes, ketones, dicarbonyls, hydroxy carbonyls, acidic carbonyls, their conjugated bases, and the hydrated form of all these compounds. To do so, only five descriptors have been added and none of the previously attributed descriptors were modified. This extension leads now to a SAR which is based on a database of 102 distinct compounds for which 252 experimental kinetic rate constants have been gathered and reviewed. The efficiency of this updated SAR is such that 58% of the rate constants could be calculated within ±20% of the experimental data and 76% within ±40% (respectively 41 and 72% for the carbonyl compounds alone).

  2. Channel specific rate constants for reactions of O(1D) with HCl and HBr

    Science.gov (United States)

    Wine, P. H.; Wells, J. R.; Ravishankara, A. R.

    1986-01-01

    The absolute rate coefficients and product yields for reactions of O(1D) with HCl(1) and HBr(2) at 287 K are presently determined by means of the time-resolved resonance fluorescence detection of O(3P) and H(2S) in conjunction with pulsed laser photolysis of O3/HX/He mixtures. Total rate coefficients for O(1D) removal are found to be, in units of 10 to the -10th cu cm/molecule per sec, k(1) = 1.50 + or - 0.18 and k(2) 1.48 + or - 0.16; the absolute accuracy of these rate coefficients is estimated to be + or - 20 percent.

  3. Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model

    Directory of Open Access Journals (Sweden)

    Jelle Praet

    2016-01-01

    Full Text Available While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization transfer contrast (MTC imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize early amyloid β (Aβ induced pathological changes. In a cross-sectional study, a comparison was made between the MT ratio of wild type (WT and APP/PS1 mice at 2, 4, 6, 8 and 24 months of age. We observed an increased MT-ratio in the cortex of 24 month old APP/PS1 mice as compared to WT mice. However, when comparing the MT-ratio of the cortex of WT mice with the MT-ratio of the APP/PS1 mice at 2, 4, 6 or 8 months of age, no significant changes could be observed. In contrast to the cortex, we consistently observed a decreased MT-ratio in the splenium of 4, 6 and 8 month old APP/PS1 mice as compared to age-matched WT mice. Lastly, the decreased MT-ratio in the splenium of APP/PS1 mice correlated to the Aβ plaque deposition, astrogliosis and microgliosis. This MT-ratio decrease did however not correlate to the myelin content. Combined, our results suggest that MTC is able to visualize early Aβ-induced changes in the splenium but not the cortex of APP/PS1 mice.

  4. Rate Constant Change of Photo Reaction of Bacteriorhodopsin Observed in Trimeric Molecular System.

    Science.gov (United States)

    Tsujiuchi, Yutaka; Masumoto, Hiroshi; Goto, Takashi

    2016-04-01

    To elucidate the time evolution of photo reaction of bacteriorhodopsin in glycerol mixed purple membrane at around 196 K under irradiation by red light, a kinetic model was constructed. The change of absorption with irradiation at times of 560 nm and 412 nm was analyzed for the purpose of determining reaction rates of photo reaction of bacteriorhodopsin and its product M intermediate. In this study it is shown that reaction rates of conversion from bacteriorhodopsin to the M intermediate can be explained by a set of linear differential equations. This model analysis concludes that bacteriorhodopsin in which constitutes a trimer unit with other two bacteriorhodopsin molecules changes into M intermediates in the 1.73 of reaction rate, in the initial step, and according to the number of M intermediate in a trimer unit, from three to one, the reaction rate of bacteriorhodopsin into M intermediates smaller as 1.73, 0.80, 0.19 which caused by influence of inter-molecular interaction between bacteriorhodopsin.

  5. Non-Constant Learning Rates in Retrospective Experience Curve Analyses and their Correlation to Deployment Programs

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Smith, Sarah J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sohn, Michael D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-07-16

    A key challenge for policy-makers and technology market forecasters is to estimate future technology costs and in particular the rate of cost reduction versus production volume. A related, critical question is what role should state and federal governments have in advancing energy efficient and renewable energy technologies? This work provides retrospective experience curves and learning rates for several energy-related technologies, each of which have a known history of federal and state deployment programs. We derive learning rates for eight technologies including energy efficient lighting technologies, stationary fuel cell systems, and residential solar photovoltaics, and provide an overview and timeline of historical deployment programs such as state and federal standards and state and national incentive programs for each technology. Piecewise linear regimes are observed in a range of technology experience curves, and public investments or deployment programs are found to be strongly correlated to an increase in learning rate across multiple technologies. A downward bend in the experience curve is found in 5 out of the 8 energy-related technologies presented here (electronic ballasts, magnetic ballasts, compact fluorescent lighting, general service fluorescent lighting, and the installed cost of solar PV). In each of the five downward-bending experience curves, we believe that an increase in the learning rate can be linked to deployment programs to some degree. This work sheds light on the endogenous versus exogenous contributions to technological innovation and highlights the impact of exogenous government sponsored deployment programs. This work can inform future policy investment direction and can shed light on market transformation and technology learning behavior.

  6. Constant Flux Proxies and Pleistocene Sediment Accumulation Rates on the Juan de Fuca Ridge in the Northeast Pacific

    Science.gov (United States)

    Middleton, J. L.; Mukhopadhyay, S.; Langmuir, C. H.; Costa, K.; McManus, J. F.; d'Almeida, M.; Huybers, P. J.; Winckler, G.

    2016-12-01

    Mass accumulation rates of marine sediments are often employed to constrain deposition rates of important proxies such as terrigenous dust, carbonate, and biogenic opal to quantitatively examine variations in continental aridity, atmospheric transport, and biologic productivity across changing climatic conditions. However, deposition rates that are estimated using traditional mass accumulation rates calculated from sediment core age models can be subject to bias from lateral sediment transport and limited age model resolution. Constant flux proxies, such as extraterrestrial helium-3 (3HeET) and excess thorium-230 (230ThXS), can be used to calculate vertical sediment accumulation rates that are independent of age model uncertainties and the effects of lateral sediment transport. While a short half-life limits analyses of 230ThXS to the past 500 ka, 3HeET is stable and could be used to constrain sedimentary fluxes during much of the Cenozoic. Despite the vast paleoceanographic potential of constant flux proxies, few studies have directly compared the behavior of 230ThXS and 3HeET using measurements from the same samples. Sediment grain size fractionation and local scavenging effects may differentially bias one or both proxy systems and complicate the interpretation of 230ThXS or 3HeET data. We will present a new record of vertical sediment accumulation rates spanning the past 600 ka in the Northeast Pacific constrained using analyses of both 3HeET and 230ThXS in two sediment cores from cruise AT26-19 on the Juan de Fuca Ridge. Such a record allows for intercomparison of both constant flux proxies in the mid-ocean ridge environment and examination of sedimentary behavior across multiple glacial cycles. The 230ThXS-derived accumulation rates typically range from 0.5 to 2 g cm-2 ka-1 over the past 450 ka, with periods of maximum deposition coinciding with glacial maxima. Preliminary results of samples analyzed with both 3HeET and 230ThXS indicate relative consistency

  7. A methodology to study cyclic debond growth at constant mode-mixity and energy release rate

    DEFF Research Database (Denmark)

    Quispitupa, Amilcar; Berggreen, Christian; Carlsson, Leif A.

    2010-01-01

    It is well known that face/core debond crack propagation is governed by the critical energy release rate (fracture toughness) and mode-mixity at the crack tip. Thus, the current study focuses on the developing of a methodology to perform fatigue crack growth experiments of debonded sandwich...... and better control of loading conditions at the crack tip will be the most relevant outcomes of using the proposed fatigue test method....... structures under well controlled cyclic energy release rate and mode-mixity. The proposed methodology uses the mixed mode bending (MMB) sandwich specimen and MMB test rig. Crack length measurements are based on an analytically available compliance expression. Accurate fatigue crack growth measurements...

  8. A Simple Formula for Local Burnup and Isotope Distributions Based on Approximately Constant Relative Reaction Rate

    Directory of Open Access Journals (Sweden)

    Cenxi Yuan

    2016-01-01

    Full Text Available A simple and analytical formula is suggested to solve the problems of the local burnup and the isotope distributions. The present method considers two extreme conditions of neutrons penetrating the fuel rod. Based on these considerations, the formula is obtained to calculate the reaction rates of 235U, 238U, and 239Pu and straightforward the local burnup and the isotope distributions. Starting from an initial burnup level, the parameters of the formula are fitted to the reaction rates given by a Monte Carlo (MC calculation. Then the present formula independently gives very similar results to the MC calculation from the starting to high burnup level but takes just a few minutes. The relative reaction rates are found to be almost independent of the radius (except (n,γ of  238U and the burnup, providing a solid background for the present formula. A more realistic examination is also performed when the fuel rods locate in an assembly. A combination of the present formula and the MC calculation is expected to have a nice balance between the numerical accuracy and time consumption.

  9. An Effective Continuum Model for the Liquid-to-Gas Phase Change in a Porous Medium Driven by Solute Diffusion: I. Constant Pressure Decline Rates

    Energy Technology Data Exchange (ETDEWEB)

    Tsimpanogiannis, Ioannis N.; Yortsos, Yanis C.

    2001-08-15

    This report, focuses on the isothermal gas phase growth from a supersaturated, slightly compressible, binary liquid in a porous medium. This is driven by mass transfer, the extent of which is controlled by the application of either a constant-rate decline of the system pressure or the withdrawal of the liquid at a constant rate. This report deals with the first process. Pressure depletion due to constant-rate liquid withdrawal is analyzed in a companion report .

  10. The effect of solvation on the radiation damage rate constants for adenine

    DEFF Research Database (Denmark)

    Milhøj, Birgitte Olai; Sauer, Stephan P. A.

    2016-01-01

    It is a well known fact, that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation we have studied the effect of different solvation models...... in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine using Density Functional Theory at the ωB97X-D/6-311++G(2df,2pd) level with the Eckart tunneling correction. The solvent, water, has been included through either the implicit...

  11. VizieR Online Data Catalog: The Pan-STARRS release 1 (PS1) Survey - DR1 (Chambers+, 2016)

    Science.gov (United States)

    Chambers, K. C.; et al.

    2017-07-01

    The Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) is a system for wide-field astronomical imaging developed and operated by the Institute for Astronomy at the University of Hawaii. Pan-STARRS1 (PS1) is the first part of Pan-STARRS to be completed and is the basis for Data Release 1 (DR1). The PS1 survey used a 1.8m telescope and its 1.4 Gigapixel camera (GPC1) to image the sky in five broadband filters (g, r, i, z, y). PS1 took approximately 370000 exposures from 2010 to 2015. The PS1 camera surveyed the sky using 5 filters: g, r, i, z, and y. The effective wavelengths (and spectral resolutions) of these 5 filters are 481nm (R=3.5), 617nm (R=4.4), 752nm (R=5.8), 866nm (R=8.3), and 962nm (R=11.6), respectively. Please refer to Table 4 in Tonry+ (2012, J/ApJ/750/99) for bandpass details. Schlafly+ (2012ApJ...756..158S) provides updated zeropoints in Table 1. In the PS1 nomenclature, Detections are sources found in a single exposure, while Objects are either collections of Detections matched across exposures, or sources found in stacked images that combine multiple epochs to produce deeper detection limits. Only Objects are included in DR1; Detections will be included in DR2. (1 data file).

  12. Motor Cortex Theta and Gamma Architecture in Young Adult APPswePS1dE9 Alzheimer Mice.

    Directory of Open Access Journals (Sweden)

    Anna Papazoglou

    Full Text Available Alzheimer's disease (AD is a multifactorial disorder leading to progressive memory loss and eventually death. In this study, an APPswePS1dE9 AD mouse model has been analyzed for motor cortex theta, beta and gamma frequency alterations using computerized 3D stereotaxic electrode positioning and implantable video-EEG radiotelemetry to perform long-term M1 recordings from both genders considering age, circadian rhythm and activity status of experimental animals. We previously demonstrated that APPswePS1dE9 mice exibit complex alterations in hippocampal frequency power and another recent investigation reported a global increase of alpha, beta and gamma power in APPswePS1dE9 in females of 16-17 weeks of age. In this cortical study in APPswePS1dE9 mice we did not observe any changes in theta, beta and particularly gamma power in both genders at the age of 14, 15, 18 and 19 weeks. Importantly, no activity dependence of theta, beta and gamma activity could be detected. These findings clearly point to the fact that EEG activity, particularly gamma power exhibits developmental changes and spatial distinctiveness in the APPswePS1dE9 mouse model of Alzheimer's disease.

  13. Using Data Assimilation Methodology to Estimate Spatially-Variable Denitrification Rate Constants in an Irrigated Agricultural Aquifer System

    Science.gov (United States)

    Bailey, R. T.; Bau, D. A.; Gates, T. K.

    2011-12-01

    With numerical models being increasingly used to assess groundwater quality through the simulation of the fate and transport of reactive solutes in aquifer systems, it has become paramount to accurately estimate parameters, such as chemical reaction rates, that govern the subsistence of these solutes in groundwater. Such an effort is required especially in models applied to regional aquifer systems, where environmental conditions vary substantially over the spatial extent. As part of an overall effort to estimate spatially-variable parameters in chemically-active aquifer systems, we present the use of a data assimilation scheme, the Ensemble Smoother (ES), to improve estimates of spatially-variable first-order kinetic denitrification rate constants within an irrigated agricultural river-aquifer system, in light of the fact that these rates often dictate the migration of nitrate (NO3) within agricultural watersheds. Based on the Kalman Filter methodology, the ES combines (or merges) together prior uncertain parameter values, associated forecast model results, and measurement data to provide an updated, corrected model state that approaches the system state from which the measurements were taken. In this study, (NO3) concentration data are used to condition the denitrification rate constants using the correlation between rate constants and groundwater (NO3) concentration as established through the reactive transport model. As a fundamental step in eventually applying the ES scheme to an aquifer system within Colorado's Lower Arkansas River Basin, we evaluate the scheme for a synthetic aquifer system with hydrologic and chemical complexities similar to the real-world system. Complexities include heterogeneously distributed hydraulic conductivity, cropping/fallowing patterns, deep percolation, canal seepage, groundwater flows to the river, heterotrophic and autotrophic denitrification simulated using a dual-Monod approach, and leaching concentrations assigned to both

  14. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    APP/PS1 mice in a behavioural paradigm addressing working memory. Conversely, the performance of Wt mice was unaffected by SAP treatment. Choline acetyltransferase activity was reduced in the hippocampus and frontal cortex following SAP treatment. The selective effect of a mild SAP lesion in APP/PS1...... mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plaque load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice...

  15. Reactions of electronically excited boron atoms. Quenching rate constants and the radiative lifetime of the 4p 2P state

    Science.gov (United States)

    Yang, Xuefeng; Dagdigian, Paul J.

    1992-12-01

    Collisional quenching and radiative decay of the 4p 2P level of the boron atom has been studied in a cell experiment, in which B atoms are prepared by 266 nm multiphoton dissociation of BBr 3 and the 4p 2P level is prepared by sequential 2-photon absorption through the 3s 2S level. A radiative lifetime of 360 ± 50 ns is derived for B (4p 2P) by extrapolation of the measured decay rates versus BBr 3 partial pressure in several Torr helium buffer gas. Bimolecular quenching rate constants were also determined for a number of atomic and molecular species from the dependence of the B (4p 2P) decay rate on the quencher gas partial pressure. The quenching rate constants for the molecular species were quite large (≈(1-2)×10 -9 molecule -1 cm 3 s -1), presumably reflecting the small B (4p 2P) ionization potential and the rapid removal of the excited state by chemical reaction.

  16. Direct measurements of the rate constants of the reactions NCN + NO and NCN + NO2 behind shock waves.

    Science.gov (United States)

    Dammeier, J; Friedrichs, G

    2011-12-22

    The high-temperature rate constants of the reactions NCN + NO and NCN + NO(2) have been directly measured behind shock waves under pseudo-first-order conditions. NCN has been generated by the pyrolysis of cyanogen azide (NCN(3)) and quantitatively detected by sensitive difference amplification laser absorption spectroscopy at a wavelength of 329.1302 nm. The NCN(3) decomposition initially yields electronically excited (1)NCN radicals, which are subsequently transformed to the triplet ground state by collision-induced intersystem crossing (CIISC). CIISC efficiencies were found to increase in the order of Ar < NO(2) < NO as the collision gases. The rate constants of the NCN + NO/NO(2) reactions can be expressed as k(NCN+NO)/(cm(3) mol(-1)s(-1)) = 1.9 × 10(12) exp[-26.3 (kJ/mol)/RT] (±7%,ΔE(a) = ± 1.6 kJ/mol, 764 K < T < 1944 K) and k(NCN+NO(2))/(cm(3) mol(-1)s(-1)) = 4.7 × 10(12) exp[-38.0(kJ/mol)/RT] (±19%,ΔE(a) = ± 3.8 kJ/mol, 704 K < T < 1659 K). In striking contrast to reported low-temperature measurements, which are dominated by recombination processes, both reaction rates show a positive temperature dependence and are independent of the total density (1.7 × 10(-6) mol/cm(3) < ρ < 7.6 × 10(-6) mol/cm(3)). For both reactions, the minima of the total rate constants occur at temperatures below 700 K, showing that, at combustion-relevant temperatures, the overall reactions are dominated by direct or indirect abstraction pathways according to NCN + NO → CN + N(2)O and NCN + NO(2) → NCNO + NO.

  17. Theoretical determination of chemical rate constants using novel time-dependent methods

    Science.gov (United States)

    Dateo, Christopher E.

    1994-01-01

    The work completed within the grant period 10/1/91 through 12/31/93 falls primarily in the area of reaction dynamics using both quantum and classical mechanical methodologies. Essentially four projects have been completed and have been or are in preparation of being published. The majority of time was spent in the determination of reaction rate coefficients in the area of hydrocarbon fuel combustion reactions which are relevant to NASA's High Speed Research Program (HSRP). These reaction coefficients are important in the design of novel jet engines with low NOx emissions, which through a series of catalytic reactions contribute to the deterioration of the earth's ozone layer. A second area of research studied concerned the control of chemical reactivity using ultrashort (femtosecond) laser pulses. Recent advances in pulsed-laser technologies have opened up a vast new field to be investigated both experimentally and theoretically. The photodissociation of molecules adsorbed on surfaces using novel time-independent quantum mechanical methods was a third project. And finally, using state-of-the-art, high level ab initio electronic structure methods in conjunction with accurate quantum dynamical methods, the rovibrational energy levels of a triatomic molecule with two nonhydrogen atoms (HCN) were calculated to unprecedented levels of agreement between theory and experiment.

  18. The role of relative rate constants in determining surface state phenomena at semiconductor-liquid interfaces.

    Science.gov (United States)

    Iqbal, Asif; Hossain, Md Sazzad; Bevan, Kirk H

    2016-10-26

    In this work, we present a theoretical study of surface state occupation statistics at semiconductor-liquid interfaces, as it pertains to the evolution of H 2 and O 2 through water splitting. Our approach combines semiclassical charge transport and electrostatics at the semiconductor-liquid junction, with a master rate equation describing surface state mediated electron/hole transfer. As a model system we have studied the TiO 2 -water junction in the absence of illumination, where it is shown that surface states might not always equilibrate with the semiconductor. Non-trivial electrostatics, for example including a shifting of the Mott-Schottky plateau in capacitive measurements, are explored when deep-level surface states partially equilibrate with the liquid. We also endeavor to explain observations of non-linearity present in Mott-Schottky plots, as they pertain to surface state occupation statistics. In general, it is intended that the results of this work will serve to further the use and development of quantitative device modeling techniques in the description of H 2 evolution at semiconductor-liquid junctions.

  19. Variational RRKM calculation of thermal rate constant for C–H bond fission reaction of nitro methane

    Directory of Open Access Journals (Sweden)

    Afshin Taghva Manesh

    2017-02-01

    Full Text Available The present work provides quantitative results for the rate constants of unimolecular C–H bond fission reactions in the nitro methane at elevated temperatures up to 2000 K. In fact, there are three different hydrogen atoms in the nitro methane. The potential energy surface for each C–H bond fission reaction of nitro methane was investigated by ab initio calculations. The geometry and vibrational frequencies of the species involved in this process were optimized at the MP2 level of theory, using the cc-pvdz basis set. Since C–H bond fission channel is a barrierless reaction, we have used variational RRKM theory to predict rate coefficients. By means of calculated rate coefficients at different temperatures, the Arrhenius expression of the channel over the temperature range of 100–2000 K is k(T = 5.9E19∗exp(−56274.6/T.

  20. Creatine kinase rate constant in the human heart measured with 3D‐localization at 7 tesla

    Science.gov (United States)

    Robson, Matthew D.; Neubauer, Stefan; Rodgers, Christopher T.

    2016-01-01

    Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27579566

  1. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  2. Non-steady state mass action dynamics without rate constants: dynamics of coupled reactions using chemical potentials

    Science.gov (United States)

    Cannon, William R.; Baker, Scott E.

    2017-10-01

    Comprehensive and predictive simulation of coupled reaction networks has long been a goal of biology and other fields. Currently, metabolic network models that utilize enzyme mass action kinetics have predictive power but are limited in scope and application by the fact that the determination of enzyme rate constants is laborious and low throughput. We present a statistical thermodynamic formulation of the law of mass action for coupled reactions at both steady states and non-stationary states. The formulation uses chemical potentials instead of rate constants. When used to model deterministic systems, the method corresponds to a rescaling of the time dependent reactions in such a way that steady states can be reached on the same time scale but with significantly fewer computational steps. The relationships between reaction affinities, free energy changes and generalized detailed balance are central to the discussion. The significance for applications in systems biology are discussed as is the concept and assumption of maximum entropy production rate as a biological principle that links thermodynamics to natural selection.

  3. An independent constraint on the secular rate of variation of the gravitational constant from pulsating white dwarfs

    Energy Technology Data Exchange (ETDEWEB)

    Córsico, Alejandro H.; Althaus, Leandro G. [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Paseo del Bosque s/n, (1900) La Plata (Argentina); García-Berro, Enrique [Departament de Física Aplicada, Universitat Politècnica de Catalunya, c/Esteve Terrades, 5, 08860 Castelldefels (Spain); Romero, Alejandra D., E-mail: acorsico@fcaglp.unlp.edu.ar, E-mail: althaus@fcaglp.unlp.edu.ar, E-mail: enrique.garcia-berro@upc.edu, E-mail: alejandra.romero@ufrgs.br [Departamento de Astronomia, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970, RS (Brazil)

    2013-06-01

    A secular variation of the gravitational constant modifies the structure and evolutionary time scales of white dwarfs. Using an state-of-the-art stellar evolutionary code and an up-to-date pulsational code we compute the effects of a secularly varying G on the pulsational properties of variable white dwarfs. Comparing the the theoretical results obtained taking into account the effects of a running G with the observed periods and measured rates of change of the periods of two well studied pulsating white dwarfs, G117-B15A and R548, we place constraints on the rate of variation of Newton's constant. We derive an upper bound Ġ/G ∼ −1.8 × 10{sup −10} yr{sup −1} using the variable white dwarf G117-B15A, and Ġ/G ∼ −1.3 × 10{sup −10} yr{sup −1} using R548. Although these upper limits are currently less restrictive than those obtained using other techniques, they can be improved in a future measuring the rate of change of the period of massive white dwarfs.

  4. Acute exercise does not modify brain activity and memory performance in APP/PS1 mice.

    Science.gov (United States)

    Miki Stein, Angelica; Munive, Victor; Fernandez, Ana M; Nuñez, Angel; Torres Aleman, Ignacio

    2017-01-01

    Age is the main risk factor for Alzheimer´s disease (AD). With an increasingly aging population, development of affordable screening techniques to determine cognitive status will help identify population-at-risk for further follow-up. Because physical exercise is known to modulate cognitive performance, we used it as a functional test of cognitive health. Mice were submitted to treadmill running at moderate speed for 30 min, and their brain activity was monitored before and after exercise using electrocorticogram (ECG) recordings. After exercise, normal, but not APP/PS1 mice, a well established AD model, showed significantly increased ECG theta rhythm. At the same time normal, but not AD mice, showed significantly enhanced performance in a spatial memory test after exercise. Therefore, we postulate that a running bout coupled to pre- and post-exercise brain activity recordings will help identify individuals with cognitive alterations, by determining the presence or absence of exercise-specific changes in brain activity. Work in humans using a bout of moderate exercise plus electroencephalography, a clinically affordable procedure, is warranted.

  5. Determination of Chemical Kinetic Rate Constants of a Model for Carbothermal Processing of Lunar Regolith Simulant Using Methane

    Science.gov (United States)

    Balasubramaniam, R; Gokoglu, S.; Hegde, U.

    2009-01-01

    We have previously developed a chemical conversion model of the carbothermal processing of lunar regolith using methane to predict the rate of production of carbon monoxide. In this carbothermal process, gaseous methane is pyrolyzed as it flows over the hot surface of a molten zone of lunar regolith and is converted to carbon and hydrogen. Hydrogen is carried away by the exiting stream of gases and carbon is deposited on the melt surface. The deposited carbon mixes with the melt and reacts with the metal oxides in it to produce carbon monoxide that bubbles out of the melt. In our model, we assume that the flux of carbon deposited is equal to the product of the surface reaction rate constant gamma and the concentration of methane adjacent to the melt surface. Similarly, the rate of consumption of carbon per unit volume in the melt is equal to the product of the melt reaction rate constant k and the concentrations of carbon and metal oxide in the melt. In this paper, we describe our effort to determine gamma and k by comparison of the predictions from our model with test data obtained by ORBITEC (Orbital Technologies Corporation). The concentration of methane adjacent to the melt surface is a necessary input to the model. It is inferred from the test data by a mass balance of methane, adopting the usual assumptions of the continuously-stirred-tank-reactor model, whereby the average concentration of a given gaseous species equals its exit concentration. The reaction rates gamma and k have been determined by a non-linear least-squares fit to the test data for the production of carbon monoxide and the fraction of the incoming methane that is converted. The comparison of test data with our model predictions using the determined chemical kinetic rate constants provides a consistent interpretation of the process over the full range of temperatures, pressures, and methane flow rates used in the tests, thereby increasing our confidence to use the model for scale-up purposes.

  6. Relation between electrical percolation and rate constant for exchange of material between droplets in water in oil microemulsions

    Energy Technology Data Exchange (ETDEWEB)

    Jada, A.; Lang, J.; Zana, R. (Institut Charles Sadron, Strasbourg (France))

    1989-01-12

    The rate constant k{sub e} associated with the exchange of material upon collisions between droplets in ternary water in oil microemulsions stabilized by ionic surfactants has been determined by a time-resolved fluorescence method. The electrical conductivity of the same systems has been investigated. It appears that percolative conduction occurs only in systems where k{sub e} is larger than (1-2) {times} 10{sup 9} M{sup {minus}1} s{sup {minus}1}. This result supports the hypothesis that above percolation threshold the conductivity is mainly due to the motion of counterions through water channels or fusion between droplets in droplet clusters.

  7. A survey of the reaction rate constants for the thermal dissociation and recombination of nitrogen and oxygen

    Science.gov (United States)

    Marraffa, Lionel; Dulikravich, George S.; Keeney, Timothy C.; Deiwert, George S.

    1988-01-01

    The objective of the present report is to survey the various values of forward and backward reaction rate constants used by investigators in the field of high-temperature (T greater than 2000 K) gas reactions involving nitrogen and oxygen only. The objective is to find those values that correlate well so that they can be used for the studies of hypersonic flow and supersonic combustion with reasonable confidence. Relatively good agreement among these various values is observed for temperatures lower than 10,000 K.

  8. Interaction of hydrated electron with dietary flavonoids and phenolic acids. Rate constants and transient spectra studied by pulse radiolysis

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Zhongli; Li, Xifeng; Katsumura, Yosuke [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab

    2000-03-01

    The reaction rate constants and transient spectra of 11 flavonoids and 4 phenolic acids reacting with e{sub aq}{sup -} at neutral pH were measured. The results suggest that C{sub 4} keto group is the active site for e{sub aq}{sup -} to attack on flavonoids and phenolic acids, while the o-dihydroxy structure in B-ring, the C{sub 2,3} double bond, the C{sub 3}-OH group and glycosylation have little effects on the e{sub aq}{sup -} scavenging activities. (author)

  9. An optimal policy for deteriorating items with time-proportional deterioration rate and constant and time-dependent linear demand rate

    Science.gov (United States)

    Singh, Trailokyanath; Mishra, Pandit Jagatananda; Pattanayak, Hadibandhu

    2017-04-01

    In this paper, an economic order quantity (EOQ) inventory model for a deteriorating item is developed with the following characteristics: (i) The demand rate is deterministic and two-staged, i.e., it is constant in first part of the cycle and linear function of time in the second part. (ii) Deterioration rate is time-proportional. (iii) Shortages are not allowed to occur. The optimal cycle time and the optimal order quantity have been derived by minimizing the total average cost. A simple solution procedure is provided to illustrate the proposed model. The article concludes with a numerical example and sensitivity analysis of various parameters as illustrations of the theoretical results.

  10. Hydroxyl-radical-induced degradative oxidation of beta-lactam antibiotics in water: absolute rate constant measurements.

    Science.gov (United States)

    Dail, Michelle K; Mezyk, Stephen P

    2010-08-19

    The beta-lactam antibiotics are some of the most prevalent pharmaceutical contaminants currently being detected in aquatic environments. Because the presence of any trace level of antibiotic in water may adversely affect aquatic ecosystems and contribute to the production of antibiotic-resistant bacteria, active removal by additional water treatments, such as using advanced oxidation and reduction processes (AO/RPs), may be required. However, to ensure that any AOP treatment process occurs efficiently and quantitatively, a full understanding of the kinetics and mechanisms of all of the chemical reactions involved under the conditions of use is necessary. In this study, we report on our kinetic measurements for the hydroxyl-radical-induced oxidation of 11 beta-lactam antibiotics obtained using electron pulse radiolysis techniques. For the 5-member ring species, an average reaction rate constant of (7.9 +/- 0.8) x 10(9) M(-1) s(-1) was obtained, slightly faster than for the analogous 6-member ring containing antibiotics, (6.6 +/- 1.2) x 10(9) M(-1) s(-1). The consistency of these rate constants for each group infers a common reaction mechanism, consisting of the partitioning of the hydroxyl radical between addition to peripheral aromatic rings and reaction with the central double-ring core of these antibiotics.

  11. Rationale choosing interval of a piecewise-constant approximation of input rate of non-stationary queue system

    Science.gov (United States)

    Korelin, Ivan A.; Porshnev, Sergey V.

    2018-01-01

    The paper demonstrates the possibility of calculating the characteristics of the flow of visitors to objects carrying out mass events passing through checkpoints. The mathematical model is based on the non-stationary queuing system (NQS) where dependence of requests input rate from time is described by the function. This function was chosen in such way that its properties were similar to the real dependencies of speed of visitors arrival on football matches to the stadium. A piecewise-constant approximation of the function is used when statistical modeling of NQS performing. Authors calculated the dependencies of the queue length and waiting time for visitors to service (time in queue) on time for different laws. Time required to service the entire queue and the number of visitors entering the stadium at the beginning of the match were calculated too. We found the dependence for macroscopic quantitative characteristics of NQS from the number of averaging sections of the input rate.

  12. The effects of molecular weight on the single lap shear creep and constant strain rate behavior of thermoplastic polyimidesulfone adhesive

    Science.gov (United States)

    Dembosky, Stanley K.; Sancaktar, Erol

    1985-01-01

    The bonded shear creep and constant strain rate behaviors of zero, one, and three percent endcapped thermoplastic polyimidesulfone adhesive were examined at room and elevated temperatures. Endcapping was accomplished by the addition of phthalic anhydrides. The primary objective was to determine the effects of molecular weight on the mechanical properties of the adhesive. Viscoelastic and nonlinear elastic constitutive equations were utilized to model the adhesive. Ludwik's and Crochet's relations were used to describe the experimental failure data. The effects of molecular weight changes on the above mentioned mechanical behavior were assessed. The viscoelastic Chase-Goldsmith and elastic nonlinear relations gave a good fit to the experimental stress strain behavior. Crochet's relations based on Maxwell and Chase-Goldsmith models were fit to delayed failure data. Ludwik's equations revealed negligible rate dependence. Ultimate stress levels and the safe levels for creep stresses were found to decrease as molecular weight was reduced.

  13. Tissue vitamin concentrations are maintained constant by changing the urinary excretion rate of vitamins in rats' restricted food intake.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2014-01-01

    We previously reported that mild food restriction induces a reduction in tryptophan-nicotinamide conversion, which helps to explain why death secondary to pellagra is pandemic during the hungry season. In this study, we investigated the levels of B-group vitamins in the liver, kidney, blood, and urine in rats that underwent gradual restriction of food intake (80, 60, 40, and 20% restriction vs. ad libitum food intake). No significant differences in the B-group vitamin concentrations (mol/g tissue) in the liver and kidney were observed at any level of food restriction. However, the urine excretion rates exhibited some characteristic phenomena that differed by vitamin. These results show that the tissue concentrations of B-group vitamins were kept constant by changing the urinary elimination rates of vitamins under various levels of food restriction. Only vitamin B12 was the only (exception).

  14. Effects of (-epicatechin on the pathology of APP/PS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Yueqin eZeng

    2014-05-01

    Full Text Available Background: Alzheimer’s disease is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The clearance of Aβ from the brain and anti-inflammation are potential important strategies to prevent and treat disease. In a previous study, we demonstrated the grape seed extract (GSE could reduce brain Aβ burden and microglia activation,but which polyphenol plays a major role in these events is not known. Here we tested pharmacological effects of (-epicatechin, one principle polyphenol compound in GSE, on transgenic AD mice.Methods: APP/PS1 transgenic mice were fed with (-epicatechin diet(40mg/kg/d and curcumin diet (47mg/kg/d at 3 months of age for 9 months, the function of liver, Aβ levels in the brain and serum, AD-type neuropathology, plasma levels of inflammatory cytokines were measured.Results: Towards the end of the experiment we found long-term feeding of (- epicatechin diet was well tolerated without fatality, changes in food consumption, body weight or liver function. (-Epicatechin significantly reduced total Aβ in brain and serum by 39% and 40%, respectively, compared with control diet. Microgliosis and astrocytosis in the brain of Alzheimer’s mice were also reduced by 38% and 35%, respectively. The (-epicatechin diet did not alter learning and memory behaviors in AD mice.Conclusions: This study has provided evidence on the beneficial role of (-epicatechin in ameliorating amyloid-induced AD-like pathology in AD mice, but the impact of (-epicatechin on tau pathology is not clear, also the mechanism needs further research.

  15. Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

    Science.gov (United States)

    Cheng, David; Low, Jac Kee; Logge, Warren; Garner, Brett; Karl, Tim

    2014-08-01

    Patients suffering from Alzheimer's disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage. The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents. Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze. Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours. This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.

  16. Encapsulated VEGF-secreting cells enhance proliferation of neuronal progenitors in the hippocampus of AβPP/Ps1 mice.

    Science.gov (United States)

    Antequera, Desiree; Portero, Aitziber; Bolos, Marta; Orive, Gorka; Hernández, Rosa M Rm A; Pedraz, José Luis; Carro, Eva

    2012-01-01

    Vascular endothelial growth factor (VEGF) promotes neurogenesis in the adult hippocampus, but the way in which this process occurs in the Alzheimer's disease (AD) brain is still unknown. We examined the proliferation of neuronal precursors with an ex vivo approach, using encapsulated VEGF secreting cells, in AβPP/PS1 mice, a mouse model of AD. Overexpression of VEGF and VEGF receptor flk-1 was observed in the cerebral cortex from VEGF microcapsules-treated AβPP/PS1 mice at 1, 3 and 6 months after VEGF-microcapsule implantation. Stereological counting of 5-bromodeoxyuridine positive cells revealed that encapsulated VEGF secreting cells significantly enhanced cellular proliferation in the hippocampal dentate gyrus (DG). The number of neuronal precursors in VEGF microcapsules-treated AβPP/PS1 mice was also greater, and this effect remains after 6 months. We also confirmed that encapsulated VEGF secreting cells also stimulated angiogenesis in the cerebral cortex and hippocampal dentate gyrus. In addition, we found that VEGF-microcapsule treatment was associated with a depressed expression and activity of acetylcholinesterase in the hippocampus of AβPP/PS1 mice, a similar pattern as first-line medications for the treatment of AD. We conclude that stereologically-implanted VEGF-microcapsules exert an acute and long-standing neurotrophic effects, and could be utilized to improve potential therapies to control the progression of AD.

  17. Photo-fermentational hydrogen production of Rhodobacter sp. KKU-PS1 isolated from an UASB reactor

    Directory of Open Access Journals (Sweden)

    Thitirut Assawamongkholsiri

    2015-05-01

    Conclusions: KKU-PS1 can produce hydrogen from at least 8 types of organic acids. By optimizing pH and temperature, a maximal hydrogen production by this strain was obtained. Additionally, by optimizing the light intensity, Rm was increased by approximately two fold and the lag phase of hydrogen production was shortened.

  18. The Multicenter Aerobic Iron Respiratory Chain of Acidithiobacillus ferrooxidans Functions as an Ensemble with a Single Macroscopic Rate Constant.

    Science.gov (United States)

    Li, Ting-Feng; Painter, Richard G; Ban, Bhupal; Blake, Robert C

    2015-07-24

    Electron transfer reactions among three prominent colored proteins in intact cells of Acidithiobacillus ferrooxidans were monitored using an integrating cavity absorption meter that permitted the acquisition of accurate absorbance data in suspensions of cells that scattered light. The concentrations of proteins in the periplasmic space were estimated to be 350 and 25 mg/ml for rusticyanin and cytochrome c, respectively; cytochrome a was present as one molecule for every 91 nm(2) in the cytoplasmic membrane. All three proteins were rapidly reduced to the same relative extent when suspensions of live bacteria were mixed with different concentrations of ferrous ions at pH 1.5. The subsequent molecular oxygen-dependent oxidation of the multicenter respiratory chain occurred with a single macroscopic rate constant, regardless of the proteins' in vitro redox potentials or their putative positions in the aerobic iron respiratory chain. The crowded electron transport proteins in the periplasm of the organism constituted an electron conductive medium where the network of protein interactions functioned in a concerted fashion as a single ensemble with a standard reduction potential of 650 mV. The appearance of product ferric ions was correlated with the reduction levels of the periplasmic electron transfer proteins; the limiting first-order catalytic rate constant for aerobic respiration on iron was 7,400 s(-1). The ability to conduct direct spectrophotometric studies under noninvasive physiological conditions represents a new and powerful approach to examine the extent and rates of biological events in situ without disrupting the complexity of the live cellular environment. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Multicenter Aerobic Iron Respiratory Chain of Acidithiobacillus ferrooxidans Functions as an Ensemble with a Single Macroscopic Rate Constant*

    Science.gov (United States)

    Li, Ting-Feng; Painter, Richard G.; Ban, Bhupal; Blake, Robert C.

    2015-01-01

    Electron transfer reactions among three prominent colored proteins in intact cells of Acidithiobacillus ferrooxidans were monitored using an integrating cavity absorption meter that permitted the acquisition of accurate absorbance data in suspensions of cells that scattered light. The concentrations of proteins in the periplasmic space were estimated to be 350 and 25 mg/ml for rusticyanin and cytochrome c, respectively; cytochrome a was present as one molecule for every 91 nm2 in the cytoplasmic membrane. All three proteins were rapidly reduced to the same relative extent when suspensions of live bacteria were mixed with different concentrations of ferrous ions at pH 1.5. The subsequent molecular oxygen-dependent oxidation of the multicenter respiratory chain occurred with a single macroscopic rate constant, regardless of the proteins' in vitro redox potentials or their putative positions in the aerobic iron respiratory chain. The crowded electron transport proteins in the periplasm of the organism constituted an electron conductive medium where the network of protein interactions functioned in a concerted fashion as a single ensemble with a standard reduction potential of 650 mV. The appearance of product ferric ions was correlated with the reduction levels of the periplasmic electron transfer proteins; the limiting first-order catalytic rate constant for aerobic respiration on iron was 7,400 s−1. The ability to conduct direct spectrophotometric studies under noninvasive physiological conditions represents a new and powerful approach to examine the extent and rates of biological events in situ without disrupting the complexity of the live cellular environment. PMID:26041781

  20. Bevacizumab reduces the growth rate constants of renal carcinomas: a novel algorithm suggests early discontinuation of bevacizumab resulted in a lack of survival advantage.

    Science.gov (United States)

    Stein, Wilfred D; Yang, James; Bates, Susan E; Fojo, Tito

    2008-10-01

    To hasten cancer drug development, new paradigms are needed to assess therapeutic efficacy. In a randomized phase II study in patients with renal cell carcinoma, 10 microg/kg bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) administered every 2 weeks resulted in a longer time to progression but a statistically significant difference in overall survival could not be demonstrated. We developed a novel two-phase equation to estimate concomitant rates of tumor regression (regression rate constant) and tumor growth (growth rate constant). This method allows us to assess therapeutic efficacy using tumor measurements gathered while a patient receives therapy in a clinical trial. The growth rate constants of renal cell carcinomas were significantly lower during therapy with 10 microg/kg bevacizumab than those of tumors in patients receiving placebo. In all cohorts the tumor growth rate constants were correlated with survival. That a survival advantage was not demonstrated with bevacizumab appears to have been a result of early discontinuation of bevacizumab. Single-agent bevacizumab significantly affects the growth rate constants of renal cell carcinoma. Extrapolating from the growth rate constants, we conclude that the failure to demonstrate a survival advantage in the original study was a result of premature discontinuation of bevacizumab. The mathematical model described herein has applications to many tumor types and should aid in evaluating the relative efficacies of different therapies. Quantitating tumor growth rate constants using data gathered while patients are enrolled in a clinical trial, as in the present study, may streamline and assist in drug development.

  1. Growing evidence that SNe Iax are not a one-parameter family. The case of PS1-12bwh

    Science.gov (United States)

    Magee, M. R.; Kotak, R.; Sim, S. A.; Wright, D.; Smartt, S. J.; Berger, E.; Chornock, R.; Foley, R. J.; Howell, D. A.; Kaiser, N.; Magnier, E. A.; Wainscoat, R.; Waters, C.

    2017-05-01

    In this study, we present observations of a type Iax supernova, PS1-12bwh, discovered during the Pan-STARRS1 3π-survey. Our analysis was driven by previously unseen pre-maximum, spectroscopic heterogeneity. While the light curve and post-maximum spectra of PS1-12bwh are virtually identical to those of the well-studied type Iax supernova, SN 2005hk, the -2 day spectrum of PS1-12bwh does not resemble SN 2005hk at a comparable epoch; instead, we found it to match a spectrum of SN 2005hk taken over a week earlier (-12 day). We are able to rule out the cause as being incorrect phasing, and argue that it is not consistent with orientation effects predicted by existing explosion simulations. To investigate the potential source of this difference, we performed radiative transfer modelling of both supernovae. We found that the pre-maximum spectrum of PS1-12bwh is well matched by a synthetic spectrum generated from a model with a lower density in the high velocity (≳6000 km s-1) ejecta than SN 2005hk. The observed differences between SN 2005hk and PS1-12bwh may therefore be attributed primarily to differences in the high velocity ejecta alone, while comparable densities for the lower velocity ejecta would explain the nearly identical post-maximum spectra. These two supernovae further highlight the diversity within the SNe Iax class, as well as the challenges in spectroscopically identifying and phasing these objects, especially at early epochs.

  2. Isoflurane anesthesia exacerbates learning and memory impairment in zinc-deficient APP/PS1 transgenic mice.

    Science.gov (United States)

    Feng, Chunsheng; Liu, Ya; Yuan, Ye; Cui, Weiwei; Zheng, Feng; Ma, Yuan; Piao, Meihua

    2016-12-01

    Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1.4% isoflurane exposure for 2 h on learning and memory function, and neuropathogenesis in 10-month-old Zn-adequate, Zn-deficient, and Zn-treated APP/PS1 mice with the following parameters: behavioral tests, neuronal apoptosis, Aβ, and tau pathology. The results demonstrated that isoflurane exposure showed no impact on learning and memory function, but induced transient elevation of neuroapoptosis in Zn-adequate APP/PS1 mice. Exposure of isoflurane exhibited significant neuroapoptosis, Aβ generation, tau phosphorylation, and learning and memory impairment in APP/PS1 mice in the presence of Zn deficiency. Appropriate Zn treatment improved learning and memory function, and prevented isoflurane-induced neuroapoptosis in APP/PS1 mice. Isoflurane exposure may cause potential neurotoxicity, which is tolerated to some extent in Zn-adequate APP/PS1 mice. When this tolerance is limited, like in AD with Zn deficiency, isoflurane exposure markedly exacerbated learning and memory impairment, and neuropathology, indicating that AD patients with certain conditions such as Zn deficiency may be vulnerable to volatile anesthetic isoflurane. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model.

    Science.gov (United States)

    Park, Tae-Shin; Ryu, Young-Kyoung; Park, Hye-Yeon; Kim, Jae Yun; Go, Jun; Noh, Jung-Ran; Kim, Yong-Hoon; Hwang, Jung Hwan; Choi, Dong-Hee; Oh, Won-Keun; Lee, Chul-Ho; Kim, Kyoung-Shim

    2017-01-01

    Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid β (Aβ)deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNF‑α), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aβ and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.

  4. Receptor-associated protein (RAP plays a central role in modulating Abeta deposition in APP/PS1 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Guilian Xu

    Full Text Available BACKGROUND: Receptor associated protein (RAP functions in the endoplasmic reticulum (ER to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP and lipoprotein receptor 11 (SorLA/LR11. Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP, including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9 were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-/RAP(+/- mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis.

  5. SU-F-T-33: Air-Kerma Strength and Dose Rate Constant by the Full Monte Carlo Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, S [Kawasaki Medical School, Kurashiki, Okayama (Japan); Oita, M [Graduate School of Health Sciences, Okayama University, Okayama, Okayama (Japan); Narihiro, N [Kawasaki College of Allied Health Professions, Kurashiki, Okayama (Japan)

    2016-06-15

    Purpose: In general, the air-kerma strength (Sk) has been determined by the energy weighting the photon energy fluence and the corresponding mass-energy absorption coefficient or mass-energy transfer coefficient. Kerma is an acronym for kinetic energy released per unit mass, defined as the sum of the initial kinetic energies of all the charged particles. Monte Carlo (MC) simulations can investigate the kinetic energy of the charged particles after photo interactions and sum the energy. The Sk of {sup 192}Ir source is obtained in the full MC simulation and finally the dose rate constant Λ is determine. Methods: MC simulations were performed using EGS5 with the microSelectron HDR v2 type of {sup 192}Ir source. The air-kerma rate obtained to sum the electron kinetic energy after photoelectric absorption or Compton scattering for transverse-axis distance from 1 to 120 cm with a 10 m diameter air phantom. Absorbed dose in water is simulated with a 30 cm diameter water phantom. The transport cut-off energy is 10 keV and primary photons from the source need two hundred and forty billion in the air-kerma rate and thirty billion in absorbed dose in water. Results: Sk is multiplied by the square of the distance in air-kerma rate and determined by fitting a linear function. The result of Sk is (2.7039±0.0085)*10-{sup −11} µGy m{sup 2} Bq{sup −1} s{sup −1}. Absorbed dose rate in water at 1 cm transverse-axis distance D(r{sub 0}, θ{sub 0}) is (3.0114±0.0015)*10{sup −11} cGy Bq{sup −1} s{sup −1}. Conclusion: From the results, dose rate constant Λ of the microSelectron HDR v2 type of {sup 192}Ir source is (1.1137±0.0035) cGy h{sup −1} U{sup −1} by the full MC simulations. The consensus value conΛ is (1.109±0.012) cGy h{sup −1} U{sup −1}. The result value is consistent with the consensus data conΛ.

  6. The power of size. 2. Rate constants and equilibrium ratios for accumulation of inorganic substances related to species weight.

    Science.gov (United States)

    Hendriks, A J; Heikens, A

    2001-07-01

    Most of the thousands of substances and species that risk assessment has to deal with are not investigated empirically because of financial, practical, and ethical constraints. To facilitate extrapolation, we have developed a model for concentration kinetics of inorganic substances as a function of the exposure concentration of the chemical and the weight and trophic level of the species. The ecological parameters and the resistances that substances encounter during diffusion in water layers were obtained from previous reviews. The other chemical parameters (the resistances for permeation of lipid layers) were calibrated in the present study on 1,062 rate constants for absorption from water, for assimilation from food, and for elimination. Data on all elements and species were collected, but most applied to aquatic species, in particular mollusks and fish, and to transition metals, in particular group IIB (Zn, Cd, Hg). Their ratio was validated on 92 regressions and nine geometric averages, representing thousands of (near-)equilibrium accumulation ratios from laboratory and field studies. Rate constants for absorption and elimination decreased with species weight at an exponent of about -0.25, known from ecological allometry. On average, uptake-rate constants decreased with about the reciprocal square root of the exposure concentration. About 71 and 30% of the variation in absorption and elimination was explained by the model, respectively. The efficiency for assimilation of elements from food appeared to be determined mainly by the food digestibility and the distribution over egested and digested fractions. (Near-)equilibrium accumulation and magnification ratios also decreased with the reciprocal square root of the exposure concentration. The level of the organism-solids concentrations ratios roughly varied between one and two orders of magnitude, depending on the number of elements and species groups investigated. Metal concentrations did not increase at higher

  7. Creatine kinase rate constant in the human heart measured with 3D-localization at 7 tesla.

    Science.gov (United States)

    Clarke, William T; Robson, Matthew D; Neubauer, Stefan; Rodgers, Christopher T

    2017-07-01

    We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1 H localization). BOAST kfCK values were 0.281 ± 0.002 s-1 in the calf and 0.35 ± 0.05 s-1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg-1 s-1 . The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  8. Temperature dependence of the rate constant and product channels for the BrO + ClO reaction

    OpenAIRE

    Hills, AJ; Cicerone, RJ; Calvert, JG; Birks, JW

    1988-01-01

    We have measured the rate constant for the reactions BrO + ClO → Br + OClO (6a), BrO + ClO → Br + Cl + O 2 (6b), and BrO + ClO → BrCl + O 2 (6c) over the temperature range 241-408 K and found k 6 = (8.2 ± 1.0) × 10 -12 cm 3 molecule -1 s independent of temperature. Measurement of the individual product branching ratios yielded values for channels 6a, 6b, and 6c equal to 0.55 ± 0.10, 0.45 ± 0.10, and < 0.02, respectively. Measurements of ozone in the stratosphere over Antarctica have s...

  9. Temperature dependence of the rate constant for reactions of hydrated electrons with H, OH and H2O2

    DEFF Research Database (Denmark)

    Christensen, H.; Sehested, K.; Løgager, T.

    1994-01-01

    The temperature dependence of the rate constants, for the reactions of hydrated electrons with H atoms, OH radicals and H2O2 has been determined. The reaction with H atoms, studied in the temperature range 20-250-degrees-C gives k(20-degrees-C) = 2.4 x 10(10) M-1 s-1 and the activation energy E...... of hydrated electron with H2PO4- was determined to k(20-degrees-C) = 1.5 x 10(7) M-1 s-1 and E(A) = 7.4 kJ mol-1 (1.8 kcal mol-1) in the temperature range 20-200-degrees-C....

  10. Water Exchange Rate Constant as a Biomarker of Treatment Efficacy in Patients With Brain Metastases Undergoing Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Mehrabian, Hatef, E-mail: hatef.mehrabian@sri.utoronto.ca [Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Desmond, Kimberly L. [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Chavez, Sofia [Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario (Canada); Bailey, Colleen [Computer Science Department, University College London, London (United Kingdom); Rola, Radoslaw [Neurosurgery and Pediatric Neurosurgery, Medical University, Lublin (Poland); Sahgal, Arjun [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Czarnota, Gregory J. [Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Soliman, Hany [Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Martel, Anne L. [Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Stanisz, Greg J. [Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Neurosurgery and Pediatric Neurosurgery, Medical University, Lublin (Poland)

    2017-05-01

    Purpose: This study was designed to evaluate whether changes in metastatic brain tumors after stereotactic radiosurgery (SRS) can be seen with quantitative MRI early after treatment. Methods and Materials: Using contrast-enhanced MRI, a 3-water-compartment tissue model consisting of intracellular (I), extracellular-extravascular (E), and vascular (V) compartments was used to assess the intra–extracellular water exchange rate constant (k{sub IE}), efflux rate constant (k{sub ep}), and water compartment volume fractions (M{sub 0,I}, M{sub 0,E}, M{sub 0,V}). In this prospective study, 19 patients were MRI-scanned before treatment and 1 week and 1 month after SRS. The change in model parameters between the pretreatment and 1-week posttreatment scans was correlated to the change in tumor volume between pretreatment and 1-month posttreatment scans. Results: At 1 week k{sub IE} differentiated (P<.001) tumors that had partial response from tumors with stable and progressive disease, and a high correlation (R=−0.76, P<.001) was observed between early changes in the k{sub IE} and tumor volume change 1 month after treatment. Other model parameters had lower correlation (M{sub 0,E}) or no correlation (k{sub ep}, M{sub 0,V}). Conclusions: This is the first study that measured k{sub IE} early after SRS, and it found that early changes in k{sub IE} (1 week after treatment) highly correlated with long-term tumor response and could predict the extent of tumor shrinkage at 1 month after SRS.

  11. Combination of poroelasticity theory and constant strain rate test in modelling land subsidence due to groundwater extraction

    Science.gov (United States)

    Pham, Tien Hung; Rühaak, Wolfram; Sass, Ingo

    2017-04-01

    Extensive groundwater extraction leads to a drawdown of the ground water table. Consequently, soil effective stress increases and can cause land subsidence. Analysis of land subsidence generally requires a numerical model based on poroelasticity theory, which was first proposed by Biot (1941). In the review of regional land subsidence accompanying groundwater extraction, Galloway and Burbey (2011) stated that more research and application is needed in coupling of stress-dependent land subsidence process. In geotechnical field, the constant rate of strain tests (CRS) was first introduced in 1969 (Smith and Wahls 1969) and was standardized in 1982 through the designation D4186-82 by American Society for Testing and Materials. From the reading values of CRS tests, the stress-dependent parameters of poroelasticity model can be calculated. So far, there is no research to link poroelasticity theory with CRS tests in modelling land subsidence due to groundwater extraction. One dimensional CRS tests using conventional compression cell and three dimension CRS tests using Rowe cell were performed. The tests were also modelled by using finite element method with mixed elements. Back analysis technique is used to find the suitable values of hydraulic conductivity and bulk modulus that depend on the stress or void ratio. Finally, the obtained results are used in land subsidence models. Biot, M. A. (1941). "General theory of three-dimensional consolidation." Journal of applied physics 12(2): 155-164. Galloway, D. L. and T. J. Burbey (2011). "Review: Regional land subsidence accompanying groundwater extraction." Hydrogeology Journal 19(8): 1459-1486. Smith, R. E. and H. E. Wahls (1969). "Consolidation under constant rates of strain." Journal of Soil Mechanics & Foundations Div.

  12. Other paradigms: growth rate constants and tumor burden determined using computed tomography data correlate strongly with the overall survival of patients with renal cell carcinoma.

    Science.gov (United States)

    Stein, Wilfred D; Huang, Hui; Menefee, Michael; Edgerly, Maureen; Kotz, Herb; Dwyer, Andrew; Yang, James; Bates, Susan E

    2009-01-01

    In solid tumors, where curative therapies still elude oncologists, novel paradigms are needed to assess the efficacy of new therapies and those already approved. We used radiologic measurements obtained in patients with metastatic renal cell carcinoma enrolled in a phase II study of the epothilone B analog, ixabepilone (Ixempra), to address this issue. Using a novel 2-phase mathematical equation, we used the radiologic measurements to estimate the concomitant rates of tumor regression and growth (regression and growth rate constants). Eighty-one patients were enrolled on the ixabepilone trial at the time of this analysis. Growth rate constants were determined using computed tomography measurements obtained exclusively while a patient was enrolled on study. The growth rate constants of renal cell carcinomas treated with ixabepilone were significantly reduced compared with those of tumors in patients who received placebo in a previous trial. Furthermore, a correlation with overall survival was found for both the growth rate constant and the initial tumor burden; and this correlation was even stronger when both the growth rate constant and the initial tumor burden were combined. The readily amenable mathematical model described herein has potential applications to many tumor types that can be assessed with imaging modalities. Because the growth rate constant seems to be a surrogate for survival, assessment could aid in the evaluation of relative efficacies of different therapies and perhaps in assessing the potential individual benefit of an experimental therapy.

  13. ESTIMATION OF HYDROLYSIS RATE CONSTANTS OF CARBOXYLIC ACID ESTER AND PHOSPHATE ESTER COMPOUNDS IN AQUEOUS SYSTEMS FROM MOLECULAR STRUCTURE BY SPARC

    Science.gov (United States)

    SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate hydrolysis rate constants for carboxylic acid ester and phosphate ester compounds in aqueous non- aqueous and systems strictly from molecular structure. The energy diffe...

  14. Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Ilkjær, Laura; Clausen, Bettina H

    2015-01-01

    Beta-amyloid (Aβ) plaques and chronic neuroinflammation are significant neuropathological features of Alzheimer's disease. Microglial cells in aged brains have potential to produce cytokines such as TNF and IL-1 family members (IL-1α, IL-1β, and IL-1Ra) and to phagocytose Aβ in Alzheimer's disease...... of CD11b, TNF, and IL-1Ra. Cytokine production and Aβ load were assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas most microglia in aged mice produced IL-1Ra, relatively low proportions of microglia produced TNF, IL-1α, and IL-1β. However, microglial production...... of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia that phagocytosed endogenously-produced Aβ were only observed in APP/PS1 Tg mice. Differences in phagocytic index and total Aβ load were observed in microglia with specific cytokine profiles. Both phagocytic index and total Aβ load...

  15. VizieR Online Data Catalog: Gaia-PS1-SDSS (GPS1) proper motion catalog (Tian+, 2017)

    Science.gov (United States)

    Tian, H.-J.; Gupta, P.; Sesar, B.; Rix, H.-W.; Martin, N. F.; Liu, C.; Goldman, B.; Platais, I.; Kudritzki, R.-P.; Waters, C. Z.

    2018-02-01

    In order to construct proper motions, we analyze and model catalog positions from four different imaging surveys, as discussed below. Gaia DR1 is based on observations collected between 2014 July 25 and 2015 September 16. PS1 observations were collected between 2010 and 2014. The SDSS DR9 data used here were obtained in the years between 2000 and 2008. The images from 2MASS were taken between 1997 and 2001. (1 data file).

  16. Functional autoradiography shows unaltered cannabinoid CB1 receptor signalling in hippocampus and cortex of APP/PS1 transgenic mice.

    Science.gov (United States)

    Kärkkäine, E; Tanila, H; Laitinen, J T

    2012-12-01

    The cannabinoid CB1-receptor is among the most abundant G-protein-coupled receptors in the mammalian brain. Whereas post-mortem studies in Alzheimer's disease (AD) brains compared to age-matched controls have reported decreased CB1-receptor binding but no change in their protein levels (immunoreactivity), decreased or increased CB1- receptor protein levels have been reported in APP/PS1 transgenic mice modelling AD. To complete the picture, the present study used functional autoradiography to assess CB1-receptor-dependent G(i) protein activation in the hippocampus, entorhinal cortex and medial frontal cortex of 13- to 14-month-old female APPswe/PS1dE9 transgenic and wild-type littermate control mice. The mouse brains were processed for [³⁵S]GTPλS autoradiography so that brain sections were analysed in pairs of one transgenic and one control mouse brain. The autoradiography protocol was completed for each pair both in the absence and presence of dithiotreitol (DTT) to reveal possible redox-dependent alterations in CB1 receptor function. Five treatments were used: baseline, incubation with 10 μM GTPλS to assess nonspecific binding, and CB1 receptor agonist CP55,940 in three concentrations. By and large we found no statistically significant differences between the APP/PS1 transgenic and control mice in CB1 receptor signalling. The only exception was a modest redox-dependent alteration in entorhinal cortical CB1 receptors between the genotypes. Thus, in accordance with the majority of earlier human AD findings, we did not find evidence for notable changes in the number of functional CB1 receptors in the common APPswe/PS1dE9 mouse model of AD.

  17. Mitochondrial dynamics changes with age in an APPsw/PS1dE9 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Xu, Lin-Lin; Shen, Yang; Wang, Xiao; Wei, Li-Fei; Wang, Ping; Yang, Hui; Wang, Cun-Fu; Xie, Zhao-Hong; Bi, Jian-Zhong

    2017-03-01

    Increasing research suggests that mitochondrial defects play a major role in Alzheimer's disease (AD) pathogenesis. We aimed to better understand changes in mitochondria with the development and progression of AD. We compared APPsw/PS1dE9 transgenic mice at 3, 6, 9, and 12 months old as an animal model of AD and age-matched C57BL/6 mice as controls. The learning ability and spatial memory ability of APPsw/PS1dE9 mice showed significant differences compared with controls until 9 and 12 months. Mitochondrial morphology was altered in hippocampus tissue of APPsw/PS1dE9 mice beginning from the third month. 'Medullary corpuscle', which is formed by the accumulation of a large amount of degenerative and fragmented mitochondria in neuropils, may be the characteristic change observed on electron microscopy at a late stage of AD. Moreover, levels of mitochondrial fusion proteins (optic atrophy 1 and mitofusin 2) and fission proteins (dynamin-related protein 1 and fission 1) were altered in transgenic mice compared with controls with progression of AD. We found increased levels of fission and fusion proteins in APP/PS1 mice at 3 months, indicating that the presence of abnormal mitochondrial dynamics may be events in early AD progression. Changes in mitochondrial preceded the onset of memory decline as measured by the modified Morris water maze test. Abnormal mitochondrial dynamics could be a marker for early diagnosis of AD and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in AD.

  18. A Gaia-PS1-SDSS (GPS1) Proper Motion Catalog Covering 3/4 of the Sky

    Science.gov (United States)

    Tian, Hai-Jun; Gupta, Prashansa; Sesar, Branimir; Rix, Hans-Walter; Martin, Nicolas F.; Liu, Chao; Goldman, Bertrand; Platais, Imants; Kudritzki, Rolf-Peter; Waters, Christopher Z.

    2017-09-01

    We combine Gaia DR1, PS1, Sloan Digital Sky Survey (SDSS), and 2MASS astrometry to measure proper motions for 350 million sources across three-fourths of the sky down to a magnitude of {m}r˜ 20. Using positions of galaxies from PS1, we build a common reference frame for the multi-epoch PS1, single-epoch SDSS and 2MASS data, and calibrate the data in small angular patches to this frame. As the Gaia DR1 excludes resolved galaxy images, we choose a different approach to calibrate its positions to this reference frame: we exploit the fact that the proper motions of stars in these patches are linear. By simultaneously fitting the positions of stars at different epochs of—Gaia DR1, PS1, SDSS, and 2MASS—we construct an extensive catalog of proper motions dubbed GPS1. GPS1 has a characteristic systematic error of less than 0.3 {mas} {{yr}}-1 and a typical precision of 1.5-2.0 {mas} {{yr}}-1. The proper motions have been validated using galaxies, open clusters, distant giant stars, and QSOs. In comparison with other published faint proper motion catalogs, GPS1's systematic error ( 2.0 {mas} {{yr}}-1). Similarly, its precision (˜1.5 {mas} {{yr}}-1) is a four-fold improvement relative to PPMXL and UCAC4 (˜6.0 {mas} {{yr}}-1). For QSOs, the precision of GPS1 is found to be worse (˜2.0-3.0 {mas} {{yr}}-1), possibly due to their particular differential chromatic refraction. The GPS1 catalog will be released online and be available via the VizieR Service and VO Service.

  19. Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Takara, L.S.; Cunha, T.M.; Barbosa, P.; Rodrigues, M.K.; Oliveira, M.F.; Nery, L.E. [Setor de Função Pulmonar e Fisiologia Clínica do Exercício, Disciplina de Pneumologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Neder, J.A. [Setor de Função Pulmonar e Fisiologia Clínica do Exercício, Disciplina de Pneumologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen' s University, Kingston, ON (Canada)

    2012-10-15

    This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V{sub CW}) = rib cage (V{sub RC}) + abdomen (V{sub AB})] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III) underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim) at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE) V{sub CW} increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V{sub CW} regulation as EEV{sub CW} increased non-linearly in 17/30 “hyperinflators” and decreased in 13/30 “non-hyperinflators” (P < 0.05). EEV{sub AB} decreased slightly in 8 of the “hyperinflators”, thereby reducing and slowing the rate of increase in end-inspiratory (EI) V{sub CW} (P < 0.05). In contrast, decreases in EEV{sub CW} in the “non-hyperinflators” were due to the combination of stable EEV{sub RC} with marked reductions in EEV{sub AB}. These patients showed lower EIV{sub CW} and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05). Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV{sub CW} regardless of the presence or absence of dynamic hyperinflation (P < 0.001). However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid) their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.

  20. Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    L.S. Takara

    2012-12-01

    Full Text Available This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V CW = rib cage (V RC + abdomen (V AB] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE V CW increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V CW regulation as EEV CW increased non-linearly in 17/30 "hyperinflators" and decreased in 13/30 "non-hyperinflators" (P < 0.05. EEV AB decreased slightly in 8 of the "hyperinflators", thereby reducing and slowing the rate of increase in end-inspiratory (EI V CW (P < 0.05. In contrast, decreases in EEV CW in the "non-hyperinflators" were due to the combination of stable EEV RC with marked reductions in EEV AB. These patients showed lower EIV CW and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05. Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV CW regardless of the presence or absence of dynamic hyperinflation (P < 0.001. However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.

  1. SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R; Wang, J [Peking University Third Hospital, Beijing, Beijing (China)

    2014-06-01

    Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)

  2. Rate constants and branching ratios for the reaction of CH radicals with NH3: a combined experimental and theoretical study.

    Science.gov (United States)

    Blitz, Mark A; Talbi, Dahbia; Seakins, Paul W; Smith, Ian W M

    2012-06-21

    The reaction between CH radicals and NH(3) molecules is known to be rapid down to at least 23 K {at which temperature k = (2.21 ± 0.17) × 10(-10) cm(3) molecule(-1) s(-1): Bocherel ; et al. J. Phys. Chem. 1996, 100, 3063}. However, there have been only limited theoretical investigations of this reaction and its products are not known. This paper reports (i) ab initio quantum chemical calculations on the energy paths that lead to various reaction products, (ii) calculations of the overall rate constant and branching ratios to different products using transition state and master equation methods, and (iii) an experimental determination of the H atom yield from the reaction. The ab initio calculations show that reaction occurs predominantly via the initial formation of a datively bound HC-NH(3) complex and reveal low energy pathways to three sets of reaction products: H(2)CNH + H, HCNH(2) + H, and CH(3) + NH. The transition state calculations indicate the roles of "outer" and "inner" transition states and yield rate constants between 20 and 320 K that are in moderate agreement with the experimental values. These calculations and those using the master equation approach show that the branching ratio for the most exothermic reaction, to H(2)CNH + H, is ca. 96% throughout the temperature range covered by the calculations, with those to HCNH(2) + H and CH(3) + NH being (4 ± 3)% and <0.3%, respectively. In the experiments, multiple photon dissociation of CHBr(3) was used to generate CH radicals and laser-induced fluorescence at 121.56 nm (VUV-LIF) was employed to observe H atoms. By comparing signals from CH + NH(3) with those from CH + CH(4), where the yield of H atoms is known to be unity, it is possible to estimate that the yield of H atoms from CH + NH(3) is equal to 0.89 ± 0.07 (2σ), in satisfactory agreement with the theoretical estimate.

  3. Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Kim, Hye Yun; Kim, Hyunjin V; Yoon, Jin H; Kang, Bo Ram; Cho, Soo Min; Lee, Sejin; Kim, Ji Yoon; Kim, Joo Won; Cho, Yakdol; Woo, Jiwan; Kim, YoungSoo

    2014-12-12

    Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.

  4. Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice.

    Science.gov (United States)

    Lovell, Mark A; Xiong, Shuling; Lyubartseva, Ganna; Markesbery, William R

    2009-06-01

    To evaluate potential antioxidant characteristics of organic selenium (Se), double knock-in transgenic mice expressing human mutations in the amyloid precursor protein (APP) and human presenilin-1 (PS1) were provided a Se-deficient diet, a Se-enriched diet (Sel-Plex), or a control diet from 4 to 9 months of age followed by a control diet until 12 months of age. Levels of DNA, RNA, and protein oxidation as well as lipid peroxidation markers were determined in all mice and amyloid beta-peptide (Abeta) plaques were quantified. APP/PS1 mice provided Sel-Plex showed significantly (PSel-Plex-treated mice showed no significant differences in levels of lipid peroxidation or protein oxidation compared to APP/PS1 mice on a control diet. To determine if diminished oxidative damage was associated with increased antioxidant enzyme activities, brain glutathione peroxidase (GSH-Px), glutathione reductase, and glutathione transferase activities were measured. Sel-Plex-treated mice showed a modest but significant increase in GSH-Px activity compared to mice on a normal diet (P<0.5). Overall, these data suggest that organic Se can reduce Abeta burden and minimize DNA and RNA oxidation and support a role for it as a potential therapeutic agent in neurologic disorders with increased oxidative stress.

  5. Allicin ameliorates cognitive impairment in APP/PS1 mice via Suppressing oxidative stress by Blocking JNK Signaling Pathways.

    Science.gov (United States)

    Zhang, Hao; Wang, Ping; Xue, Yixue; Liu, Libo; Li, Zhen; Liu, Yunhui

    2018-02-01

    In middle and old age, Alzheimer's disease (AD) is a progressive neurodegenerative disorder of brain. As an increasingly aging population, AD represents a huge burden for the patients' family and the country. However, current therapeutical strategies have shown limited effectiveness. Allicin, which is the main composition of garlic, was reported to prevent the learning and memory impairment of AD mouse model. As the mechanism is not clear, in this study, we used the APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice, which express human mutant APP and PS1, to determine the protective effect of allicin on neurons. AD involves a broad range of clinical, cellular, and biochemical manifestations. This has led to many views of AD, e.g. the amyloid, presenilin, oxidative stress, and mitochondrial dysfunction. We confirmed that allicin improves the cognitive function of APP/PS1 double transgenic mice by reducing the expression levels of Aβ, oxidative stress, and improving mitochondrial dysfunction. Application of behavioral, morphological and molecular biology, and other means were conducted to investigate the effect of allicin, which provide an experimental basis for the reliable application of allicin in the treatment of neurodegenerative diseases. Copyright © 2017. Published by Elsevier Ltd.

  6. Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice

    Directory of Open Access Journals (Sweden)

    Moon Gyeong

    2011-10-01

    Full Text Available Abstract Background Evidence suggests that rheumatoid arthritis (RA may enhance or reduce the progression of Alzheimer's disease (AD. The present study was performed to directly explore the effects of collagen-induced rheumatoid arthritis (CIA on amyloid plaque formation, microglial activation, and microvascular pathology in the cortex and hippocampus of the double transgenic APP/PS1 mouse model for AD. Wild-type or APP/PS1 mice that received type II collagen (CII in complete Freund's adjuvant (CFA at 2 months of age revealed characteristics of RA, such as joint swelling, synovitis, and cartilage and bone degradation 4 months later. Joint pathology was accompanied by sustained induction of IL-1β and TNF-α in plasma over 4 weeks after administration of CII in CFA. Results CIA reduced levels of soluble and insoluble amyloid beta (Aβ peptides and amyloid plaque formation in the cortex and hippocampus of APP/PS1 mice, which correlated with increased blood brain barrier disruption, Iba-1-positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced vessel density and length with features of microvascular pathology, including vascular segments, thinner vessels, and atrophic string vessels. Conclusions The present findings suggest that RA may exert beneficial effects against Aβ burden and harmful effects on microvascular pathology in AD.

  7. Tongluo Xingnao Effervescent Tablet preserves mitochondrial energy metabolism and attenuates cognition deficits in APPswe/PS1De9 mice.

    Science.gov (United States)

    Dai, Yuan; Ma, Tao; Ren, Xiangyi; Wei, Jiangping; Fu, Wenjun; Ma, Yuntong; Xu, Shijun; Zhang, Zhanjun

    2016-09-06

    Tongluo Xingnao Effervescent Tablet (TXET), a traditional Chinese herbal formula composed of Ligusticum chuanxiong hor, Scutellaria baicalensis Georgi and Angelica sinensis, has been widely used to treat Alzheimer's disease (AD) and related dementias for decades in China. In the present study, we investigated the effects of TXET on mitochondrial function, energy metabolism and cognitive amelioration in the APPswe/PS1De9 transgenetic mouse model of AD. The energy charge and phosphocreatine, activity of the mitochondrial electron transport chain complexes, mitochondrial membrane potential, activity of Na(+)-K(+) ATPase and the expression levels of Bcl-2 and Bax in the brains were measured, respectively. TXET exhibits significant protection on mitochondrial function and energy supply in addition to ameliorating cognitive decline in APPswe/PS1De9 mice. TXET rescues mitochondrial function by increasing the mitochondrial membrane potential, energy charge levels, activity of respiratory chain complexes and Na(+)-K(+) ATPase activity. These findings suggest that TXET may attenuate cognition impairment through the restoration of mitochondrial function and energy metabolism in the brains in APPswe/PS1De9 mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Atmospheric reaction of Cl + methacrolein: a theoretical study on the mechanism, and pressure- and temperature-dependent rate constants.

    Science.gov (United States)

    Sun, Cuihong; Xu, Baoen; Zhang, Shaowen

    2014-05-22

    Methacrolein is a major degradation product of isoprene, the reaction of methacrolein with Cl atoms may play some roles in the degradation of isoprene where these species are relatively abundant. However, the energetics and kinetics of this reaction, which govern the reaction branching, are still not well understood so far. In the present study, two-dimensional potential energy surfaces were constructed to analyze the minimum energy path of the barrierless addition process between Cl and the C═C double bond of methacrolein, which reveals that the terminal addition intermediate is directly formed from the addition reaction. The terminal addition intermediate can further yield different products among which the reaction paths abstracting the aldehyde hydrogen atom and the methyl hydrogen atom are dominant reaction exits. The minimum reaction path for the direct aldehydic hydrogen atom abstraction is also obtained. The reaction kinetics was calculated by the variational transition state theory in conjunction with the master equation method. From the theoretical model we predicted that the overall rate constant of the Cl + methacrolein reaction at 297 K and atmospheric pressure is koverall = 2.3× 10(-10) cm(3) molecule(-1) s(-1), and the branching ratio of the aldehydic hydrogen abstraction is about 12%. The reaction is pressure dependent at P < 10 Torr with the high pressure limit at about 100 Torr. The calculated results could well account for the experimental observations.

  9. A quasi-QSPR modelling for the photocatalytic decolourization rate constants and cellular viability (CV%) of nanoparticles by CORAL.

    Science.gov (United States)

    Toropova, A P; Toropov, A A; Benfenati, E

    2015-01-01

    Most quantitative structure-property/activity relationships (QSPRs/QSARs) predict various endpoints related to organic compounds. Gradually, the variety of organic compounds has been extended to inorganic, organometallic compounds and polymers. However, the so-called molecular descriptors cannot be defined for super-complex substances such as different nanomaterials and peptides, since there is no simple and clear representation of their molecular structure. Some possible ways to define approaches for a predictive model in the case of super-complex substances are discussed. The basic idea of the approach is to change the traditionally used paradigm 'the endpoint is a mathematical function of the molecular structure' with another paradigm 'the endpoint is a mathematical function of available eclectic information'. The eclectic data can be (i) conditions of a synthesis, (ii) technological attributes, (iii) size of nanoparticles, (iv) concentration, (v) attributes related to cell membranes, and so on. Two examples of quasi-QSPR/QSAR analyses are presented and discussed. These are (i) photocatalytic decolourization rate constants (DRC) (10(-5)/s) of different nanopowders; and (ii) the cellular viability under the effect of nano-SiO(2).

  10. Theoretical study on the rate constants for the C2H5 + HBr --> C2H6 + Br reaction.

    Science.gov (United States)

    Sheng, Li; Li, Ze-Sheng; Liu, Jing-Yao; Xiao, Jing-Fa; Sun, Chia-Chung

    2004-02-01

    The reaction C(2)H(5) + HBr --> C(2)H(6) + Br has been theoretically studied over the temperature range from 200 to 1400 K. The electronic structure information is calculated at the BHLYP/6-311+G(d,p) and QCISD/6-31+G(d) levels. With the aid of intrinsic reaction coordinate theory, the minimum energy paths (MEPs) are obtained at the both levels, and the energies along the MEP are further refined by performing the single-point calculations at the PMP4(SDTQ)/6-311+G(3df,2p)//BHLYP and QCISD(T)/6-311++G(2df,2pd)//QCISD levels. The calculated ICVT/SCT rate constants are in good agreement with available experimental values, and the calculate results further indicate that the C(2)H(5) + HBr reaction has negative temperature dependence at T 850 K. The current work predicts that the kinetic isotope effect for the title reaction is inverse in the temperature range from 200 to 482 K, i.e., k(HBr)/k(DBr) < 1. Copyright 2003 Wiley Periodicals, Inc.

  11. Using a Family of Dividing Surfaces Normal to the Minimum EnergyPath for Quantum Instanton Rate Constants

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yimin; Miller, Wlliam H.

    2006-02-22

    One of the outstanding issues in the quantum instanton (QI) theory (or any transition state-type theory) for thermal rate constants of chemical reactions is the choice of an appropriate ''dividing surface'' (DS) that separates reactants and products. (In the general version of the QI theory, there are actually two dividing surfaces involved.) This paper shows one simple and general way for choosing DS's for use in QI Theory, namely using the family of (hyper) planes normal to the minimum energy path (MEP) on the potential energy surface at various distances s along it. Here the reaction coordinate is not one of the dynamical coordinates of the system (which will in general be the Cartesian coordinates of the atoms), but rather simply a parameter which specifies the DS. It is also shown how this idea can be implemented for an N-atom system in 3d space in a way that preserves overall translational and rotational invariance. Numerical application to a simple system (the colliner H + H{sub 2} reaction) is presented to illustrate the procedure.

  12. Low-pressure effective fluorescence lifetimes and photo-physical rate constants of one- and two-ring aromatics

    Science.gov (United States)

    Benzler, Thorsten; Faust, Stephan; Dreier, Thomas; Schulz, Christof

    2015-12-01

    One- and two-ring aromatics such as toluene and naphthalene are frequently used molecular tracer species in laser-induced fluorescence (LIF) imaging diagnostics. Quantifying LIF signal intensities requires knowledge of the photo-physical processes that determine the fluorescence quantum yield. Collision-induced and intramolecular energy transfer processes in the excited electronic state closely interact under practical conditions. They can be separated through experiments at variable low pressures. Effective fluorescence lifetimes of gaseous toluene, 1,2,4-trimethylbenzene, anisole, naphthalene, and 1-methylnaphthalene diluted in CO2 were measured after picosecond laser excitation at 266 nm and time-resolved detection of fluorescence intensities. Measurements in an optically accessible externally heated cell between 296 and 475 K and 0.010-1 bar showed that effective fluorescence lifetimes generally decrease with temperature, while the influence of the bath-gas pressure depends on the respective target species and temperature. The results provide non-radiative and fluorescence rate constants and experimentally validate the effect of photo-induced cooling.

  13. SP-A binds alpha1-antitrypsin in vitro and reduces the association rate constant for neutrophil elastase

    Directory of Open Access Journals (Sweden)

    Carrabino Natalia

    2005-12-01

    Full Text Available Abstract Background α1-antitrypsin and surfactant protein-A (SP-A are major lung defense proteins. With the hypothesis that SP-A could bind α1-antitrypsin, we designed a series of in vitro experiments aimed at investigating the nature and consequences of such an interaction. Methods and results At an α1-antitrypsin:SP-A molar ratio of 1:1, the interaction resulted in a calcium-dependent decrease of 84.6% in the association rate constant of α1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of α1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing α1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the α1-antitrypsin amino acid backbone and interaction between carbohydrates of both proteins are also possible. Gel filtration chromatography and turnover per inactivation experiments indicated that one part of SP-A binds several molar parts of α1-antitrypsin. Conclusion We conclude that the binding of SP-A to α1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of α1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.

  14. Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both Aβ and Tau pathologies.

    Science.gov (United States)

    Li, Cong; Guo, Xiao-Dan; Lei, Min; Wu, Jia-Yi; Jin, Jia-Zhen; Shi, Xiao-Fan; Zhu, Zhi-Yuan; Rukachaisirikul, Vatcharin; Hu, Li-Hong; Wen, Tie-Qiao; Shen, Xu

    2017-01-01

    Considering the complicated pathogenesis of Alzheimer's disease (AD), multi-targets have become a focus in the discovery of drugs for treatment of this disease. In the current work, we established a multi-target strategy for discovering active reagents capable of suppressing both Aβ level and Tau hyperphosphorylation from natural products, and found that the ethanol extract of Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1 transgenic mice by inhibiting both Aβ levels and Tau hyperphosphorylation. SH-SY5Y and CHO-APP/BACE1 cells and primary astrocytes were used in cell-based assays. APP/PS1 transgenic mice [B6C3-Tg(APP swe , PS1dE9)] were administered THA (300 mg·kg -1 ·d -1 , ig) for 100 d. After the administration was completed, the learning ability of the mice was detected using a Morris water maze (MWM) assay; immunofluorescence staining, Congo red staining and Thioflavine S staining were used to detect the senile plaques in the brains of the mice. ELISA was used to evaluate Aβ and sAPPβ contents, and Western blotting and RT-PCR were used to investigate the relevant signaling pathway regulation in response to THA treatment. In SH-SY5Y cells, THΑ (1, 10, 20 μg/mL) significantly stimulated PI 3 K/AKT/mTOR and AMPK/raptor/mTOR signaling-mediated autophagy in the promotion of Aβ clearance as both a PI 3 K inhibitor and an AMPK indirect activator, and restrained Aβ production as a suppressor against PERK/eIF2α-mediated BACE1 expression. Additionally, THA functioned as a GSK3β inhibitor with an IC 50 of 1.32±0.85 μg/mL, repressing Tau hyperphosphorylation. Similar effects on Aβ accumulation and Tau hyperphosphorylation were observed in APP/PS1 transgenic mice treated with THA. Furthermore, administration of THA effectively improved the learning ability of APP/PS1 transgenic mice, and markedly reduced the number of senile plaques in their hippocampus and cortex. The results highlight the potential of the natural product THA

  15. Rate constants of nine C6-C9 alkanes with OH from 230 to 379 K: chemical tracers for [OH].

    Science.gov (United States)

    Sprengnether, Michele M; Demerjian, Kenneth L; Dransfield, Timothy J; Clarke, James S; Anderson, James G; Donahue, Neil M

    2009-04-30

    We report absolute rate-constant measurements for the reactions of nine C(6)-C(9) alkanes with OH in 8-10 torr of nitrogen from 230 to 379 K in the Harvard University High-Pressure Flow System. Hydroxyl concentrations were measured using laser-induced fluorescence, and alkane concentrations were measured using Fourier transform infrared Spectroscopy. Ethane's reactivity was simultaneously measured as a test of experimental performance. Results were fit to a modified Arrhenius equation based on transition state theory (ignoring tunneling), k(T) = Be(-E(a)/T)/(T(1 - e(- 1.44nu(1)/T))(2)(1 - e(- 1.44nu(2)/T)), with nu(1) and nu(2) bending frequencies, set to 280 and 500 cm(-1). Results were as follows for B (10(-9) K cm(3) s(-1)), E(a) (K), and k(298) (10(-12) cm(3) s(-1)): cyclohexane, 3.24 +/- 0.14, 332 +/- 12, 7.13; cyclo-octane, 3.47 +/- 0.30, 149 +/- 26, 14.1; 2-methylhexane, 1.45 +/- 0.08, 110 +/- 15, 6.72; 3-methylhexane, 1.50 +/- 0.08, 128 +/- 16, 6.54; methylcyclopentane, 1.65 +/- 0.07, 109 +/- 13, 7.65; methylcyclohexane, 1.86 +/- 0.09, 83 +/- 14, 9.43; methylcycloheptane, 3.45 +/- 0.45, 142 +/- 36, 14.4; n-propylcyclohexane, 2.83 +/- 0.14, 112 +/- 15, 13.0; isopropylcyclohexane, 1.79 +/- 0.11, -44 +/- 34, 13.9. Uncertainties are one sigma results from linear regression fits and are likely underestimated. Room temperature rate coefficients of reaction are accurate to within 10% at two sigma. A comprehensive fit to 17 separate studies including the present work for cyclohexane gives good agreement with the present results: terms as above, 3.09 +/- 0.12, 326 +/- 12, 6.96. Five of these compounds are routinely measured in urban air within a suite of atmospheric nonmethane hydrocarbons and reach parts per billion levels. The remaining four are C8-C9 cycloalkanes with low anthropogenic emissions. Because of their high, specific reactivity with OH, their concentration decays may be used as an indirect measurement of [OH] in the atmosphere or laboratory. This data

  16. Sensitivity of ozone concentrations to rate constants in a modified SAPRC90 chemical mechanism used for Canadian lower Fraser Valley ozone studies

    Science.gov (United States)

    Jiang, Weimin; Singleton, Donald L.; Mclaren, Robert; Hedley, Mark

    The SAPRC90 chemical mechanism implemented in CALGRID is modified and updated for the specific emissions and applications of the Lower Fraser Valley (LFV) of British Columbia, Canada. Explicit reactions related to biogenic emissions and alternative fuels are added. The sensitivity of ozone formation to rate parameters in the mechanism is determined for an episode specific trajectory which originates under relatively clean marine conditions and passes over the urban core of Vancouver during the morning rush hour. Of the 137 reactions in the modified mechanism, the rate constants of 44 reactions are found to have a high sensitivity on ozone formation. The 44 reactions are further divided into general sensitive reactions, for which rate constant changes near the base case values have observable effects on maximum ozone concentrations, and limit-sensitive reactions, for which rate constant changes of more than an order of magnitude are required to have an observable impact on ozone concentrations. For the sensitive reactions, both ozone sensitivity coefficients for small changes (20%) in the rate constants and effects on ozone caused by large rate constant changes (factors of 0, 0.5, and 2) are calculated. Of note is the importance of several photolysis reactions and the reactions of OH with a class of reactive aromatics, including xylenes, on ozone concentrations in the LFV.

  17. Interaction of rare gas metastable atoms. [Differential and total cross sections, elastic scattering, ionization, potential scattering, phase shifts, rate constants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, A.Z.F.

    1977-11-01

    The physical and chemical properties of metastable rare gas atoms are discussed and summarized. This is followed by a detailed examination of the various possible pathways whereby the metastable's excess electronic energy can be dissipated. The phenomenon of chemi-ionization is given special emphasis, and a theoretical treatment based on the use of complex (optical) potential is presented. This is followed by a discussion on the unique advantages offered by elastic differential cross section measurements in the apprehension of the fundamental forces governing the ionization process. The methodology generally adopted to extract information about the interaction potential for scattering data is also systematically outlined. Two widely studied chemi-ionization systems are then closely examined in the light of accurate differential cross section measurements obtained in this work. The first system is He(2/sup 3/S) + Ar for which one can obtain an interaction potential which is in good harmony with the experimental results of other investigators. The validity of using the first-order semiclassical approximation for the phase shifts calculation in the presence of significant opacities is also discussed. The second reaction studied is He*+D/sub 2/ for which measurements were made on both spin states of the metastable helium. A self-consistent interaction potential is obtained for the triplet system, and reasons are given for not being able to do likewise for the singlet system. The anomalous hump proposed by a number of laboratories is analyzed. Total elastic and ionization cross sections as well as rate constants are calculated for the triplet case. Good agreement with experimental data is found. Finally, the construction and operation of a high power repetitively pulsed nitrogen laser pumped dye laser system is described in great details. Details for the construction and operation of a flashlamp pumped dye laser are likewise given.

  18. Titration of the plasma effect site equilibrium rate constant of propofol; a link method of 'Concentration-Probability-Time'.

    Science.gov (United States)

    Kim, Jong-Yeop; Park, Sung-Yong; Park, Sun-Kyung; Kim, Jin-Soo; Min, Sang-Kee

    2010-03-01

    The plasma effect-site equilibrium rate constant (k(e0)) of propofol has been reported in various pharmacodynamic studies; however, it is not desirable to apply k(e0) for the link with pharmacokinetic models that were separately investigated. Thus, we titrated k(e0) for the pharmacokinetic model, which is known as the multiple covariates adjusted model of propofol. Ninety female patients scheduled for gynecologic surgery were randomly assigned to three groups targeting different plasma concentrations of 5.4, 8.1, and 10.8 microg/ml. Target-controlled infusions (TCI) were provided by a computer-assisted continuous infusion system. Time to loss of responsiveness (LOR) was measured by a blind investigator; effect-site concentrations (C(e)) for LOR were then calculated with simulation of TCI using different k(e0)s. We determined the k(e0) minimizing total discrepancy (TD) between the inputted and calculated k(e0) from the t(1/2)k(e0)s for a given probability of LOR of the C(e), and also obtained the k(e0) for the minimal TD between the median C(e), which were compared to the known k(e0). K(e0)s from these two methods were 0.3692 and 0.3788/min. C(e)s for LOR with these k(e0)s were significantly different from those with Schnider's k(e0). We proposed a method for titration of the k(e0) of propofol. The k(e0)s of propofol was lower than Schnider's k(e0). An adequate k(e0) for the specific pharmacokinetic model and a certain population would be useful for prediction of an accurate C(e), and could be used for calculation of accurate dosing during targeting of the effect site.

  19. Donepezil improves learning and memory deficits in APP/PS1 mice by inhibition of microglial activation.

    Science.gov (United States)

    Guo, H B; Cheng, Y F; Wu, J G; Wang, C M; Wang, H T; Zhang, C; Qiu, Z K; Xu, J P

    2015-04-02

    Donepezil, a cholinesterase inhibitor, is a representative symptomatic therapy for Alzheimer's disease (AD). Recent studies have reported the anti-inflammatory effects of donepezil. However, limited studies that investigate its anti-inflammatory effect in AD have been reported. Considering the role of proinflammatory molecules and microglial activation in the pathogenesis of AD, the current study aimed to elucidate the effects of donepezil on microglial activation induced by amyloid deposition in transgenic mice. Our results showed that chronic treatment with donepezil significantly improved the cognitive function in the novel object recognition test and Morris water maze test in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. We further demonstrated that these cognitive enhancements were related to the anti-inflammatory effect of donepezil. We found that donepezil could inhibit the expression of CD68, a specific marker of microglial activation, and reduce the release of proinflammatory cytokines including tumor necrosis factor-α and interleukin-1β. Immunohistochemistry and Congo red co-staining revealed that congophilic amyloid and activated microglia around plaques were also reduced by donepezil treatment. Enzyme-linked immunosorbent assay (ELISA) analysis showed that donepezil decreased insoluble Aβ40/Aβ42 and soluble Aβ40 levels. Moreover, donepezil reversed the impaired expression of insulin-degrading enzyme in the hippocampus of APP/PS1 mice. Our findings indicated that donepezil improves cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of microglial activation and release of proinflammatory cytokines. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Selective loss of noradrenaline exacerbates early cognitive dysfunction and synaptic deficits in APP/PS1 mice

    Science.gov (United States)

    Hammerschmidt, Thea; Kummer, Markus P.; Terwel, Dick; Martinez, Ana; Gorji, Ali; Pape, Hans-Christian; Rommelfanger, Karen S.; Schroeder, Jason P.; Stoll, Monika; Schultze, Joachim; Weinshenker, David; Heneka, Michael T.

    2016-01-01

    Background Degeneration of the locus ceruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimer’s disease. Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect Aβ toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood. Methods To determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine β-hydroxylase (DBH) knock-out mice with APP/PS1 mice, overexpressing mutant amyloid precursor protein and presenilin-1. DBH (−/−) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation (LTP), and synaptic protein levels were assessed. Results The modest impairments in spatial memory and hippocampal LTP displayed by young APP/PS1 or DBH(−/−) single mutant mice were augmented in DBH(−/−)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of total Ca2+/calmodulin-dependent protein kinases II (CaMKII) and N-Methyl-D-aspartate receptor 2A (NR2A), increased N-Methyl-D-aspartate receptor 2B (NR2B) levels and were independent of Aβ accumulation. Spatial memory performance was partly improved by treatment with the NA precursor drug L-threo-DOPS. Conclusions These results indicate that early LC degeneration and subsequent NA deficiency in AD may contribute to cognitive deficits via altered levels of CaMKII and N-Methyl-D-aspartate receptors, and suggest that NA supplementation could be beneficial in early AD. PMID:22883210

  1. Determination of equilibrium and rate constants for complex formation by fluorescence correlation spectroscopy supplemented by dynamic light scattering and Taylor dispersion analysis.

    Science.gov (United States)

    Zhang, Xuzhu; Poniewierski, Andrzej; Jelińska, Aldona; Zagożdżon, Anna; Wisniewska, Agnieszka; Hou, Sen; Hołyst, Robert

    2016-10-04

    The equilibrium and rate constants of molecular complex formation are of great interest both in the field of chemistry and biology. Here, we use fluorescence correlation spectroscopy (FCS), supplemented by dynamic light scattering (DLS) and Taylor dispersion analysis (TDA), to study the complex formation in model systems of dye-micelle interactions. In our case, dyes rhodamine 110 and ATTO-488 interact with three differently charged surfactant micelles: octaethylene glycol monododecyl ether C12E8 (neutral), cetyltrimethylammonium chloride CTAC (positive) and sodium dodecyl sulfate SDS (negative). To determine the rate constants for the dye-micelle complex formation we fit the experimental data obtained by FCS with a new form of the autocorrelation function, derived in the accompanying paper. Our results show that the association rate constants for the model systems are roughly two orders of magnitude smaller than those in the case of the diffusion-controlled limit. Because the complex stability is determined by the dissociation rate constant, a two-step reaction mechanism, including the diffusion-controlled and reaction-controlled rates, is used to explain the dye-micelle interaction. In the limit of fast reaction, we apply FCS to determine the equilibrium constant from the effective diffusion coefficient of the fluorescent components. Depending on the value of the equilibrium constant, we distinguish three types of interaction in the studied systems: weak, intermediate and strong. The values of the equilibrium constant obtained from the FCS and TDA experiments are very close to each other, which supports the theoretical model used to interpret the FCS data.

  2. DHA diet reduces AD pathology in young APPswe/PS1ΔE9 transgenic mice: Possible Gender Effects

    OpenAIRE

    Perez, Sylvia E.; Berg, Brian M.; Moore, Kenneth A.; He, Bin; Counts, Scott E.; Fritz, Jason J.; Hu, Yuan-Shih; Lazarov, Orly; Lah, James J.; Mufson, Elliott J.

    2010-01-01

    Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzhemier’s disease (AD). We examined the effects of short-term (3 months) DHA enriched diet on plaque deposition and synaptic deficts in forebrain of young APPswe/PS1ΔE9 transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg...

  3. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan J; Metaxas, Athanasios; Ibáñez-Vea, María

    2016-01-01

    -linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth......, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all...

  4. Deletion of the type-1 interferon receptor in APPSWE/PS1ΔE9 mice preserves cognitive function and alters glial phenotype.

    Science.gov (United States)

    Minter, Myles R; Moore, Zachery; Zhang, Moses; Brody, Kate M; Jones, Nigel C; Shultz, Sandy R; Taylor, Juliet M; Crack, Peter J

    2016-07-11

    A neuro-inflammatory response is evident in Alzheimer's disease (AD), yet the precise mechanisms by which neuro-inflammation influences the progression of Alzheimer's disease (AD) remain poorly understood. Type-1 interferons (IFNs) are master regulators of innate immunity and have been implicated in multiple CNS disorders, however their role in AD progression has not yet been fully investigated. Hence, we generated APPSWE/PS1ΔE9 mice lacking the type-1 IFN alpha receptor-1 (IFNAR1, APPSWE/PS1ΔE9 x IFNAR1(-/-)) aged to 9 months to investigate the role of type-1 IFN signaling in a well-validated model of AD. APPSWE/PS1ΔE9 x IFNAR1(-/-) mice displayed a modest reduction in Aβ monomer levels, despite maintenance of plaque deposition. This finding correlated with partial rescue of spatial learning and memory impairments in the Morris water maze in comparison to APPSWE/PS1ΔE9 mice. Q-PCR identified a reduced type-1 IFN response and modulated pro-inflammatory cytokine secretion in APPSWE/PS1ΔE9 x IFNAR1(-/-) mice compared to APPSWE/PS1ΔE9 mice. Interestingly, immunohistochemistry displayed enhanced astrocyte reactivity but attenuated microgliosis surrounding amyloid plaque deposits in APPSWE/PS1ΔE9 x IFNAR1(-/-) mice in comparison to APPSWE/PS1ΔE9 mice. These APPSWE/PS1ΔE9 x IFNAR1(-/-) microglial populations demonstrated an anti-inflammatory phenotype that was confirmed in vitro by soluble Aβ1-42 treatment of IFNAR1(-/-) primary glial cultures. Our findings suggest that modulating neuro-inflammatory responses by suppressing type-1 IFN signaling may provide therapeutic benefit in AD.

  5. Quantum state-to-state rate constants for the rotationally inelastic collision of CH(B2Sigma(-), nu=0, N-->N') with Ar.

    Science.gov (United States)

    Chao, Sheng Der; Lin, Sheng Hsien; Alexander, Millard H

    2005-11-15

    We have calculated the state-to-state integral cross sections and rate constants for the rotationally inelastic collision of CH(B (2)Sigma(-), nu=0, N-->N') with Ar using the quantum coupled-state and close-coupling methods on an ab initio potential-energy surface constructed by Alexander et al. [J. Chem. Phys. 101, 4547 (1994)]. Overall the calculated rate constants are in good agreements with the three available experimental results. The rate constants are comparable to the usual gas kinetic and decrease with increasing N and DeltaN. For the multiquantum transition cases, the theory underestimates the experiment. We discuss some possible causes to the discrepancies among the theory and the experiments.

  6. Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses.

    Science.gov (United States)

    Marly, Charlotte; Bettschart-Wolfensberger, Regula; Nussbaumer, Paeivi; Moine, Sebastien; Ringer, Simone K

    2014-09-01

    To compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses. Prospective 'blinded' controlled trial using block randomization. Forty healthy Freiberger stallions. The horses received either intravenous (IV) romifidine (loading dose: 80 μg kg(-1) ; infusion: 30 μg kg(-1)  hour(-1) ) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 μg kg(-1) ; infusion: 29 μg kg(-1)  hour(-1) , and butorphanol loading: 18 μg kg(-1) ; infusion: 25 μg kg(-1)  hour(-1) ) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 μg kg(-1) ) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant. Sedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9-9.0 cm, RB: 8.8, 4.7-10.0 cm, and by the dentist R: 6.6, 3.0-8.2 cm, RB: 7.9, 6.6-8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation. The described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous. © 2014 Association of Veterinary Anaesthetists and the

  7. Comparison of bolus injection and constant infusion methods for measuring muscle protein fractional synthesis rate in humans.

    Science.gov (United States)

    Tuvdendorj, Demidmaa; Chinkes, David L; Bahadorani, John; Zhang, Xiao-jun; Sheffield-Moore, Melinda; Killewich, Lois A; Wolfe, Robert R

    2014-12-01

    The use of stable isotope tracer techniques to measure muscle protein fractional synthesis rate (FSR) has been well established and widely used. The most common method that has been utilized so far is a primed constant infusion (CI) method, which requires 3-4 h of tracer infusion. However, recently our group has developed a bolus injection (BI) method, which requires an injection of bolus of tracer and can be completed within 1 h. In this study, we compared calf (gastrocnemius) muscle protein FSR measured using these two different methods--CI and BI. FSRs were measured in eight people (5 men and 3 women; age: 62.3±6.9 years (mean±SD); body weight: 75.4±21.5 kg) at basal, postabsorptive state using L-[ring-2H5]-phenylalanine. In the CI protocol, a primed continuous infusion was given for 4 h, and muscle biopsies were taken at 120 and 240 min; in the BI, a bolus injection of the tracer was given at 0 min and biopsies were taken at 5 and 60 min. Tracer enrichments in blood and muscle tissue were determined by gas chromatography-mass spectrometry. Data are expressed as mean±SE; t-test, linear regression and Levene Median equal variance test analyses were performed. CI FSR was 0.066±0.006%/h, whereas BI FSR was 0.058±0.008%/h, p=NS. The linear regression analysis showed a significant relationship between BI and CI, p=0.038. The intra-class correlation coefficient was 0.83. The standard deviation of the differences in the measurements was 0.015%/h. The Levene Median equal variance test demonstrated no difference in variance between the CI and BI measurements (p=0.722). No difference could be detected in calf muscle protein FSR measured by CI and BI methods; the BI method can be used for the measurement of muscle protein FSR in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. APP substitutions V715F and L720P alter PS1 conformation and differentially affect Abeta and AICD generation.

    Science.gov (United States)

    Tesco, Giuseppina; Ginestroni, Andrea; Hiltunen, Mikko; Kim, Minji; Dolios, Georgia; Hyman, Bradley T; Wang, Rong; Berezovska, Oksana; Tanzi, Rudolph E

    2005-10-01

    The 37-43 amino acid Abeta peptide is the principal component of beta-amyloid deposits in Alzheimer's disease (AD) brain, and is derived by serial proteolysis of the amyloid precursor protein (APP) by beta- and gamma-secretase. gamma-Secretase also cleaves APP at Val50 in the Abeta numbering (epsilon cleavage), resulting in the release of a fragment called APP intracellular domain (AICD). The aim of this study was to determine whether amino acid substitutions in the APP transmembrane domain differentially affect Abeta and AICD generation. We found that the APPV715F substitution, which has been previously shown to dramatically decrease Abeta40 and Abeta42 while increasing Abeta38 levels, does not affect in vitro generation of AICD. Furthermore, we found that the APPL720P substitution, which has been previously shown to prevent in vitro generation of AICD, completely prevents Abeta generation. Using a fluorescence resonance energy transfer (FRET) method, we next found that both the APPV715F and APPL720P substitutions significantly increase the distance between the N- and C-terminus of presenilin 1 (PS1), which has been proposed to contain the catalytic site of gamma-secretase. In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on Abeta and AICD production.

  9. VizieR Online Data Catalog: Candidate rotating M dwarfs from PS1-MDS (Kado-Fong+, 2016)

    Science.gov (United States)

    Kado-Fong, E.; Williams, P. K. G.; Mann, A. W.; Berger, E.; Burgett, W. S.; Chambers, K. C.; Huber, M. E.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Rest, A.; Wainscoat, R. J.; Waters, C.

    2017-05-01

    The Pan-STARRS1 Medium-Deep Survey (PS1-MDS) was performed on the 1.8m Pan-STARRS1 telescope situated on Mount Haleakala, Hawai'i, equipped with five broadband filters, (grizy)P1. The PS1 filters are similar to those used in the Sloan Digital Sky Survey (SDSS), but include a yP1 filter (λeff~9600Å), a bluer cutoff in the z band (Δλ~1000Å rather than 1400Å), a 200Å redder cutoff in the g band, and no u band. We identified candidate cool dwarfs using color cuts as described in section 2.4. We searched for periodic variations in the light curves of our candidate cool stars using the multiband extension of the Lomb-Scargle periodogram introduced by VanderPlas & Ivezic (2015ApJ...812...18V); see section 3. We list the confirmed rotators in Table 3. (2 data files).

  10. Mutations in AtPS1 (Arabidopsis thaliana parallel spindle 1 lead to the production of diploid pollen grains.

    Directory of Open Access Journals (Sweden)

    Isabelle d'Erfurth

    2008-11-01

    Full Text Available Polyploidy has had a considerable impact on the evolution of many eukaryotes, especially angiosperms. Indeed, most--if not all-angiosperms have experienced at least one round of polyploidy during the course of their evolution, and many important crop plants are current polyploids. The occurrence of 2n gametes (diplogametes in diploid populations is widely recognised as the major source of polyploid formation. However, limited information is available on the genetic control of diplogamete production. Here, we describe the isolation and characterisation of the first gene, AtPS1 (Arabidopsis thaliana Parallel Spindle 1, implicated in the formation of a high frequency of diplogametes in plants. Atps1 mutants produce diploid male spores, diploid pollen grains, and spontaneous triploid plants in the next generation. Female meiosis is not affected in the mutant. We demonstrated that abnormal spindle orientation at male meiosis II leads to diplogamete formation. Most of the parent's heterozygosity is therefore conserved in the Atps1 diploid gametes, which is a key issue for plant breeding. The AtPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. The isolation of a gene involved in diplogamete production opens the way for new strategies in plant breeding programmes and progress in evolutionary studies.

  11. PS1-17: Assessing Communication During Cancer Care: Multiple Perspectives, Multiple Considerations

    Science.gov (United States)

    Gaglio, Bridget; Arora, Neeraj; Boggs, Jennifer; Lemay, Celeste; Firneno, Cassandra; Mazor, Kathleen

    2012-01-01

    Background/Aims Patient-centered communication (PCC) between clinicians and patients is necessary for quality care. Measurement of communication over the cancer care continuum is an important step in describing current practices and remediating breakdowns. As a first step in developing a system to assess PCC longitudinally across the cancer care continuum, we interviewed patients, family members, physicians, health information technology (HIT) leaders, and health plan leaders. The purpose of the present study was to expand our understanding of possible approaches to create and implement such a system by conducting a symposium with experts and stakeholders. Methods We conducted a symposium with experts in the field of HIT, academic researchers, investigators from the 14 Cancer Research Network sites, information technology (IT) advisors from each CRN site, National Cancer Institute staff, and investigators and consultants involved with the project. The purpose of the symposium was to have experts in the field of HIT present possible approaches to computerizing data collection and feedback of patients’ experiences with PCC and to engage in an active dialogue around the strengths and weaknesses of the different approaches proposed. Prior to the meeting, we distributed a list of questions for the IT experts to address in their presentations, based on issues, which have been identified during the interviews. The symposium was digitally recorded, professionally transcribed, and coded using grounded theory approaches. Results Themes identified during the symposium focused on contextual factors to be considered when creating a communication feedback system; data liquidity, using one system in multiple healthcare environments that are very diverse, and hat modality to use when there are a variety of preferences for communication and the technology is constantly evolving. The symposium also confirmed themes that emerged from the interviews; the system would need to be

  12. Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice.

    Science.gov (United States)

    Sadowski, Marcin; Pankiewicz, Joanna; Scholtzova, Henrieta; Ji, Yong; Quartermain, David; Jensen, Catrin H; Duff, Karen; Nixon, Ralph A; Gruen, Rand J; Wisniewski, Thomas

    2004-05-01

    In Alzheimer disease (AD) patients, early memory dysfunction is associated with glucose hypometabolism and neuronal loss in the hippocampus. Double transgenic (Tg) mice co-expressing the M146L presenilin 1 (PS1) and K670N/M671L, the double "Swedish" amyloid precursor protein (APP) mutations, are a model of AD amyloid-beta deposition (Abeta) that exhibits earlier and more profound impairments of working memory and learning than single APP mutant mice. In this study we compared performance on spatial memory tests, regional glucose metabolism, Abeta deposition, and neuronal loss in APP/PS1, PS1, and non-Tg (nTg) mice. At the age of 2 months no significant morphological and metabolic differences were detected between 3 studied genotypes. By 8 months, however, APP/PS1 mice developed selective impairment of spatial memory, which was significantly worse at 22 months and was accompanied by reduced glucose utilization in the hippocampus and a 35.8% dropout of neurons in the CA1 region. PS1 mice exhibited a similar degree of neuronal loss in CA1 but minimal memory deficit and no impairment of glucose utilization compared to nTg mice. Deficits in 22 month APP/PS1 mice were accompanied by a substantially elevated Abeta load, which rose from 2.5% +/- 0.4% at 8 months to 17.4% +/- 4.6%. These findings implicate Abeta or APP in the behavioral and metabolic impairments in APP/PS1 mice and the failure to compensate functionally for PS1-related hippocampal cell loss.

  13. GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations.

    Science.gov (United States)

    Tesco, G; Tanzi, R E

    2000-01-01

    We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta-catenin. Since PS1 has been suggested to be involved in beta-catenin stabilization, we further investigated whether GSK3 beta, responsible for beta-catenin phosphorylation and degradation, is part of the PS1/beta-catenin complex. In naïve H4 and CHO cells, PS1 co-immunoprecipitated with both endogenous beta-catenin and GSK3 beta. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta-catenin in naïve CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma-secretase activity, we also tested whether PS1 endoproteolysis is required for beta-catenin/GSK3 beta/PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta-catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and delta E10) or the presence of PS1-FAD mutations does not interfere with beta-catenin/GSK3 beta/PS1 complex formation.

  14. Estimating reaction rate constants from a two-step reaction: a comparison between two-way and three-way methods

    NARCIS (Netherlands)

    Bijlsma, S.; Smilde, A. K.

    2000-01-01

    In this paper, two different spectral datasets are used in order to estimate reaction rate constants using different algorithms. Dataset 1 consists of short-wavelength near-infrared (SW NIR) spectra taken in time of the two-step epoxidation of 2,5-di-tert-butyl-1,4-benzoquinone using tert-butyl

  15. Room-temperature and temperature-dependent QSRR modelling for predicting the nitrate radical reaction rate constants of organic chemicals using ensemble learning methods.

    Science.gov (United States)

    Gupta, S; Basant, N; Mohan, D; Singh, K P

    2016-07-01

    Experimental determinations of the rate constants of the reaction of NO3 with a large number of organic chemicals are tedious, and time and resource intensive; and the development of computational methods has widely been advocated. In this study, we have developed room-temperature (298 K) and temperature-dependent quantitative structure-reactivity relationship (QSRR) models based on the ensemble learning approaches (decision tree forest (DTF) and decision treeboost (DTB)) for predicting the rate constant of the reaction of NO3 radicals with diverse organic chemicals, under OECD guidelines. Predictive powers of the developed models were established in terms of statistical coefficients. In the test phase, the QSRR models yielded a correlation (r(2)) of >0.94 between experimental and predicted rate constants. The applicability domains of the constructed models were determined. An attempt has been made to provide the mechanistic interpretation of the selected features for QSRR development. The proposed QSRR models outperformed the previous reports, and the temperature-dependent models offered a much wider applicability domain. This is the first report presenting a temperature-dependent QSRR model for predicting the nitrate radical reaction rate constant at different temperatures. The proposed models can be useful tools in predicting the reactivities of chemicals towards NO3 radicals in the atmosphere, hence, their persistence and exposure risk assessment.

  16. Structure-activity relationship for the estimation of OH-oxidation rate constants of aliphatic organic compounds in the aqueous phase: alkanes, alcohols, organic acids and bases

    National Research Council Canada - National Science Library

    Monod, A; Doussin, J.F

    2008-01-01

    ...-initiated oxidation of organic compounds have been determined experimentally, but a robust estimation method would be of high benefit to a wide community. Different methods have been explored so far. One method consists of correlations between the rate constant and the Bond Dissociation Energy (BDE), based on the method developed by Evans and Polanyi ...

  17. PS1-29: Resources to Facilitate Multi-site Collaboration: the PRIMER Research Toolkit

    Science.gov (United States)

    Greene, Sarah; Thompson, Ella; Baldwin, Laura-Mae; Neale, Anne Victoria; Dolor, Rowena

    2010-01-01

    Background and Aims: The national research enterprise has typically functioned in a decentralized fashion, resulting in duplicative or undocumented processes, impeding not only the pace of research, but diffusion of established best practices. To remedy this, many long-standing networks have begun capturing and documenting proven strategies to streamline and standardize various aspects of the research process. The project, “Partnership-driven Resources to IMprove and Enhance Research” (PRIMER), was funded through the Clinical and Translational Science Awards (CTSA) initiative to leverage the collective expertise from two networks: the HMO Research Network and Practice Based Research Networks (PBRNs). Each network has a shared goal of propagating research resources and best practices. Methods: We created and distributed an online survey to 92 CTSA and PBRN representatives in March, 2009 to define critical needs and existing resources that could inform a resource repository. The survey identified barriers and benefits to forming research partnerships, and assessed the perceived utility of various tools that could accelerate the research process. The study team identified, reviewed and organized tools based on the typical research trajectory from design to dissemination. Results: Fifty-five of 92 invitees (59%) completed the survey. Respondents rated the ability to conduct community-relevant research through true academic-community partnerships as the top-rated benefit of multi-site research, followed by the opportunity to accelerate translation of research into practice. The top two perceived barriers to multi-site research were ‘funding opportunities are not adequate (e.g., too few, not enough to support true collaborations), and ‘lack of research infrastructure to support [all] partners (e.g., no IT support, IRB, dedicated research staff). Respondents’ ratings of the utility of various tools and templates was used to guide development of an online

  18. Numerical counting ratemeter with large time constant for very low count rates - operational results; Ictometre numerique a grande constante de temps pour tres faible taux de comptage - resultats d'exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, J. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The use of an analogue ictometer poses technical problems for measuring low count rates. These latter call for time constants of up to 1000 sec. The numerical technique is better adapted and makes it possible to increase the time constant to 1000 sec. or over. The equipment described consists of 6 numerical ictometers fitted in a 3 U 3 drawer. By means of a clock it is possible to vary the counting time from 1 second to 1000 seconds, using values at 5, 10, 50, 100 and 500 seconds. The corresponding values of the frequency are 500 c/sec, 100, 50 10. 5. 1 and 0.5 c/sec with a resolving power of 0.2 per cent. The result appears on an indicator panel (galvanometer) and is available in the form of an analogue voltage suitable for a 50 mV MECI recorder. (author) [French] En utilisant un ictometre analogique, la mesure des taux de comptages faibles pose des problemes techniques. Les faibles taux de comptage exigent des constantes de temps allant jusqu'a 1000 s. La technique numerique se montre mieux adaptee et permet d'augmenter la constante de temps a 1000 s ou plus. L'ensemble decrit comporte 6 ictometres numeriques loges dans un tiroir 3 U 3. Une horloge permet de varier le temps de comptage de 1 seconde a 1000 secondes, passant par 5, 10, 50, 100, 500 secondes. Les gammes de frequences correspondantes sont 500, 100, 50, 10, 5, 1, 0,5 c/s avec une resolution de 2 pour 1000. Le resultat est affiche par un indicateur de tableaux (galvanometre) et est disponible en tension analogique pour l'enregistrement sur MECI (50 mV). (auteur)

  19. Absolute rate constant and O(3P yield for the O(1D+N2O reaction in the temperature range 227 K to 719 K

    Directory of Open Access Journals (Sweden)

    S. A. Carl

    2008-10-01

    Full Text Available The absolute rate constant for the reaction that is the major source of stratospheric NOx, O(1D+N2O → products, has been determined in the temperature range 227 K to 719 K, and, in the temperature range 248 K to 600 K, the fraction of the reaction that yields O(3P. Both the rate constants and product yields were determined using a recently-developed chemiluminescence technique for monitoring O(1D that allows for higher precision determinations for both rate constants, and, particularly, O(3P yields, than do other methods. We found the rate constant, kR1, to be essentially independent of temperature between 400 K and 227 K, having a value of (1.37±0.11×10−10 cm3 s−1, and for temperatures greater than 450 K a marked decrease in rate constant was observed, with a rate constant of only (0.94±0.11×10−10 cm3 s−1 at 719 K. The rate constants determined over the 227 K–400 K range show very low scatter and are significantly greater, by 20% at room temperature and 15% at 227 K, than the current recommended values. The fraction of O(3P produced in this reaction was determined to be 0.002±0.002 at 250 K rising steadily to 0.010±0.004 at 600 K, thus the channel producing O(3P can be entirely neglected in atmospheric kinetic modeling calculations. A further result of this study is an expression of the relative quantum yields as a function of temperature for the chemiluminescence reactions (kCL1C2H + O(1D → CH(A + CO and (kCL2C2H + O(3P → CH(A + CO, both followed by CH(A → CH(X + hν, as kCL1(T/kCL2(T=(32.8T−3050/(6.29T+398.

  20. Fitting the elementary rate constants of the P-gp transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm.

    Directory of Open Access Journals (Sweden)

    Deep Agnani

    Full Text Available P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the

  1. Ratiometric analysis in hyperpolarized NMR (I): test of the two-site exchange model and the quantification of reaction rate constants.

    Science.gov (United States)

    Li, Lin Z; Kadlececk, Stephen; Xu, He N; Daye, Dania; Pullinger, Benjamin; Profka, Harrilla; Chodosh, Lewis; Rizi, Rahim

    2013-10-01

    Conventional methods for the analysis of in vivo hyperpolarized (13) C NMR data from the lactate dehydrogenase (LDH) reaction usually make assumptions on the stability of rate constants and/or the validity of the two-site exchange model. In this study, we developed a framework to test the validity of the assumption of stable reaction rate constants and the two-site exchange model in vivo via ratiometric fitting of the time courses of the signal ratio L(t)/P(t). Our analysis provided evidence that the LDH enzymatic kinetics observed by hyperpolarized NMR are in near-equilibrium and satisfy the two-site exchange model for only a specific time window. In addition, we quantified both the forward and reverse exchange rate constants of the LDH reaction for the transgenic and mouse xenograft models of breast cancer using the ratio fitting method developed, which includes only two modeling parameters and is less sensitive to the influence of instrument settings/protocols, such as flip angles, degree of polarization and tracer dosage. We further compared the ratio fitting method with a conventional two-site exchange modeling method, i.e. the differential equation fitting method, using both the experimental and simulated hyperpolarized NMR data. The ratio fitting method appeared to fit better than the differential equation fitting method for the reverse rate constant on the mouse tumor data, with less relative errors on average, whereas the differential equation fitting method also resulted in a negative reverse rate constant for one tumor. The simulation results indicated that the accuracy of both methods depends on the width of the transport function, noise level and rate constant ratio; one method may be more accurate than the other based on the experimental/biological conditions aforementioned. We were able to categorize our tumor models into specific conditions of the computer simulation and to estimate the errors of rate quantification. We also discussed possible

  2. Smoluchowski Equations for Agglomeration in Conditions of Variable Temperature and Pressure and a New Scaling of Rate Constants: Application to Nozzle-Beam Expansion.

    Science.gov (United States)

    Chaiken, J; Goodisman, J; Kornilov, O

    2015-07-09

    The Smoluchowski equations provide a rigorous and efficient means for including multiple kinetic pathways when modeling coalescence growth systems. Originally written for a constant temperature and volume system, the equations must be modified if temperature and pressure vary during the coalescence time. In this paper, the equations are generalized, and adaptations appropriate to the situation presented by supersonic nozzle beam expansions are described. Given rate constants for all the cluster-cluster reactions, solution of the Smoluchowski equations would yield the abundances of clusters of all sizes at all times. This is unlikely, but we show that if these rate constants scale with the sizes of the reacting partners, the asymptotic (large size and large time) form of the cluster size distribution can be predicted. Experimentally determined distributions for He fit the predicted asymptotic distribution very well. Deviations between predicted and observed distributions allow identification of special cluster sizes that is, magic numbers. Furthermore, fitting an observed distribution to the theoretical form yields the base agglomeration cross section, from which all cluster-cluster rate constants may be obtained by scaling. Comparing the base cross section to measures of size and reactivity gives information about the coalescence process.

  3. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice.

    Science.gov (United States)

    McClean, Paula L; Jalewa, Jaishree; Hölscher, Christian

    2015-10-15

    Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we have shown that the diabetes drug liraglutide is protective in middle aged and in old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties. When injecting liraglutide once-daily ip. in two months old mice for 8 months, the main hallmarks of AD were much reduced. Memory formation in object recognition and Morris water maze were normalised and synapse loss and the loss of synaptic plasticity was prevented. In addition, amyloid plaque load, including dense core congophilic plaques, was much reduced. Chronic inflammation (activated microglia) was also reduced in the cortex, and neurogenesis was enhanced in the dentate gyrus. The results demonstrate that liraglutide may protect from progressive neurodegeneration that develops in AD. The drug is currently in clinical trials in patients with AD. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Effects of ovariectomy on autophagy and senile plaques in the brain of adult APP/PS1 double transgenic mice

    Directory of Open Access Journals (Sweden)

    Ming-liang XU

    2015-04-01

    Full Text Available Objective To investigate the effect of ovarian estrogen on autophagy and senile plaques (SP in the brain of adult APP/PS1 double transgenic mice, and inquire into the mechanism of Alzheimer disease (AD neuropathogenesis due to estrogen deficiency. Methods APP/PS1 AD mice (3-month old were divided into ovariectomy group (OVX-AD and sham group (sham-AD. Two months after operation, transmission electron microscopy (TEM was employed to observe the morphological structures of the brains of AD model mice, and immunohistochemical staining was performed to examine the changes in SP and autophagy-related proteins LC3 and Beclin-1 in the brain of AD model mice. Results Immunohistochemical staining showed that the number of SP in the brain of OVX-AD mice incrcased significantly compared with that in sham-AD mice, and distribution of SP was observed more extensively, including the cortex and hippocampus. The autophagy related proteins LC3 and Beclin-1 positive neurons were decreased greatly in the OVX-AD mice brain compared with that of sham-AD mice. TEM revealed a larger number of swollen and dark neurons in hippocampus of OVX-AD mice, while more autophagosome was observed around the neuronal processes in OVX-AD mice brain compared with sham-AD mice. Conclusion Estrogen deficiency may lead to delayed maturation of autophagy, decrease the activity and weaken the function of autophagy, which in turn may result in aggravation of pathological features of AD. DOI: 10.11855/j.issn.0577-7402.2015.01.06

  5. Determination of rate constants and branching ratios for TCE degradation by zero-valent iron using a chain decay multispecies model.

    Science.gov (United States)

    Hwang, Hyoun-Tae; Jeen, Sung-Wook; Sudicky, Edward A; Illman, Walter A

    2015-01-01

    The applicability of a newly-developed chain-decay multispecies model (CMM) was validated by obtaining kinetic rate constants and branching ratios along the reaction pathways of trichloroethene (TCE) reduction by zero-valent iron (ZVI) from column experiments. Changes in rate constants and branching ratios for individual reactions for degradation products over time for two columns under different geochemical conditions were examined to provide ranges of those parameters expected over the long-term. As compared to the column receiving deionized water, the column receiving dissolved CaCO3 showed higher mean degradation rates for TCE and all of its degradation products. However, the column experienced faster reactivity loss toward TCE degradation due to precipitation of secondary carbonate minerals, as indicated by a higher value for the ratio of maximum to minimum TCE degradation rate observed over time. From the calculated branching ratios, it was found that TCE and cis-dichloroethene (cis-DCE) were dominantly dechlorinated to chloroacetylene and acetylene, respectively, through reductive elimination for both columns. The CMM model, validated by the column test data in this study, provides a convenient tool to determine simultaneously the critical design parameters for permeable reactive barriers and natural attenuation such as rate constants and branching ratios. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Determination of rate constants and branching ratios for TCE degradation by zero-valent iron using a chain decay multispecies model

    Science.gov (United States)

    Hwang, Hyoun-Tae; Jeen, Sung-Wook; Sudicky, Edward A.; Illman, Walter A.

    2015-06-01

    The applicability of a newly-developed chain-decay multispecies model (CMM) was validated by obtaining kinetic rate constants and branching ratios along the reaction pathways of trichloroethene (TCE) reduction by zero-valent iron (ZVI) from column experiments. Changes in rate constants and branching ratios for individual reactions for degradation products over time for two columns under different geochemical conditions were examined to provide ranges of those parameters expected over the long-term. As compared to the column receiving deionized water, the column receiving dissolved CaCO3 showed higher mean degradation rates for TCE and all of its degradation products. However, the column experienced faster reactivity loss toward TCE degradation due to precipitation of secondary carbonate minerals, as indicated by a higher value for the ratio of maximum to minimum TCE degradation rate observed over time. From the calculated branching ratios, it was found that TCE and cis-dichloroethene (cis-DCE) were dominantly dechlorinated to chloroacetylene and acetylene, respectively, through reductive elimination for both columns. The CMM model, validated by the column test data in this study, provides a convenient tool to determine simultaneously the critical design parameters for permeable reactive barriers and natural attenuation such as rate constants and branching ratios.

  7. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    Energy Technology Data Exchange (ETDEWEB)

    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  8. A mathematical model to determine molecular kinetic rate constants under non-steady state conditions using fluorescence recovery after photobleaching (FRAP).

    Science.gov (United States)

    Lele, Tanmay P; Ingber, Donald E

    2006-03-01

    Fluorescence recovery after photobleaching (FRAP) analyses of binding and unbinding of molecules that interact with insoluble scaffolds, such as the cytoskeleton and nuclear matrix, in living cells commonly assume that this process is at equilibrium over the time scale of fluorescence recovery. This assumption breaks down for relatively fast intracellular processes like focal adhesion assembly at the leading edge of a migrating cell, or changes of transcriptional activation in the nucleus, that can occur in a matter of a few minutes. In this paper, we formulate a mathematical model that permits FRAP to be used to determine kinetic rate constants of molecules that interact with insoluble cellular structures under non-steady state conditions. We show that unlike steady state FRAP, fluorescence recovery time scales under these unsteady conditions are determined not only by unbinding rates, but also by the overall assembly and disassembly dynamics of the structural scaffold which supports these binding interactions. Experimental data from FRAP analysis and quantification of scaffold assembly dynamics may be combined and used with our mathematical model to estimate kinetic rate constants, as well as the apparent rate constant of scaffold assembly and disassembly.

  9. State-to-state rotational relaxation rate constants for CO+Ne from IR-IR double-resonance experiments: comparing theory to experiment.

    Science.gov (United States)

    Hostutler, David A; Smith, Tony C; Hager, Gordon D; McBane, George C; Heaven, Michael C

    2004-04-22

    IR-IR double-resonance experiments were used to study the state-to-state rotational relaxation of CO with Ne as a collision partner. Rotational levels in the range Ji=2-9 were excited and collisional energy transfer of population to the levels Jf=2-8 was monitored. The resulting data set was analyzed by fitting to numerical solutions of the master equation. State-to-state rate constant matrices were generated using fitting law functions. Fitting laws based on the modified exponential gap (MEG) and statistical power exponential gap (SPEG) models were used; the MEG model performed better than the SPEG model. A rate constant matrix was also generated from scattering calculations that employed the ab initio potential energy surface of McBane and Cybulski [J. Chem. Phys. 110, 11 734 (1999)]. This theoretical rate constant matrix yielded kinetic simulations that agreed with the data nearly as well as the fitted MEG model and was unique in its ability to reproduce both the rotational energy transfer and pressure broadening data for Ne-CO. The theoretical rate coefficients varied more slowly with the energy gap than coefficients from either of the fitting laws. (c) 2004 American Institute of Physics

  10. Low temperature rate constants for the N(4S) + CH(X2Πr) reaction. Implications for N2 formation cycles in dense interstellar clouds.

    Science.gov (United States)

    Daranlot, Julien; Hu, Xixi; Xie, Changjian; Loison, Jean-Christophe; Caubet, Philippe; Costes, Michel; Wakelam, Valentine; Xie, Daiqian; Guo, Hua; Hickson, Kevin M

    2013-09-07

    Rate constants for the potentially important interstellar N((4)S) + CH(X(2)Πr) reaction have been measured in a continuous supersonic flow reactor over the range 56 K ≤T≤ 296 K using the relative rate technique employing both the N((4)S) + OH(X(2)Πi) and N((4)S) + CN(X(2)Σ(+)) reactions as references. Excess concentrations of atomic nitrogen were produced by the microwave discharge method upstream of the Laval nozzle and CH and OH radicals were created by the in situ pulsed laser photolysis of suitable precursor molecules. In parallel, quantum dynamics calculations of the title reaction have been performed based on accurate global potential energy surfaces for the 1(3)A' and 1(3)A'' states of HCN and HNC, brought about through a hierarchical construction scheme. Both adiabatic potential energy surfaces are barrierless, each one having two deep potential wells suggesting that this reaction is dominated by a complex-forming mechanism. The experimental and theoretical work are in excellent agreement, predicting a positive temperature dependence of the rate constant, in contrast to earlier experimental work at low temperature. The effects of the new low temperature rate constants on interstellar N2 formation are tested using a dense cloud model, yielding N2 abundances 10-20% lower than previously predicted.

  11. New ab initio potential energy surface for BrH2 and rate constants for the H + HBr → H2 + Br abstraction reaction.

    Science.gov (United States)

    Jiang, Bin; Xie, Changjian; Xie, Daiqian

    2011-03-21

    A global potential energy surface (PES) for the electronic ground state of the BrH(2) system was constructed based on the multireference configuration interaction (MRCI) method including the Davidson's correction using a large basis set. In addition, the spin-orbit correction were computed using the Breit-Pauli Hamiltonian and the unperturbed MRCI wavefunctions in the Br + H(2) channel and the transition state region. Adding the correction to the ground state potential, the lowest spin-orbit correlated adiabatic potential was obtained. The characters of the new potential are discussed. Accurate initial state specified rate constants for the H + HBr → H(2) + Br abstraction reaction were calculated using a time-dependent wave packet method. The predicted rate constants were found to be in excellent agreement with the available experimental values and much better than those obtained from a previous PES.

  12. Upper limits for the rate constants of the reactions of CF3O2 and CF3O radicals with ozone at 295 K

    DEFF Research Database (Denmark)

    Nielsen, O.J.; Sehested, J.

    1993-01-01

    Using the pulse radiolysis UV absorption technique and subsequent simulations of experimental absorption transients at 254 and 276 nm, upper limits of the rate constants for the reactions of CF3O2 and CF3O radicals with ozone were determined at 295 K, CF3O2+O3-->CF3O+2O2 (4), CF3O+O3-->CF3O2+O2 (......). The upper limits were derived as k4 ozone depletion by hydrofluorocarbons.......Using the pulse radiolysis UV absorption technique and subsequent simulations of experimental absorption transients at 254 and 276 nm, upper limits of the rate constants for the reactions of CF3O2 and CF3O radicals with ozone were determined at 295 K, CF3O2+O3-->CF3O+2O2 (4), CF3O+O3-->CF3O2+O2 (5...

  13. The chemistry of bromine in the stratosphere: Influence of a new rate constant for the reaction BrO + HO2

    Science.gov (United States)

    Pirre, Michel; Marceau, Francois J.; Lebras, Georges; Maguin, Francoise; Poulet, Gille; Ramaroson, Radiela

    1994-01-01

    The impact of new laboratory data for the reaction BrO + HO2 yields HOBr + O2 in the depletion of global stratospheric ozone has been estimated using a one-dimensional photochemical model taking into account the heterogeneous reaction on sulphate aerosols which converts N2O5 into HNO3. Assuring an aerosol loading 2 times as large as the 'background' and a reaction probability of 0.1 for the above heterogeneous reaction, the 6 fold increase in the measured rate constant for the reaction of BrO with HO2 increases the computed depletion of global ozone produced by 20 ppt of total bromine from 2.01 percent to 2.36 percent. The use of the higher rate constant increases the HOBr mixing ratio and makes the bromine partitioning and the ozone depletion very sensitive to the branching ratio of the potential channel forming HBr in the BrO + HO2 reaction.

  14. Constant harvest rate for the Pacific sardine (Sardinops caeruleus) fishery in the Gulf of California based on catchability-at-length estimations

    OpenAIRE

    Martínez Aguilar, Susana; de Anda Montañez, Juan Antonio; Arreguín Sánchez, Francisco; Cisneros Mara, Miguel Angel

    2009-01-01

    Constant harvest rate as a management strategy for the Pacific sardine (Sardinops caeruleus) fishery in the Gulf of California is supported by an analysis of variations in the catchability coefficient (q), stock abundance and commercial catch. Catchability was analyzed based on population length-structured data standard length (SL), expressed as CPUE, for 26 fishing seasons (1972-1973 to 1997-1998). We used a deterministic model of catchability to estimate the catchability-at-length assuming ...

  15. Energy disposal and thermal rate constants for the OH + HBr and OH + DBr reactions: quasiclassical trajectory calculations on an accurate potential energy surface.

    Science.gov (United States)

    de Oliveira-Filho, Antonio G S; Ornellas, Fernando R; Bowman, Joel M

    2014-12-26

    We report reaction cross sections, energy disposal, and rate constants for the OH + HBr → Br + H2O and OH + DBr → Br + HDO reactions from quasiclassical trajectory calculations using an ab initio potential energy surface [ de Oliveira-Filho , A. G. S. ; Ornellas , F. R. ; Bowman , J. M. J. Phys. Chem. Lett. 2014 , 5 , 706 - 712 ]. Comparison with available experiments are made and generally show good agreement.

  16. Absolute rate constants for the reaction of CF3O2 and CF3O radicals with NO at 295 K

    DEFF Research Database (Denmark)

    Sehested, J.; Nielsen, O.J.

    1993-01-01

    Using a pulse radiolysis UV absorption technique and subsequent simulations of experimental NO2 and FNO absorption transients, rate constants for reaction between CF3O and CF3O2 radicals with NO were determined, CF3O2+NO-->CF3O+NO2 (3), CF3O+NO-->CF2O+FNO (5). k3 was derived to be (1.68+/-0.26)x10...

  17. Behavioural Phenotyping of APPswe/PS1δE9 Mice: Age-Rrelated Changes and Effect of Long-Term Paroxetine Treatment.

    Science.gov (United States)

    Olesen, Louise Ørum; Bouzinova, Elena V; Severino, Maurizio; Sivasaravanaparan, Mithula; Hasselstrøm, Jørgen Bo; Finsen, Bente; Wiborg, Ove

    2016-01-01

    Alzheimer's disease (AD) is a devastating illness characterized by a progressive loss of cognitive, social, and emotional functions, including memory impairments and more global cognitive deficits. Clinical-epidemiological evidence suggests that neuropsychiatric symptoms precede the onset of cognitive symptoms both in humans with early and late onset AD. The behavioural profile promoted by the AD pathology is believed to associate with degeneration of the serotonergic system. Using the APPswe/PS1δE9 model of AD-like pathology starting with 9 months old mice, we characterised long term non-cognitive behavioural changes measured at 9, 12, 15, and 18 months of age and applied principal component analysis on data obtained from open field, elevated plus maze, and social interaction tests. Long-term treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine was applied to assess the role of 5-HT on the behavioural profile; duration of treatment was 9 months, initiated when mice were 9 months of age. Treatment with paroxetine delays the decline in locomotion, in exploration and risk assessment behaviour, found in the APP/PS1 mice. APP/PS1 mice also exhibit low social activity and less aggressiveness, both of which are not affected by treatment with paroxetine. The APP/PS1 behavioural phenotype, demonstrated in this study, only begins to manifest itself from 12 months of age. Our results indicate that treatment with SSRI might ameliorate some of the behavioural deficits found in aged APP/PS1 mice.

  18. Rate constant for the H˙ + H2O → ˙OH + H2reaction at elevated temperatures measured by pulse radiolysis.

    Science.gov (United States)

    Muroya, Y; Yamashita, S; Lertnaisat, P; Sanguanmith, S; Meesungnoen, J; Jay-Gerin, J-P; Katsumura, Y

    2017-11-22

    Maintaining the structural integrity of materials in nuclear power plants is an essential issue associated with safe operation. Hydrogen (H 2 ) addition or injection to coolants is a powerful technique that has been widely applied such that the reducing conditions in the coolant water avoid corrosion and stress corrosion cracking (SCC). Because the radiation-induced reaction of ˙OH + H 2 → H˙ + H 2 O plays a crucial role in these systems, the rate constant has been measured at operation temperatures of the reactors (285-300 °C) by pulse radiolysis, generating sufficient data for analysis. The reverse reaction H˙ + H 2 O → ˙OH + H 2 is negligibly slow at ambient temperature; however, it accelerates considerably quickly at elevated temperatures. Although the reverse reaction reduces the effectiveness of H 2 addition, reliable rate constants have not yet been measured. In this study, the rate constants have been determined in a temperature range of 250-350 °C by pulse radiolysis in an aqueous I - solution.

  19. Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

    Science.gov (United States)

    Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

    2012-01-01

    Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

  20. QSAR models for oxidation of organic micropollutants in water based on ozone and hydroxyl radical rate constants and their chemical classification

    KAUST Repository

    Sudhakaran, Sairam

    2013-03-01

    Ozonation is an oxidation process for the removal of organic micropollutants (OMPs) from water and the chemical reaction is governed by second-order kinetics. An advanced oxidation process (AOP), wherein the hydroxyl radicals (OH radicals) are generated, is more effective in removing a wider range of OMPs from water than direct ozonation. Second-order rate constants (kOH and kO3) are good indices to estimate the oxidation efficiency, where higher rate constants indicate more rapid oxidation. In this study, quantitative structure activity relationships (QSAR) models for O3 and AOP processes were developed, and rate constants, kOH and kO3, were predicted based on target compound properties. The kO3 and kOH values ranged from 5 * 10-4 to 105 M-1s-1 and 0.04 to 18 * (109) M-1 s-1, respectively. Several molecular descriptors which potentially influence O3 and OH radical oxidation were identified and studied. The QSAR-defining descriptors were double bond equivalence (DBE), ionisation potential (IP), electron-affinity (EA) and weakly-polar component of solvent accessible surface area (WPSA), and the chemical and statistical significance of these descriptors was discussed. Multiple linear regression was used to build the QSAR models, resulting in high goodness-of-fit, r2 (>0.75). The models were validated by internal and external validation along with residual plots. © 2012 Elsevier Ltd.

  1. Estrogen Modulates ubc9 Expression and Synaptic Redistribution in the Brain of APP/PS1 Mice and Cortical Neurons.

    Science.gov (United States)

    Lai, Yu-Jie; Liu, Lu; Hu, Xiao-Tong; He, Ling; Chen, Guo-Jun

    2017-03-01

    Estrogen exerts multiple actions in the brain and is an important neuroprotective factor in a number of neuronal disorders. However, the underlying mechanism remains unknown. Studies demonstrate that ubiquitin-conjugating enzyme 9 (ubc9) has an integral role in synaptic plasticity and may contribute to the pathology of neuronal disorders. We aimed to investigate the effects of estrogen on ubc9 and in the Alzheimer's disease brain. Ubc9 protein and mRNA were significantly increased in the cortex and hippocampus of APP/PS1 mice with enhanced SUMOylation. Systemic estrogen administration led to reduced ubc9 expression in ovariectomized APP/PS1 mice and reduced SUMOylation. The inhibition of ubc9 expression by estrogen was found to be dose-dependent in cultured neurons. However, estrogen receptor (ER) antagonist ICI182780 did not block the inhibition of ubc9 expression by estrogen. Furthermore, the reduced expression of ubc9 was not mediated by ERα or ERβ agonists alone or in combination, but by the membrane-impermeable ER agonist E2-bovine serum albumin. The activation of the G protein-coupled ER mediated the inhibition of ubc9 expression of estrogen. A phosphoinositide 3-kinase (PI3K) inhibitor, rather than an extracellular signal-regulated kinase inhibitor, blocked the inhibition of ubc9 by estrogen. Estrogen treatment significantly increased the phosphorylation of PI3K, which suggests that activation of the PI3K pathway by estrogen is required for ubc9 regulation. Further, ubc9 interacted with the synaptic proteins post-synaptic density protein 95 (PSD95) and synaptophysin. Estrogen decreased the interaction of ubc9 with post-synaptic PSD95, but increased the interaction of ubc9 with pre-synaptic synaptophysin. These results suggest that a membrane-bound ER might mediate the estrogen inhibition of ubc9 in cortical neurons, where PI3K plays an important role. We also show that ubc9 can interact with synaptic proteins, which are subject to estrogen regulation.

  2. Chronic stress induced cognitive impairment in APP/PS-1 double transgenic mouse model of Alzheimer's disease

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    Bing HAN

    2015-08-01

    Full Text Available Objective  To observe the effect of chronic unpredictable mild stress (CUMS on the cognitive function and brain morphological changes in APP/PS-1 mice, one of the genetic mouse models of Alzheimer's disease (AD, and to investigate the possible role of environmental factors in genetic mouse model of AD. Methods  There were 22-week-old wild-type C57BL/6 male mice (control group, N = 15 and APP/PS-1 double transgenic male mice [N = 27: AD group (N = 13 and AD + CUMS group (N = 14] tested in this study. Morris water maze test was used to evaluate spatial learning and memory of the mice. Amyloid deposition in the hippocampus was determined by Congo red staining. The ultrastructure of neurons in hippocampal CA1 region was observed by transmission electron microscope (TEM.  Results  Compared with control group, AD + CUMS group had significantly longer fifth-day escape latency [(33.14 ± 14.37 s vs (21.22 ± 12.16 s; t = -2.701, P = 0.045], and significantly shortened time spent in platform quadrant [(9.74±1.35 s vs (15.02 ± 1.33 s; t = 2.639, P = 0.012] in Morris water maze test. Compared with AD group, the percentage of amyloid plaque area in hippocampal area was increased in AD + CUMS group [(0.59 ± 0.03% vs (0.04 ± 0.03%; t = -2.900, P = 0.005]. The ultrastructure of hippocampal neurons in AD group was slightly damaged: cellular membrane was intact; cell matrix was uniform; intracelluar lipofuscin could be seen; the structure of nucleus and nuclear membrane had no obvious changes; mild fusion of cristae and membrane was seen in mitochondria; Golgi apparatus was partially indistinct; endoplasmic reticulum was mildly expanded. The ultrastructure of hippocampal neurons in AD + CUMS group was obviously damaged, including blurred cell membrane, reduced low-density and high-density granules in cytoplasm, uneven cell matrix, reduced number of organelles, lipofuscin and autophagosome deposition, obvious condensation of chromatin distributing over

  3. Laboratory Measurement of the Gas-Phase Rate Constant for Formation of Nitric Acid from the Reaction of OH and NO2

    Science.gov (United States)

    Mollner, A. K.; Feng, L.; Sprague, M. K.; Okumura, M.; Vallavudasan, S.; Sander, S. P.; Martien, P. T.; Harley, R. A.; McCoy, A. B.

    2007-12-01

    The rate constant for the reaction OH + NO2 + M → HONO2 + M is among the most influential parameters affecting air pollution levels. There remains significant uncertainty about this rate, due to lack of laboratory data at 1 atm and to the unknown yield of a secondary channel forming peroxynitrous acid (HOONO). New experimental measurements of both the kinetics and HOONO/HONO2 branching ratios at 760 Torr are presented. The results are compared with current recommendations; when incorporated in models, the new parameters lead to significantly higher modeled ozone levels and reduced formation of nitric acid.

  4. Reaction rate constant of CH2O + H = HCO + H2 revisited: a combined study of direct shock tube measurement and transition state theory calculation.

    Science.gov (United States)

    Wang, Shengkai; Dames, Enoch E; Davidson, David F; Hanson, Ronald K

    2014-11-06

    The rate constant of the H-abstraction reaction of formaldehyde (CH2O) by hydrogen atoms (H), CH2O + H = H2 + HCO, has been studied behind reflected shock waves with use of a sensitive mid-IR laser absorption diagnostic for CO, over temperatures of 1304-2006 K and at pressures near 1 atm. C2H5I was used as an H atom precursor and 1,3,5-trioxane as the CH2O precursor, to generate a well-controlled CH2O/H reacting system. By designing the experiments to maintain relatively constant H atom concentrations, the current study significantly boosted the measurement sensitivity of the target reaction and suppressed the influence of interfering reactions. The measured CH2O + H rate constant can be expressed in modified Arrhenius from as kCH2O+H(1304-2006 K, 1 atm) = 1.97 × 10(11)(T/K)(1.06) exp(-3818 K/T) cm(3) mol(-1)s(-1), with uncertainty limits estimated to be +18%/-26%. A transition-state-theory (TST) calculation, using the CCSD(T)-F12/VTZ-F12 level of theory, is in good agreement with the shock tube measurement and extended the temperature range of the current study to 200-3000 K, over which a modified Arrhenius fit of the rate constant can be expressed as kCH2O+H(200-3000 K) = 5.86 × 10(3)(T/K)(3.13) exp(-762 K/T) cm(3) mol(-1)s(-1).

  5. Rate constants for collisional quenching of NO (A(2)Σ(+), v = 0) by He, Ne, Ar, Kr, and Xe, and infrared emission accompanying rare gas and impurity quenching.

    Science.gov (United States)

    Few, Julian; Hancock, Gus

    2014-06-14

    The quenching rates of NO (A(2)Σ(+), v = 0) with He, Ne, Ar, Kr and Xe have been studied at room temperature by measurements of the time dependence of the fluorescence decay following laser excitation. The rates are slow, with upper limits of rate constants determined as between 1.2 and 2.0 × 10(-14) cm(3) molecule(-1) s(-1), considerably lower than those reported before in the literature. Such slow rates can be markedly influenced by impurities such as O2 and H2O which have quenching rate constants close to gas kinetic values. Time resolved Fourier transform infrared emission has been used to observe the products of the quenching processes with the rare gases and with impurities. For He, Ne Ar and Kr there is no difference within experimental error of the populations in NO (X(2)Π v ≥ 2) produced with and without rare gas present, but the low quantum yields of such quenching (of the order of 5% for an atmosphere of rare gas) preclude quantitative information on the quantum states being obtained. For quenching by Xe the collisional formation of electronically excited Xe atoms dominates the emission at early times. Vibrationally excited NO (X(2)Π, v) and products of reactive quenching are observed in the presence of O2 and H2O.

  6. Learning rates and known-to-unknown flash-card ratios: comparing effectiveness while holding instructional time constant.

    Science.gov (United States)

    Forbes, Bethany E; Skinner, Christopher H; Black, Michelle P; Yaw, Jared; Booher, Joshua; Delisle, Jean

    2013-12-01

    Using alternating treatments designs, we compared learning rates across 2 computer-based flash-card interventions (3 min each): a traditional drill intervention with 15 unknown words and an interspersal intervention with 12 known words and 3 unknown words. Each student acquired more words under the traditional drill intervention. Discussion focuses on the need to account for instructional time when learning procedures are evaluated and compared. © Society for the Experimental Analysis of Behavior.

  7. Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice.

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    Simona Capsoni

    Full Text Available Nerve Growth Factor (NGF is being considered as a therapeutic candidate for Alzheimer's disease (AD treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V, which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8, hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.

  8. Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice.

    Science.gov (United States)

    Capsoni, Simona; Marinelli, Sara; Ceci, Marcello; Vignone, Domenico; Amato, Gianluca; Malerba, Francesca; Paoletti, Francesca; Meli, Giovanni; Viegi, Alessandro; Pavone, Flaminia; Cattaneo, Antonino

    2012-01-01

    Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.

  9. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice.

    Science.gov (United States)

    Aso, Ester; Juvés, Salvador; Maldonado, Rafael; Ferrer, Isidro

    2013-01-01

    The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a genetic model of Alzheimer's disease. This effect was more pronounced when administered at the pre-symptomatic rather than the early symptomatic stage. The cognitive improvement was associated with decreased microglial reactivity and reduced expression of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and IFNγ. In addition, JWH-133 reduced the expression of active p38 and SAPK/JNK, increased the expression of inactive GSK3β, and lowered tau hyperphosphorylation at Thr181 in the vicinity of amyloid-β plaques. Moreover, JWH-133 produced a decrease in the expression of hydroxynonenal adducts, and enhanced the expression of SOD1 and SOD2 around plaques. In contrast, the chronic treatment with JWH-133 failed to modify the amyloid-β production or deposition in cortex and hippocampus. In conclusion, the present study lends support to the idea that stimulation of CB2 receptors ameliorates several altered parameters in Alzheimer's disease such as impaired memory and learning, neuroinflammation, oxidative stress damage and oxidative stress responses, selected tau kinases, and tau hyperphosphorylation around plaques.

  10. Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways

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    Miren Ettcheto

    2017-10-01

    Full Text Available The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI, in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42 plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.

  11. NLRP3 is activated in Alzheimer´s disease and contributes to pathology in APP/PS1 mice

    Science.gov (United States)

    Heneka, Michael T.; Kummer, Markus P.; Stutz, Andrea; Delekate, Andrea; Schwartz, Stephanie; Saecker, Ana; Griep, Angelika; Axt, Daisy; Remus, Anita; Tzeng, Te-Chen; Gelpi, Ellen; Halle, Annett; Korte, Martin; Latz, Eicke; Golenbock, Douglas

    2013-01-01

    Alzheimer´s Disease (AD) is the world’s most common dementing illness. Deposition of amyloid beta peptide (Aβ) drives cerebral neuroinflammation by activating microglia1,2. Indeed, Aβ activation of the NLRP3 inflammasome in microglia is fundamental for IL-1β maturation and subsequent inflammatory events3. However, it remains unknown whether NLRP3 activation contributes to AD in vivo. Here, we demonstrate strongly enhanced active caspase-1 expression in human MCI and AD brains suggesting a role for the inflammasome in this neurodegenerative disease. NLRP3−/− or caspase-1−/− mice carrying mutations associated with familiar AD were largely protected from loss of spatial memory and other AD-associated sequelae and demonstrated reduced brain caspase-1 and IL-1β activation as well as enhanced Aβ clearance. Furthermore, NLRP3 inflammasome deficiency skewed microglial cells to an M2 phenotype and resulted in the decreased deposition of Aβ in the APP/PS1 model of Alzheimer’s disease. These results reveal an important role for the NLRP3 / caspase-1 axis in AD pathogenesis, and suggest that NLRP3 inflammasome inhibition represents a novel therapeutic intervention for AD. PMID:23254930

  12. Quantum instanton calculation of rate constant for CH4 + OH → CH3 + H2O reaction: torsional anharmonicity and kinetic isotope effect.

    Science.gov (United States)

    Wang, Wenji; Zhao, Yi

    2012-12-07

    Thermal rate constants for the title reaction are calculated by using the quantum instanton approximation within the full dimensional Cartesian coordinates. The results reveal that the quantum effect is remarkable for the reaction at both low and high temperatures, and the obtained rates are in good agreement with experimental measurements at high temperatures. Compared to the harmonic approximation, the torsional anharmonic effect of the internal rotation has a little influence on the rates at low temperatures, however, it enhances the rate by about 20% at 1000 K. In addition, the free energy barriers for the isotopic reactions and the temperature dependence of kinetic isotope effects are also investigated. Generally speaking, for the title reaction, the replacement of OH with OD will reduce the free energy barrier, while substituting D for H (connected to C) will increase the free energy barrier.

  13. Do Insect Populations Die at Constant Rates as They Become Older? Contrasting Demographic Failure Kinetics with Respect to Temperature According to the Weibull Model.

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    Petros Damos

    Full Text Available Temperature implies contrasting biological causes of demographic aging in poikilotherms. In this work, we used the reliability theory to describe the consistency of mortality with age in moth populations and to show that differentiation in hazard rates is related to extrinsic environmental causes such as temperature. Moreover, experiments that manipulate extrinsic mortality were used to distinguish temperature-related death rates and the pertinence of the Weibull aging model. The Newton-Raphson optimization method was applied to calculate parameters for small samples of ages at death by estimating the maximum likelihoods surfaces using scored gradient vectors and the Hessian matrix. The study reveals for the first time that the Weibull function is able to describe contrasting biological causes of demographic aging for moth populations maintained at different temperature regimes. We demonstrate that at favourable conditions the insect death rate accelerates as age advances, in contrast to the extreme temperatures in which each individual drifts toward death in a linear fashion and has a constant chance of passing away. Moreover, slope of hazard rates shifts towards a constant initial rate which is a pattern demonstrated by systems which are not wearing out (e.g. non-aging since the failure, or death, is a random event independent of time. This finding may appear surprising, because, traditionally, it was mostly thought as rule that in aging population force of mortality increases exponentially until all individuals have died. Moreover, in relation to other studies, we have not observed any typical decelerating aging patterns at late life (mortality leveling-off, but rather, accelerated hazard rates at optimum temperatures and a stabilized increase at the extremes.In most cases, the increase in aging-related mortality was simulated reasonably well according to the Weibull survivorship model that is applied. Moreover, semi log- probability hazard

  14. Do Insect Populations Die at Constant Rates as They Become Older? Contrasting Demographic Failure Kinetics with Respect to Temperature According to the Weibull Model.

    Science.gov (United States)

    Damos, Petros; Soulopoulou, Polyxeni

    2015-01-01

    Temperature implies contrasting biological causes of demographic aging in poikilotherms. In this work, we used the reliability theory to describe the consistency of mortality with age in moth populations and to show that differentiation in hazard rates is related to extrinsic environmental causes such as temperature. Moreover, experiments that manipulate extrinsic mortality were used to distinguish temperature-related death rates and the pertinence of the Weibull aging model. The Newton-Raphson optimization method was applied to calculate parameters for small samples of ages at death by estimating the maximum likelihoods surfaces using scored gradient vectors and the Hessian matrix. The study reveals for the first time that the Weibull function is able to describe contrasting biological causes of demographic aging for moth populations maintained at different temperature regimes. We demonstrate that at favourable conditions the insect death rate accelerates as age advances, in contrast to the extreme temperatures in which each individual drifts toward death in a linear fashion and has a constant chance of passing away. Moreover, slope of hazard rates shifts towards a constant initial rate which is a pattern demonstrated by systems which are not wearing out (e.g. non-aging) since the failure, or death, is a random event independent of time. This finding may appear surprising, because, traditionally, it was mostly thought as rule that in aging population force of mortality increases exponentially until all individuals have died. Moreover, in relation to other studies, we have not observed any typical decelerating aging patterns at late life (mortality leveling-off), but rather, accelerated hazard rates at optimum temperatures and a stabilized increase at the extremes.In most cases, the increase in aging-related mortality was simulated reasonably well according to the Weibull survivorship model that is applied. Moreover, semi log- probability hazard rate model

  15. Differentiating inflamed and normal lungs by the apparent reaction rate constants of lactate dehydrogenase probed by hyperpolarized (13)C labeled pyruvate.

    Science.gov (United States)

    Xu, He N; Kadlececk, Stephen; Shaghaghi, Hoora; Zhao, Huaqing; Profka, Harilla; Pourfathi, Mehrdad; Rizi, Rahim; Li, Lin Z

    2016-02-01

    Clinically translatable hyperpolarized (HP) (13)C-NMR can probe in vivo enzymatic reactions, e.g., lactate dehydrogenase (LDH)-catalyzed reaction by injecting HP (13)C-pyruvate into the subject, which is converted to (13)C labeled lactate by the enzyme. Parameters such as (13)C-lactate signals and lactate-to-pyruvate signal ratio are commonly used for analyzing the HP (13)C-NMR data. However, the biochemical/biological meaning of these parameters remains either unclear or dependent on experimental settings. It is preferable to quantify the reaction rate constants with a clearer physical meaning. Here we report the extraction of the kinetic parameters of the LDH reaction from HP (13)C-NMR data and investigate if they can be potential predictors of lung inflammation. Male Sprague-Dawley rats (12 controls, 14 treated) were used. One dose of bleomycin (2.5 U/kg) was administered intratracheally to the treatment group. The lungs were removed, perfused, and observed by the HP-NMR technique, where a HyperSense dynamic nuclear polarization system was used to generate the HP (13)C-pyruvate for injecting into the lungs. A 20 mm (1)H/(13)C dual-tuned coil in a 9.4-T Varian vertical bore NMR spectrometer was employed to acquire the (13)C spectral data every 1 s over a time period of 300 s using a non-selective, 15-degree radiofrequency pulse. The apparent rate constants of the LDH reaction and their ratio were quantified by applying ratiometric fitting analysis to the time series data of (13)C labeled pyruvate and lactate. The apparent forward rate constant kp =(3.67±3.31)×10(-4) s(-1), reverse rate constant kl =(4.95±2.90)×10(-2) s(-1), rate constant ratio kp /kl =(7.53±5.75)×10(-3) for the control lungs; kp =(11.71±4.35)×10(-4) s(-1), kl =(9.89±3.89)×10(-2) s(-1), and kp /kl =(12.39±4.18)×10(-3) for the inflamed lungs at the 7(th) day post treatment. Wilcoxon rank-sum test showed that the medians of these kinetic parameters of the 7-day cohort were significantly

  16. Using Optical Oxygen Sensors and Injection Experiments to Determine in situ Microbial Rate Constants for Methane Oxidation and Heterotrophic Respiration in a Boreal Bog and Fen

    Science.gov (United States)

    Waldo, N.; Moorberg, C.; Waldrop, M. P.; Turetsky, M. R.; Neumann, R. B.

    2015-12-01

    Wetlands are the largest natural source of methane to the atmosphere, and play a key role in feedback cycles to climate change. In recognition of this, many researchers are developing process-based models of wetland methane emissions at various scales. In these models, the three key biogeochemical reactions are methane production, methane oxidation, and heterotrophic respiration, and they are modeled using Michaelis-Menten kinetics. The majority of Michaelis-Menten rate constants used in models are based on experiments involving slurries of peat incubated in vials. While these slurries provide a highly controlled setting, they are different from in situ conditions in multiple ways; notably they lack live plants and the centimeter-scale heterogeneities that exist in the field. To determine rate constants in a system more representative of in situ conditions, we extracted peat cores intact from a bog and fen located in the Bonanza Creek Experimental Forest near Fairbanks, Alaska and part of the Alaska Peatland Experiment (APEX) research program. Into those cores we injected water with varying concentrations of methane and oxygen at multiple depths. We used planar oxygen sensors installed on the peat cores to collect high resolution, two dimensional oxygen concentration data during the injections and used oxygen consumption rates under various conditions to calculate rate constants. Results were compared to a similar but smaller set of injection experiments conducted against planar oxygen sensors installed in the bog. Results will inform parametrization of microbial processes in wetland models, improving estimates of methane emissions both under current climate conditions and in the future.

  17. Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin.

    Science.gov (United States)

    Lowrie, M; Thomson, S; Smith, P; Garosi, L

    2016-07-01

    Administration of cytosine arabinoside (CA) by continuous rate infusion (CRI) has pharmacokinetic and pharmacodynamic advantages over traditional intermittent dosing. Whether these advantages translate into clinical efficacy remains unknown. The aim of this study was to assess the efficacy and safety of CRI of CA in dogs with meningoencephalitis of unknown origin (MUO) and to compare outcomes with a group of historical control dogs treated with conventional intermittent subcutaneous (SC) administration of CA; both groups received adjunctive prednisolone. It was hypothesised that a CRI of CA for 24 h at 100 mg/m(2) would improve survival and lesion resolution compared with conventional SC delivery of 50 mg/m(2) every 12 h for 48 h. Eighty dogs with suspected MUO were recruited from consecutive dogs presenting with suspected MUO from 2006 to 2015. All dogs underwent routine clinical evaluation, magnetic resonance imaging of the brain and cerebrospinal fluid analysis. There were 39 dogs in the SC group and 41 dogs in the CRI group; baseline characteristics were similar in both groups. Survival at 3 months was 22/39 (44%) with SC delivery versus 37/41 (90%) with CRI. No dose-limiting toxicities were noted for either group. The resolution rate of magnetic resonance imaging and cerebrospinal fluid abnormalities at the 3 month re-examination were substantially improved in the CRI group versus the SC group. The CRI regimen produced a survival advantage over the SC route of administration without clinically significant toxicity. These data supports the routine use of CRI at first presentation for the treatment of MUO in dogs. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  18. Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on cardiopulmonary function and depth of anesthesia in horses anesthetized with isoflurane.

    Science.gov (United States)

    Creighton, Catherine M; Lemke, Kip A; Lamont, Leigh A; Horney, Barbara S; Riley, Christopher B

    2012-04-15

    To compare the effects of xylazine bolus versus medetomidine constant rate infusion (MCRI) on cardiopulmonary function and depth of anesthesia in dorsally recumbent, spontaneously breathing, isoflurane-anesthetized horses. Prospective, randomized crossover study. 10 healthy adult Standardbreds. Horses were premedicated with xylazine or medetomidine IV. Anesthesia was induced with diazepam and ketamine and maintained with isoflurane for 150 minutes. For the xylazine treatment, end-tidal isoflurane concentration was maintained at 1.7%, and xylazine (0.2 mg/kg [0.09 mg/lb], IV) was administered as a bolus at the end of anesthesia. For the MCRI treatment, end-tidal isoflurane concentration was maintained at 1.4%, and medetomidine (0.005 mg/kg/h [0.0023 mg/lb/h], IV) was infused throughout anesthesia. Physiologic data (ie, heart rate, respiratory rate, rectal temperature, bispectral index, and electromyographic values) were compared between treatments with xylazine bolus versus MCRI. Heart rate was lower, but mean arterial blood pressure was higher from 20 to 40 minutes with MCRI treatment, compared with conventional treatment with xylazine. Respiratory rate and rectal temperature were greater with MCRI treatment. Bispectral index was lower with MCRI treatment from 80 to 150 minutes, and electromyographic values were lower with MCRI treatment from 30 to 150 minutes. In isoflurane-anesthetized horses, premedication with medetomidine followed by administration of medetomidine as a constant rate infusion resulted in decreased heart rate, higher arterial blood pressure from 20 through 40 minutes after induction of anesthesia, and better preserved body temperature, compared with conventional treatment with xylazine. Greater depth of anesthesia and muscle relaxation were seen with MCRI treatment, despite the lower isoflurane concentration.

  19. Nonmonotonic Temperature Dependence of the Pressure-Dependent Reaction Rate Constant and Kinetic Isotope Effect of Hydrogen Radical Reaction with Benzene Calculated by Variational Transition-State Theory.

    Science.gov (United States)

    Zhang, Hui; Zhang, Xin; Truhlar, Donald G; Xu, Xuefei

    2017-11-30

    The reaction between H and benzene is a prototype for reactions of radicals with aromatic hydrocarbons. Here we report calculations of the reaction rate constants and the branching ratios of the two channels of the reaction (H addition and H abstraction) over a wide temperature and pressure range. Our calculations, obtained with an accurate potential energy surface, are based on variational transition-state theory for the high-pressure limit of the addition reaction and for the abstraction reaction and on system-specific quantum Rice-Ramsperger-Kassel theory calibrated by variational transition-state theory for pressure effects on the addition reaction. The latter is a very convenient way to include variational effects, corner-cutting tunneling, and anharmonicity in falloff calculations. Our results are in very good agreement with the limited experimental data and show the importance of including pressure effects in the temperature interval where the mechanism changes from addition to abstraction. We found a negative temperature effect of the total reaction rate constants at 1 atm pressure in the temperature region where experimental data are missing and accurate theoretical data were previously missing as well. We also calculated the H + C 6 H 6 /C 6 D 6 and D + C 6 H 6 /C 6 D 6 kinetic isotope effects, and we compared our H + C 6 H 6 results to previous theoretical data for H + toluene. We report a very novel nonmonotonic dependence of the kinetic isotope effect on temperature. A particularly striking effect is the prediction of a negative temperature dependence of the total rate constant over 300-500 K wide temperature ranges, depending on the pressure but generally in the range from 600 to 1700 K, which includes the temperature range of ignition in gasoline engines, which is important because aromatics are important components of common fuels.

  20. Direct measurements of the total rate constant of the reaction NCN + H and implications for the product branching ratio and the enthalpy of formation of NCN.

    Science.gov (United States)

    Fassheber, Nancy; Dammeier, Johannes; Friedrichs, Gernot

    2014-06-21

    The overall rate constant of the reaction (2), NCN + H, which plays a key role in prompt-NO formation in flames, has been directly measured at temperatures 962 K rate constants are best represented by the combination of two Arrhenius expressions, k2/(cm(3) mol(-1) s(-1)) = 3.49 × 10(14) exp(-33.3 kJ mol(-1)/RT) + 1.07 × 10(13) exp(+10.0 kJ mol(-1)/RT), with a small uncertainty of ±20% at T = 1600 K and ±30% at the upper and lower experimental temperature limits.The two Arrhenius terms basically can be attributed to the contributions of reaction channel (2a) yielding CH + N2 and channel (2b) yielding HCN + N as the products. A more refined analysis taking into account experimental and theoretical literature data provided a consistent rate constant set for k2a, its reverse reaction k1a (CH + N2 → NCN + H), k2b as well as a value for the controversial enthalpy of formation of NCN, ΔfH = 450 kJ mol(-1). The analysis verifies the expected strong temperature dependence of the branching fraction ϕ = k2b/k2 with reaction channel (2b) dominating at the experimental high-temperature limit. In contrast, reaction (2a) dominates at the low-temperature limit with a possible minor contribution of the HNCN forming recombination channel (2d) at T < 1150 K.

  1. Time-Dependent Quantum Wave Packet Study of the Si + OH → SiO + H Reaction: Cross Sections and Rate Constants.

    Science.gov (United States)

    Rivero Santamaría, Alejandro; Dayou, Fabrice; Rubayo-Soneira, Jesus; Monnerville, Maurice

    2017-03-02

    The dynamics of the Si( 3 P) + OH(X 2 Π) → SiO(X 1 Σ + ) + H( 2 S) reaction is investigated by means of the time-dependent wave packet (TDWP) approach using an ab initio potential energy surface recently developed by Dayou et al. ( J. Chem. Phys. 2013 , 139 , 204305 ) for the ground X 2 A' electronic state. Total reaction probabilities have been calculated for the first 15 rotational states j = 0-14 of OH(v=0,j) at a total angular momentum J = 0 up to a collision energy of 1 eV. Integral cross sections and state-selected rate constants for the temperature range 10-500 K were obtained within the J-shifting approximation. The reaction probabilities display highly oscillatory structures indicating the contribution of long-lived quasibound states supported by the deep SiOH/HSiO wells. The cross sections behave with collision energies as expected for a barrierless reaction and are slightly sensitive to the initial rotational excitation of OH. The thermal rate constants show a marked temperature dependence below 200 K with a maximum value around 15 K. The TDWP results globally agree with the results of earlier quasi-classical trajectory (QCT) calculations carried out by Rivero-Santamaria et al. ( Chem. Phys. Lett. 2014 , 610-611 , 335 - 340 ) with the same potential energy surface. In particular, the thermal rate constants display a similar temperature dependence, with TDWP values smaller than the QCT ones over the whole temperature range.

  2. Influence of pH and ionic strength on electrostatic properties of ferredoxin, FNR, and hydrogenase and the rate constants of their interaction

    Science.gov (United States)

    Diakonova, A. N.; Khrushchev, S. S.; Kovalenko, I. B.; Riznichenko, G. Yu; Rubin, A. B.

    2016-10-01

    Ferredoxin (Fd) protein transfers electrons from photosystem I (PSI) to ferredoxin:NADP+-reductase (FNR) in the photosynthetic electron transport chain, as well as other metabolic pathways. In some photosynthetic organisms including cyanobacteria and green unicellular algae under anaerobic conditions Fd transfers electrons not only to FNR but also to hydrogenase—an enzyme which catalyzes reduction of atomic hydrogen to H2. One of the questions posed by this competitive relationship between proteins is which characteristics of thylakoid stroma media allow switching of the electron flow between the linear path PSI-Fd-FNR-NADP+ and the path PSI-Fd-hydrogenase-H2. The study was conducted using direct multiparticle simulation approach. In this method protein molecules are considered as individual objects that experience Brownian motion and electrostatic interaction with the surrounding media and each other. Using the model we studied the effects of pH and ionic strength (I) upon complex formation between ferredoxin and FNR and ferredoxin and hydrogenase. We showed that the rate constant of Fd-FNR complex formation is constant in a wide range of physiologically significant pH values. Therefore it can be argued that regulation of FNR activity doesn’t involve pH changes in stroma. On the other hand, in the model rate constant of Fd-hydrogenase interaction dramatically depends upon pH: in the range 7-9 it increases threefold. It may seem that because hydrogenase reduces protons it should be more active when pH is acidic. Apparently, regulation of hydrogenase’s affinity to both her reaction partners (H+ and Fd) is carried out by changes in its electrostatic properties. In the dark, the protein is inactive and in the light it is activated and starts to interact with both Fd and H+. Therefore, we can conclude that in chloroplasts the rate of hydrogen production is regulated by pH through the changes in the affinity between hydrogenase and ferredoxin.

  3. Rates and equilibrium constants of the ligand-induced conformational transition of an HCN ion channel protein domain determined by DEER spectroscopy.

    Science.gov (United States)

    Collauto, Alberto; DeBerg, Hannah A; Kaufmann, Royi; Zagotta, William N; Stoll, Stefan; Goldfarb, Daniella

    2017-06-14

    Ligand binding can induce significant conformational changes in proteins. The mechanism of this process couples equilibria associated with the ligand binding event and the conformational change. Here we show that by combining the application of W-band double electron-electron resonance (DEER) spectroscopy with microfluidic rapid freeze quench (μRFQ) it is possible to resolve these processes and obtain both equilibrium constants and reaction rates. We studied the conformational transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP). Using model-based global analysis, the time-resolved data of the μRFQ DEER experiments directly provide fractional populations of the open and closed conformations as a function of time. We modeled the ligand-induced conformational change in the protein using a four-state model: apo/open (AO), apo/closed (AC), bound/open (BO), bound/closed (BC). These species interconvert according to AC + L ⇌ AO + L ⇌ BO ⇌ BC. By analyzing the concentration dependence of the relative contributions of the closed and open conformations at equilibrium, we estimated the equilibrium constants for the two conformational equilibria and the open-state ligand dissociation constant. Analysis of the time-resolved μRFQ DEER data gave estimates for the intrinsic rates of ligand binding and unbinding as well as the rates of the conformational change. This demonstrates that DEER can quantitatively resolve both the thermodynamics and the kinetics of ligand binding and the associated conformational change.

  4. Virtual Instrument for Determining Rate Constant of Second-Order Reaction by pX Based on LabVIEW 8.0.

    Science.gov (United States)

    Meng, Hu; Li, Jiang-Yuan; Tang, Yong-Huai

    2009-01-01

    The virtual instrument system based on LabVIEW 8.0 for ion analyzer which can measure and analyze ion concentrations in solution is developed and comprises homemade conditioning circuit, data acquiring board, and computer. It can calibrate slope, temperature, and positioning automatically. When applied to determine the reaction rate constant by pX, it achieved live acquiring, real-time displaying, automatical processing of testing data, generating the report of results; and other functions. This method simplifies the experimental operation greatly, avoids complicated procedures of manual processing data and personal error, and improves veracity and repeatability of the experiment results.

  5. Beyond transition state theory: accurate description of nuclear quantum effects on the rate and equilibrium constants of chemical reactions using Feynman path integrals.

    Science.gov (United States)

    Vanícek, Jirí

    2011-01-01

    Nuclear tunneling and other nuclear quantum effects have been shown to play a significant role in molecules as large as enzymes even at physiological temperatures. I discuss how these quantum phenomena can be accounted for rigorously using Feynman path integrals in calculations of the equilibrium and kinetic isotope effects as well as of the temperature dependence of the rate constant. Because these calculations are extremely computationally demanding, special attention is devoted to increasing the computational efficiency by orders of magnitude by employing efficient path integral estimators.

  6. Virtual Instrument for Determining Rate Constant of Second-Order Reaction by pX Based on LabVIEW 8.0

    Science.gov (United States)

    Meng, Hu; Li, Jiang-Yuan; Tang, Yong-Huai

    2009-01-01

    The virtual instrument system based on LabVIEW 8.0 for ion analyzer which can measure and analyze ion concentrations in solution is developed and comprises homemade conditioning circuit, data acquiring board, and computer. It can calibrate slope, temperature, and positioning automatically. When applied to determine the reaction rate constant by pX, it achieved live acquiring, real-time displaying, automatical processing of testing data, generating the report of results; and other functions. This method simplifies the experimental operation greatly, avoids complicated procedures of manual processing data and personal error, and improves veracity and repeatability of the experiment results. PMID:19730752

  7. Site-Specific Rate Constant Measurements for Primary and Secondary H- and D-Abstraction by OH Radicals: Propane and n -Butane

    KAUST Repository

    Badra, Jihad

    2014-07-03

    Site-specific rate constants for hydrogen (H) and deuterium (D) abstraction by hydroxyl (OH) radicals were determined experimentally by monitoring the reaction of OH with two normal and six deuterated alkanes. The studied alkanes include propane (C3H8), propane 2,2 D2 (CH 3CD2CH3), propane 1,1,1-3,3,3 D6 (CD 3CH2CD3), propane D8 (C3D 8), n-butane (n-C4H10), butane 2,2-3,3 D4 (CH3CD2CD2CH3), butane 1,1,1-4,4,4 D6 (CD3CH2CH2CD3), and butane D10 (C4D10). Rate constant measurements were carried out over 840-1470 K and 1.2-2.1 atm using a shock tube and OH laser absorption. Previous low-temperature data were combined with the current high-temperature measurements to generate three-parameter fits which were then used to determine the site-specific rate constants. Two primary (P1,H and P 1,D) and four secondary (S00,H, S00,D, S 01,H, and S01,D) H- and D-abstraction rate constants, in which the subscripts refer to the number of C atoms connected to the next-nearest-neighbor C atom, are obtained. The modified Arrhenius expressions for the six site-specific abstractions by OH radicals are P1,H = 1.90 × 10-18T2.00 exp(-340.87 K/T) cm 3molecule-1s-1 (210-1294 K); P1,D= 2.72 × 10-17 T1.60 exp(-895.57 K/T) cm 3molecule-1s-1 (295-1317 K); S00,H = 4.40 × 10-18 T1.93 exp(121.50 K/T) cm 3molecule-1s-1 (210-1294 K); S00,D = 1.45 × 10-20 T2.69 exp(282.36 K/T) cm 3molecule-1s-1 (295-1341 K); S01,H = 4.65 × 10-17 T1.60 exp(-236.98 K/T) cm 3molecule-1s-1 (235-1407 K); S01,D = 1.26 × 10-18 T2.07 exp(-77.00 K/T) cm 3molecule-1s-1 (294-1412 K). © 2014 American Chemical Society.

  8. Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Han, Kun; Jia, Ning; Li, Ji; Yang, Li; Min, Lian-Qiu

    2013-09-01

    The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process.

  9. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  11. Rate constants for the thermal decomposition of ethanol and its bimolecular reactions with OH and D : reflected shock tube and theoretical studies.

    Energy Technology Data Exchange (ETDEWEB)

    Sivaramakrishnan, R.; Su, M.-C.; Michael, J. V.; Klippenstein, S. J.; Harding, L. B.; Ruscic, B. (Chemical Sciences and Engineering Division)

    2010-09-09

    The thermal decomposition of ethanol and its reactions with OH and D have been studied with both shock tube experiments and ab initio transition state theory-based master equation calculations. Dissociation rate constants for ethanol have been measured at high T in reflected shock waves using OH optical absorption and high-sensitivity H-atom ARAS detection. The three dissociation processes that are dominant at high T are: C{sub 2}H{sub 5}OH {yields} C{sub 2}H{sub 4} + H{sub 2}O; C{sub 2}H{sub 5}OH {yields} CH{sub 3} + CH{sub 2}OH; C{sub 2}H{sub 5}OH {yields} C{sub 2}H{sub 5} + OH. The rate coefficient for reaction C was measured directly with high sensitivity at 308 nm using a multipass optical White cell. Meanwhile, H-atom ARAS measurements yield the overall rate coefficient and that for the sum of reactions B and C, since H-atoms are instantaneously formed from the decompositions of CH{sub 2}OH and C{sub 2}H{sub 5} into CH{sub 2}O + H and C{sub 2}H{sub 4} + H, respectively. By difference, rate constants for reaction 1 could be obtained. One potential complication is the scavenging of OH by unreacted ethanol in the OH experiments, and therefore, rate constants for OH + C{sub 2}H{sub 5}OH {yields} products were measured using tert-butyl hydroperoxide (tBH) as the thermal source for OH. The present experiments can be represented by the Arrhenius expression k = (2.5 {+-} 0.43) x 10{sup -11} exp(- 911 {+-} 191 K/T) cm{sup 3} molecule{sup -1} s{sup -1} over the T range 857-1297 K. For completeness, we have also measured the rate coefficient for the reaction of D atoms with ethanol D + C{sub 2}H{sub 5}OH {yields} products whose H analogue is another key reaction in the combustion of ethanol. Over the T range 1054-1359 K, the rate constants from the present experiments can be represented by the Arrhenius expression, k = (3.98 {+-} 0.76) x 10{sup -10} exp(- 4494 {+-} 235 K/T) cm{sup 3} molecule{sup -1} s{sup -1}. The high-pressure rate coefficients for reactions B and C

  12. Calculated rate constants of the chemical reactions involving the main byproducts SO2F, SOF2, SO2F2 of SF6 decomposition in power equipment

    Science.gov (United States)

    Fu, Yuwei; Rong, Mingzhe; Yang, Kang; Yang, Aijun; Wang, Xiaohua; Gao, Qingqing; Liu, Dingxin; Murphy, Anthony B.

    2016-04-01

    SF6 is widely used in electrical equipment as an insulating gas. In the presence of an electric arc, partial discharge (PD) or spark, SF6 dissociation products (such as SF2, SF3 and SF4) react with the unavoidable gas impurities (such as water vapor and oxygen), electrodes and surrounding solid insulation materials, forming several toxic and corrosive byproducts. The main stable decomposition products are SO2F, SO2F2 and SOF2, which have been confirmed experimentally to have a direct relationship with discharge faults, and are thus expected to be useful in the fault diagnosis of power equipment. Various studies have been performed of the main SF6 decomposition species and their concentrations under different types of faults. However, most of the experiments focused on the qualitative analysis of the relationship between the stable products and discharge faults. Although some theoretical research on the formation of main SF6 derivatives have been carried out using chemical kinetics models, the basic data (chemical reactions and their rate constants) adopted in the model are inaccurate and incomplete. The complex chemical reactions of SF6 with the impurities are ignored in most cases. The rate constants of some reactions obtained at ambient temperature or in a narrow temperature range are adopted in the models over a far greater range, for example up to 12 000 K, due to the difficulty in the experimental measurement and theoretical estimation of rate coefficients, particularly at high temperatures. Therefore, improved theoretical models require not only the consideration of additional SF6 decomposition reactions in the presence of impurities but also on improved values of rate constants. This paper is devoted to determining the rate constants of the chemical reactions relating to the main byproducts of SF6 decomposition in SF6 gas-insulated power equipment: SO2F, SOF2 and SO2F2. Quantum chemistry calculations with density functional theory, conventional

  13. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  14. MATHEMATICAL CONSTANTS.

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, H.P.; Potter, Elinor

    1971-03-01

    This collection of mathematical data consists of two tables of decimal constants arranged according to size rather than function, a third table of integers from 1 to 1000, giving some of their properties, and a fourth table listing some infinite series arranged according to increasing size of the coefficients of the terms. The decimal values of Tables I and II are given to 20 D.

  15. Quantum mechanical calculations of state-to-state cross sections and rate constants for the F + DCl → Cl + DF reaction.

    Science.gov (United States)

    Bulut, Niyazi; Kłos, Jacek; Roncero, Octavio

    2015-06-07

    We present accurate state-to-state quantum wave packet calculations of integral cross sections and rate constants for the title reaction. Calculations are carried out on the best available ground 1(2)A' global adiabatic potential energy surface of Deskevich et al. [J. Chem. Phys. 124, 224303 (2006)]. Converged state-to-state reaction cross sections have been calculated for collision energies up to 0.5 eV and different initial rotational and vibrational excitations, DCl(v = 0, j = 0 - 1; v = 1, j = 0). Also, initial-state resolved rate constants of the title reaction have been calculated in a temperature range of 100-400 K. It is found that the initial rotational excitation of the DCl molecule does not enhance reactivity, in contract to the reaction with the isotopologue HCl in which initial rotational excitation produces an important enhancement. These differences between the isotopologue reactions are analyzed in detail and attributed to the presence of resonances for HCl(v = 0, j), absent in the case of DCl(v = 0, j). For vibrational excited DCl(v = 1, j), however, the reaction cross section increases noticeably, what is also explained by another resonance.

  16. Thermal rate constants for the O(3P) + HBr and O(3P) + DBr reactions: transition-state theory and quantum mechanical calculations.

    Science.gov (United States)

    de Oliveira-Filho, Antonio G S; Ornellas, Fernando R; Peterson, Kirk A; Mielke, Steven L

    2013-12-05

    The O((3)P) + HBr → OH + Br and O((3)P) + DBr → OD + Br reactions are studied on a recent high-quality ab initio-based potential energy surface. Thermal rate constants over the 200-1000 K temperature range, calculated using variational transition-state theory (VTST) with the small-curvature tunneling (SCT) correction and quantum mechanical methods with the J-shifting approximation (QM/JS) for zero total angular momentum (J = 0), are reported. These results are compared to the available experimental data, which lie in the ranges of 221-554 and 295-419 K for O + HBr and O + DBr, respectively. The rate constants, in cm(3) molecule(-1) s(-1) and at 298 K, for the O + HBr reaction are 3.66 × 10(-14) for VTST, 3.80 × 10(-14) for QM/JS, and 3.66 × 10(-14) for the average of eight experimental measurements.

  17. Effects of maintenance of propofol-ketamine anesthesia with repeat bolus and constant rate infusion of propofol on physiological, biochemical, anesthetic and analgesic indices in dogs

    Directory of Open Access Journals (Sweden)

    Njoku Uchechukwu Njoku

    2015-12-01

    Full Text Available The research work was aimed at investigating physiological, biochemical, analgesic and anesthetic indices of dogs anesthetized with propofol-ketamine and maintained with repeat bolus and constant infusions of propofol. Eight dogs, assigned to two groups (n=4, were used in this study. All dogs were pre-medicated with atropine (at 0.03 mg/kg bwt and xylazine (at 2 mg/kg bwt. Anesthesia was induced by a concurrent administration of propofol (at 4 mg/kg bwt and ketamine (at 2.5 mg/kg bwt. Maintenance of anesthesia in Group 1 was done with a repeat bolus of propofol (at 2 mg/kg bwt, while in Group 2 it was done with a constant infusion of propofol (at 0.2 mg/kg bwt/min. Gastrotomy was performed in both groups, and anesthesia was maintained for 60 min. Physiological, analgesic, anesthetic parameters and plasma glucose concentration were measured. There was no significant (P>0.05 difference found in the analgesia and pedal reflex scores, durations of analgesia and recumbency, recovery time and standing time between the groups. The heart rate, respiratory rate and rectal temperature reduced significantly (P0.05 between the groups. In conclusion, both maintenance protocols are suitable for dogs, although the repeat bolus technique produces marked cardiopulmonary depression.

  18. Mechanism and Kinetics of Methane Combustion, Part I: Thermal Rate Constants for Hydrogen-Abstraction Reaction of CH4 + O(3P).

    Science.gov (United States)

    Peng, Ya; Jiang, Zhong'an; Chen, Jushi

    2017-03-23

    The mechanism and kinetics of gas-phase hydrogen-abstraction by the O(3P) from methane are investigated using ab initio calculations and dynamical methods. Not only are the electronic structure properties including the optimized geometries, relative energies, and vibrational frequencies of all the stationary points obtained from state-averaged complete active space self-consistent field calculations, but also the single-point energies for all points on the intrinsic reaction coordinate are evaluated using the internally contracted multireference configuration interaction approach with modified optimized cc-pCVDZ basis sets. Our calculations give a fairly accurate description of the regions around the 3A″ transition state in the O(3P) attacking a near-collinear H-CH3 direction with a barrier height of 12.53 kcal/mol, which is lower than those reported before. Subsequently, thermal rate constants for this hydrogen-abstraction are calculated using the canonical unified statistical theory method with the temperature ranging from 298 K to 1000 K. These calculated rate constants are in agreement with experiments. The present work reveals the reaction mechanism of hydrogen-abstraction by the O(3P) from methane, and it is helpful for the understanding of methane combustion.

  19. On the Theory of Oxidation-Reduction Reactions Involving Electron Transfer. V. Comparison and Properties of Electrochemical and Chemical Rate Constants

    Science.gov (United States)

    Marcus, R. A.

    1962-01-01

    Using a theory of electron transfers which takes cognizance of reorganization of the medium outside the inner coordination shell and of changes of bond lengths inside it, relations between electrochemical and related chemical rate constants are deduced and compared with the experimental data. A correlation is found, without the use of arbitrary parameters. Effects of weak complexes with added electrolytes are included under specified conditions. The deductions offer a way of coordinating a variety of data in the two fields, internally as well as with each those in another. For example, the rate of oxidation or reduction of a series of related reactants by one reagent is correlated with that of another and with that of the corresponding electrochemical oxidation-reduction reaction, under certain specified conditions. These correlations may also provide a test for distinguishing an electron from an atom transfer mechanism. (auth)

  20. A quantum method for thermal rate constant calculations from stationary phase approximation of the thermal flux-flux correlation function integral.

    Science.gov (United States)

    Aieta, Chiara; Ceotto, Michele

    2017-06-07

    This paper presents a quantum mechanical approximation to the calculation of thermal rate constants. The rate is derived from a suitable stationary phase approximation to the time integral of the thermal flux-flux correlation function. The goal is to obtain an expression that barely depends on the position of the flux operators, i.e., of the dividing surfaces, so that it can be applied also to complex systems by arbitrarily locating the dividing surfaces. The approach is tested on one and two dimensional systems where quantum effects are predominant over a wide range of temperatures. The results are quite accurate, i.e., within a few percent of the exact values for a reasonable range of dividing surface positions.

  1. Rate constant for the reaction of OH with CH3CCl2F (HCFC-141b) determined by relative rate measurements with CH4 and CH3CCl3

    Science.gov (United States)

    Huder, Karin; Demore, William B.

    1993-01-01

    Determination of accurate rate constants for OH abstraction is of great importance for the calculation of lifetimes for HCFCs and their impact on the atmosphere. For HCFC-141b there has been some disagreement in the literature for absolute measurements of this rate constant. In the present work rate constant ratios for HCFC-141b were measured at atmospheric pressure in the temperature range of 298-358 K, with CH4 and CH3CCl3 as reference gases. Ozone was photolyzed at 254 nm in the presence of water vapor to produce OH radicals. Relative depletions of 141b and the reference gases were measured by FTIR. Arrhenius expressions for 141b were derived from each reference gas and found to be in good agreement with each other. The combined expression for HCFC-141b which we recommend is 1.4 x 10 exp -12 exp(-1630/T) with k at 298 K being 5.9 x 10 exp -15 cu cm/molec-s. This value is in excellent agreement with the JPL 92-20 recommendation.

  2. The reaction O((3)P) + HOBr: Temperature dependence of the rate constant and importance of the reaction as an HOBr stratospheric loss process

    Science.gov (United States)

    Nesbitt, F. L.; Monks, P. S.; Payne, W. A.; Stief, L. J.; Toumi, R.

    1995-01-01

    The absolute rate constant for the reaction O((3)P) + HOBr has been measured between T = 233K and 423K using the discharge-flow kinetic technique coupled to mass spectrometric detection. The value of the rate coefficient at room temperature is (2.5 +/- 0.6) x 10(exp -11)cu cm/molecule/s and the derived Arrhenius expression is (1.4 +/- 0.5) x 10(exp -10) exp((-430 +/- 260)/T)cu cm/molecule/s. From these rate data the atmospheric lifetime of HOBr with respect to reaction with O((3)P) is about 0.6h at z = 25 km which is comparable to the photolysis lifetime based on recent measurements of the UV cross section for HOBr. Implications for HOBr loss in the stratosphere have been tested using a 1D photochemical box model. With the inclusion of the rate parameters and products for the O + HOBr reaction, calculated concentration profiles of BrO increase by up to 33% around z = 35 km. This result indicates that the inclusion of the O + HOBr reaction in global atmospheric chemistry models may have an impact on bromine partitioning in the middle atmosphere.

  3. Modeling the downward transport of {sup 210}Pb in Peatlands: Initial Penetration‐Constant Rate of Supply (IP-CRS) model

    Energy Technology Data Exchange (ETDEWEB)

    Olid, Carolina, E-mail: olid.carolina@gmail.com [Department of Ecology and Environmental Science, Umeå University, SE-90187, Umeå (Sweden); Diego, David [Department of Earth Science, University of Bergen, NO-5020 Bergen (Norway); Garcia-Orellana, Jordi [Departament de Física, Universitat Autònoma de Barcelona, E-08193 Bellaterra (Spain); Institut de Ciència i Tecnologia Ambientals (ICTA), Universitat Autònoma de Barcelona, E-08193 Bellaterra (Spain); Cortizas, Antonio Martínez [Departamento de Edafoloxía e Química Agrícola, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Klaminder, Jonatan [Department of Ecology and Environmental Science, Umeå University, SE-90187, Umeå (Sweden)

    2016-01-15

    The vertical distribution of {sup 210}Pb is commonly used to date peat deposits accumulated over the last 100–150 years. However, several studies have questioned this method because of an apparent post-depositional mobility of {sup 210}Pb within some peat profiles. In this study, we introduce the Initial Penetration–Constant Rate of Supply (IP-CRS) model for calculating ages derived from {sup 210}Pb profiles that are altered by an initial migration of the radionuclide. This new, two-phased, model describes the distribution of atmospheric-derived {sup 210}Pb ({sup 210}Pb{sub xs}) in peat taking into account both incorporation of {sup 210}Pb into the accumulating peat matrix as well as an initial flushing of {sup 210}Pb through the uppermost peat layers. The validity of the IP-CRS model is tested in four anomalous {sup 210}Pb peat records that showed some deviations from the typical exponential decay profile not explained by variations in peat accumulation rates. Unlike the most commonly used {sup 210}Pb-dating model (Constant Rate of Supply (CRS)), the IP-CRS model estimates peat accumulation rates consistent with typical growth rates for peatlands from the same areas. Confidence in the IP-CRS chronology is also provided by the good agreement with independent chronological markers (i.e. {sup 241}Am and {sup 137}Cs). Our results showed that the IP-CRS can provide chronologies from peat records where {sup 210}Pb mobility is evident, being a valuable tool for studies reconstructing past environmental changes using peat archives during the Anthropocene. - Highlights: • Accurate age dating of peat and sediment cores is critical for evaluating change. • A new {sup 210}Pb dating model that includes vertical transport of {sup 210}Pb was developed. • The IP-CRS model provided consistent peat accumulation rates. • The IP-CRS ages were consistent with independent chronological markers. • The IP-CRS model derives peat ages where downward {sup 210}Pb transport is

  4. Ab initio study of the HO2+NO reaction: Prediction of the total rate constant and product branching ratios for the forward and reverse processes

    Science.gov (United States)

    Zhu, R. S.; Lin, M. C.

    2003-11-01

    The mechanisms for HO2+NO and its reverse reactions have been investigated by ab initio molecular orbital and transition-state theory calculations. The species involved have been optimized at the B3LYP/6-311+G(3df,2p) level and their energies refined by single-point calculations with the highest scheme of the modified Gaussian-2 method. Ab initio results show that formation of HO+NO2 from HO2+NO by the direct fragmentation of the peroxynitrous acid, HOONO intermediate, is predominant; the alternative path occurring by the isomerization of HOONO to HONO2 is 5.2 kcal/mol less favorable. The stepwise formation of HNO+O2 from HOONO is energetically unfavorable; the barriers for the direct H abstract reactions via singlet and triplet paths are found to be rather high also. Rate constant calculations show that the forward reaction is pressure independent below 10 atm; the reverse OH+NO2 reactions producing HONO2 and HOONO appear to be strongly pressure dependent; below 1 atm, the yield of HOONO from HO+NO2 is <2.5% at 300-400 K, it reaches 12.2% and 9.1%, respectively, at 300 and 400 K at 3.8×104 Torr pressure. The low- and high-pressure rate constants with He as a third-body for the formation of HOONO and HONO2 from the HO+NO2 reaction can be expressed by k0 (HOONO)=3.15×102 T-12.3 exp(-585/T), k0 (HONO2)=3.32×10-6 T-8.8 exp(-1569/T)cm6 molecule-2 s-1 and k∞ (HOONO)=1.71×10-10 T-0.24 exp(100/T) and k∞ (HONO2)=4.74×10-9T-0.82 exp(21/T) cm3 molecule-1 s-1, respectively, in the temperature range of 200-2000 K. The unimolecular decomposition rate constant (in Ar) of HNO3 can be expressed as kd∞ (HNO3)=2.30×1023T-2.27 exp(-26317/T) s-1 and kd0 (HNO3)=1.27×1015 T-6.55exp(-26038/T) cm3 molecule-1 s-1, respectively. The predicted values are all in close agreement with experimental data for both forward and reverse processes.

  5. Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer’s drug candidates

    Directory of Open Access Journals (Sweden)

    Gao Y

    2015-02-01

    Full Text Available Ya Gao,1,* Ya-zhuo Hu,1,* Rui-sheng Li,2 Zhi-tao Han,1 Yan Geng,1 Zheng Xia,1 Wen-jin Du,3 Li-xin Liu,4 Hong-hong Zhang,1 Lu-ning Wang5 1Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, 2Research and Technology Service Center, PLA 302 Hospital, 3Department of Neurology, Air Force General Hospital, 4Department of Neurology, Beijing Geriatric Hospital, 5Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work and are joint first authors Background: Cattle encephalon glycoside and ignotin injection (CEGI, a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People’s Republic of China. However, data regarding the effect of CEGI on Alzheimer’s disease (AD remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1+ activated microglia

  6. Rate constant for the reaction of OH with methyl iodide, a re-determination by flash photolysis of water vapour and time resolved resonance fluorescence of OH

    Science.gov (United States)

    Zhang, Shaoliang; Strekowski, Rafal; Zetzsch, Cornelius

    2010-05-01

    Methyl iodide is a major source gas for atmospheric iodine, and it is mainly emitted from the ocean. Aqueous-phase reactions, such as hydrolysis and exchange reactions with chloride control its emissions to the atmosphere, where its lifetime is limited to less than a week, mainly by photolysis. A minor contribution to the loss processes in the troposphere is the gas-phase reaction with OH radicals, that has been investigated by several authors. On the other hand, this reaction turned out to be uncertain in spite of interest in nuclear safety after the International Phebus Fission Product programme, initiated in 1988. Some of the most important observed phenomena with regard to the chemistry of iodine were not predicted, clearly showing the need for carrying out rate constant determinations for the reactions of I2 and CH3I with OH, which is a major oxidant product from the air radiolysis under accident conditions. We have measured the rate constant for the reaction OH + CH3I - H2O + CH2I in He at 260 mbar in the temperature range from 298 to 362 K. OH radicals were produced by flash photolysis of H2O in the vacuum-UV at wavelengths > 115 nm using a Xe flash lamp with a MgF2 window. Time profiles of OH radicals are monitored by resonance fluorescence of the A2 Σ - X2 Π transition at 308 nm, induced by the emission from a microwave discharge of a flow of He and H2O, a few Torr each. The signal is monitored by photon counting and multichannel scaling, collecting the counts from 50 flashes each, obtaind by pulsed photolysis of various mixtures of H2O and CH3I under slow-flow conditions. Decays of OH in the presence of CH3I are observed to be exponential, and the decay rates are found to be linearly dependent on the concentration of CH3I. Rate constants, k ± 2σ (in units of 10-14 cm3 s-1) of 4.14±0.20, 6.33±0.68, 7.31±1.18 and 8.24±1.60 at 298, 326, 352 and 362 K, respectively, are obtained from linear regressions and lead to an Arrhenius expression of k = 1.5

  7. Standard Glbbs Energy of Formation of the Hydroxyl Radical in Aqueous Solution. Rate Constants for the Reaction C102- -t O3 S 03- -t CIO,

    DEFF Research Database (Denmark)

    Klaning, U. K.; Sehested, Knud; Holcman, J.

    1985-01-01

    Eoa,(OH/OH-) were determined by means of kf and k,, the equilibrium constant of 03- + O2 + 0-, the pK of the hydroxyl radical, A&Oa, of 030, 2a,n d OH-i n aqueous solution, and E0,,(C1O2/C1O2-) = 0.934 V determined in the present work. Apoa,(OH) = 26.8 * 1 kJ mol-' and Eoao(OH/OH-) = 1.91 * 0.01 V......The rate constants of the following reactions were determined by pulse radiolysis and stopped-flow experiments: C102- + O3 + C102 + 03-(k f= (4 f 1) X lo6 dm3 mol-' s-', k, = (1.8 f 0.2) X lo5 dm3 mol-' s-]); C102 + OH - C103- + H+ (k = (4.0 * 0.4) X lo9 dm3 mol-' s-l); C102 + 0- - C103- (k = (2...

  8. Estimation of Slow Crack Growth Parameters for Constant Stress-Rate Test Data of Advanced Ceramics and Glass by the Individual Data and Arithmetic Mean Methods

    Science.gov (United States)

    Choi, Sung R.; Salem, Jonathan A.; Holland, Frederic A.

    1997-01-01

    The two estimation methods, individual data and arithmetic mean methods, were used to determine the slow crack growth (SCG) parameters (n and D) of advanced ceramics and glass from a large number of room- and elevated-temperature constant stress-rate ('dynamic fatigue') test data. For ceramic materials with Weibull modulus greater than 10, the difference in the SCG parameters between the two estimation methods was negligible; whereas, for glass specimens exhibiting Weibull modulus of about 3, the difference was amplified, resulting in a maximum difference of 16 and 13 %, respectively, in n and D. Of the two SCG parameters, the parameter n was more sensitive to the estimation method than the other. The coefficient of variation in n was found to be somewhat greater in the individual data method than in the arithmetic mean method.

  9. Radiosensitization of DNA by Cisplatin Adducts Results from an Increase in the Rate Constant for the Reaction with Hydrated Electrons and Formation of Pt(I).

    Science.gov (United States)

    Behmand, B; Marignier, J-L; Mostafavi, M; Wagner, J R; Hunting, D J; Sanche, L

    2015-07-30

    Pulse radiolysis measurements of the decay of hydrated electrons in solutions containing different concentrations of the oligonucleotide GTG with and without a cisplatin adduct show that the presence of a cisplatin moiety accelerates the reaction between hydrated electrons and the oligonucleotide. The rate constant of the reaction is found to be 2.23 × 10(10) mol(-1) L s(-1), which indicates that it is diffusion controlled. In addition, we show for the first time the formation of a Pt(I) intermediate as a result of the reaction of hydrated electrons with GTG-cisplatin. A putative reaction mechanism is proposed, which may form the basis of the radiosensitization of cancer cells in concomitant chemoradiation therapy with cisplatin.

  10. A systematic evaluation of the dose-rate constant determined by photon spectrometry for 21 different models of low-energy photon-emitting brachytherapy sources.

    Science.gov (United States)

    Chen, Zhe Jay; Nath, Ravinder

    2010-10-21

    The aim of this study was to perform a systematic comparison of the dose-rate constant (Λ) determined by the photon spectrometry technique (PST) with the consensus value ((CON)Λ) recommended by the American Association of Physicists in Medicine (AAPM) for 21 low-energy photon-emitting interstitial brachytherapy sources. A total of 63 interstitial brachytherapy sources (21 different models with 3 sources per model) containing either (125)I (14 models), (103)Pd (6 models) or (131)Cs (1 model) were included in this study. A PST described by Chen and Nath (2007 Med. Phys. 34 1412-30) was used to determine the dose-rate constant ((PST)Λ) for each source model. Source-dependent variations in (PST)Λ were analyzed systematically against the spectral characteristics of the emitted photons and the consensus values recommended by the AAPM brachytherapy subcommittee. The values of (PST)Λ for the encapsulated sources of (103)Pd, (125)I and (131)Cs varied from 0.661 to 0.678 cGyh(-1) U(-1), 0.959 to 1.024 cGyh(-1)U(-1) and 1.066 to 1.073 cGyh(-1)U(-1), respectively. The relative variation in (PST)Λ among the six (103)Pd source models, caused by variations in photon attenuation and in spatial distributions of radioactivity among the source models, was less than 3%. Greater variations in (PST)Λ were observed among the 14 (125)I source models; the maximum relative difference was over 6%. These variations were caused primarily by the presence of silver in some (125)I source models and, to a lesser degree, by the variations in photon attenuation and in spatial distribution of radioactivity among the source models. The presence of silver generates additional fluorescent x-rays with lower photon energies which caused the (PST)Λ value to vary from 0.959 to 1.019 cGyh(-1)U(-1) depending on the amount of silver used by a given source model. For those (125)I sources that contain no silver, their (PST)Λ was less variable and had values within 1% of 1.024 cGyh(-1)U(-1). For the 16

  11. Precise Determination of the Strong Coupling Constant at NNLO in QCD from the Three-Jet Rate in Electron-Positron Annihilation at LEP

    Science.gov (United States)

    Dissertori, G.; Gehrmann-Deridder, A.; Gehrmann, T.; Glover, E. W. N.; Heinrich, G.; Stenzel, H.

    2010-02-01

    We present the first determination of the strong coupling constant from the three-jet rate in e+e- annihilation at LEP, based on a next-to-next-to-leading-order (NNLO) perturbative QCD prediction. More precisely, we extract αs(MZ) by fitting perturbative QCD predictions at O(αs3) to data from the ALEPH experiment at LEP. Over a large range of the jet-resolution parameter ycut, this observable is characterized by small nonperturbative corrections and an excellent stability under renormalization scale variation. We find αs(MZ)=0.1175±0.0020(expt)±0.0015(theor), which is more accurate than the values of αs(MZ) from e+e- event-shape data currently used in the world average.

  12. The rate constant of the reaction NCN + H2 and its role in NCN and NO modeling in low pressure CH4/O2/N2-flames.

    Science.gov (United States)

    Faßheber, Nancy; Lamoureux, Nathalie; Friedrichs, Gernot

    2015-06-28

    Bimolecular reactions of the NCN radical play a key role in modeling prompt-NO formation in hydrocarbon flames. The rate constant of the so-far neglected reaction NCN + H2 has been experimentally determined behind shock waves under pseudo-first order conditions with H2 as the excess component. NCN3 thermal decomposition has been used as a quantitative high temperature source of NCN radicals, which have been sensitively detected by difference UV laser absorption spectroscopy at [small nu, Greek, tilde] = 30383.11 cm(-1). The experiments were performed at two different total densities of ρ≈ 4.1 × 10(-6) mol cm(-3) and ρ≈ 7.4 × 10(-6) mol cm(-3) (corresponding to pressures between p = 324 mbar and p = 1665 mbar) and revealed a pressure independent reaction. In the temperature range 1057 K rate constant can be represented by the Arrhenius expression k/(cm(3) mol(-1) s(-1)) = 4.1 × 10(13) exp(-101 kJ mol(-1)/RT) (Δlog k = ±0.11). The pressure independent reaction as well as the measured activation energy is consistent with a dominating H abstracting reaction channel yielding the products HNCN + H. The reaction NCN + H2 has been implemented together with a set of reactions for subsequent HNCN and HNC chemistry into the detailed GDFkin3.0_NCN mechanism for NOx flame modeling. Two fuel-rich low-pressure CH4/O2/N2-flames served as examples to quantify the impact of the additional chemical pathways. Although the overall NCN consumption by H2 remains small, significant differences have been observed for NO yields with the updated mechanism. A detailed flux analysis revealed that HNC, mainly arising from HCN/HNC isomerization, plays a decisive role and enhances NO formation through a new HNC → HNCO → NH2→ NH → NO pathway.

  13. Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on the stress response, urine production, and anesthetic recovery characteristics in horses anesthetized with isoflurane.

    Science.gov (United States)

    Creighton, Catherine M; Lemke, Kip A; Lamont, Leigh A; Horney, Barbara S; Doyle, Aimie J

    2012-04-15

    To compare the effect of xylazine bolus versus medetomidine constant rate infusion (MCRI) on serum cortisol and glucose concentrations, urine production, and anesthetic recovery characteristics in dorsally recumbent, spontaneously breathing, isoflurane-anesthetized horses. Prospective, randomized crossover study. 10 healthy Standardbreds. Horses were premedicated with xylazine or medetomidine IV. Anesthesia was induced with diazepam and ketamine and maintained with isoflurane for 150 minutes. For the xylazine treatment, end-tidal isoflurane concentration was maintained at 1.7% and xylazine (0.2 mg/kg [0.09 mg/lb]), IV) was administered as a bolus at the end of anesthesia. For the MCRI treatment, end-tidal isoflurane concentration was maintained at 1.4% and medetomidine (0.005 mg/kg/h [0.0023 mg/lb/h], IV) was infused throughout anesthesia. Serum cortisol and glucose concentrations were measured before, during, and after anesthesia. Urine specific gravity and volume were measured during anesthesia. Unassisted anesthetic recoveries were recorded by a digital video camera for later evaluation by 2 observers who were blinded to treatment. Serum cortisol concentration was lower and serum glucose concentration was higher with MCRI treatment, compared with xylazine treatment. Time to sternal recumbency was longer with MCRI treatment, but no difference was seen between treatments for times to extubation, first movement, or standing. Objective (mean attempt interval) and subjective (visual analog score) recovery scores were significantly better with MCRI treatment, compared with xylazine treatment. In isoflurane-anesthetized horses, premedication and administration of medetomidine as a constant rate infusion resulted in decreased serum cortisol concentration, increased serum glucose concentration, and superior anesthetic recovery characteristics, compared with conventional treatment with xylazine.

  14. Electron attachment to POCl3: Measurement and theoretical analysis of rate constants and branching ratios as a function of gas pressure and temperature, electron temperature, and electron energy

    Science.gov (United States)

    Van Doren, Jane M.; Friedman, Jeffery F.; Miller, Thomas M.; Viggiano, A. A.; Denifl, S.; Scheier, P.; Märk, T. D.; Troe, J.

    2006-03-01

    Two experimental techniques, electron swarm and electron beam, have been applied to the problem of electron attachment to POCl3, with results indicating that there is a competition between dissociation of the resonant POCl3-* state and collisional stabilization of the parent anion. In the electron beam experiment at zero electron energy, the fragment ion POCl2- is the dominant ion product of attachment (96%), under single-collision conditions. Small amounts (˜2% each) of POCl3- and Cl - were observed. POCl3- and POCl2- ion products were observed only at zero electron energy, but higher-energy resonances were recorded for POCl-, Cl-, and Cl2- ion products. In the electron swarm experiment, which was carried out in 0.4-7Torr of He buffer gas, the parent anion branching ratio increased significantly with pressure and decreased with temperature. The electron attachment rate constant at 297K was measured to be (2.5±0.6)×10-7cm3s-1, with ion products POCl2- (71%) and POCl3- (29%) in 1Torr of He gas. The rate constant decreased as the electron temperature was increased above 1500K. Theory is developed for (a) the unimolecular dissociation of the nascent POCl3-* and (b) a stepladder collisional stabilization mechanism using the average energy transferred per collision as a parameter. These ideas were then used to model the experimental data. The modeling showed that D0o(Cl -POCl2-) and EA(POCl3) must be the same within ±0.03eV.

  15. Tunable Yb-doped fiber laser based on a FBG array and a theta ring resonator ensuring a constant repetition rate (Conference Presentation)

    Science.gov (United States)

    Tiess, Tobias; Becker, Martin; Rothhardt, Manfred; Bartelt, Hartmut; Jäger, Matthias L.

    2017-03-01

    Fiber lasers provide the perfect basis to develop broadly tunable lasers with high efficiency, excellent beam quality and user-friendly operation as they are increasingly demanded by applications in biophotonics and spectroscopy. Recently, a novel tuning scheme has been presented using fiber Bragg grating (FBG) arrays as fiber-integrated spectral filters containing many standard FBGs with different feedback wavelengths. Based on the discrete spectral sampling, these reflective filters uniquely enable tailored tuning ranges and broad bandwidths to be implemented into fiber lasers. Even though the first implementation of FBG arrays in pulsed tunable lasers based on a sigma ring resonators works with good emission properties, the laser wavelength is tuned by a changing repetition rate, which causes problems with applications in synchronized environments. In this work, we present a modified resonator scheme to maintain a constant repetition rate over the tuning range and still benefit from the advantages of FBG arrays as filters. With a theta ring cavity and two counter propagating filter passes, the distributed feedback of the FBG array is compensated resulting in a constant pulse round trip time for each filter wavelength. Together with an adapted gating scheme controlling the emission wavelength with a modulator, the tuning principle has been realized based on a Ytterbium-doped fiber laser. We present first experimental results demonstrating a tuning range of 25nm, high signal contrast and pulse durations of about 10ns. With the prospect of tailored tuning ranges, this pulsed fiber-integrated laser may be the basis to tackle challenging applications in spectroscopy.

  16. Direct determination of rate constants for coupling between aromatic radical anions and alkyl and benzyl radicals by laser-flash photolysis

    DEFF Research Database (Denmark)

    Lund, T.; Christensen, P.; Wilbrandt, Robert Walter

    2003-01-01

    Coupling rates between the radicals methyl, n-, sec-, tert-butyl and benzyl (R-.) and the aromatic radical anions of 1,4-dicyanonaphthalene, 9,10-dicyanoanthracene and fluorenone (A(-.)) have been obtained using a new laser-flash photolysis method. The radicals R-. and the radical anions A(-.) we...... of the radicals and the structure and standard potentials of the aromatic radical anions.......Coupling rates between the radicals methyl, n-, sec-, tert-butyl and benzyl (R-.) and the aromatic radical anions of 1,4-dicyanonaphthalene, 9,10-dicyanoanthracene and fluorenone (A(-.)) have been obtained using a new laser-flash photolysis method. The radicals R-. and the radical anions A(-.) were...... generated by a photoinduced electron transfer reaction between the aromatic compound A and the alkyl or benzyl triphenylborate anion RB(Ph)(3)(-). For the first time the rate constants of the coupling reaction between methyl and benzyl radicals with aromatic radical anions have been obtained. For all...

  17. Examination of Alzheimer’s-related positive, negative and reactive pathology in the brainstem of APPswe/PS1ΔE9 mice

    DEFF Research Database (Denmark)

    Metaxas, Athanasios; Vaitheeswaran, Ramanan; Ilkjær, Laura

    Aim: While the positive, negative and reactive lesions of Alzheimer’s disease (AD) have been extensively characterised in brain areas associated with cognition, such as the cortex and the hippocampus, the status of subcortical structures in AD remains less well characterised. In the present study......, we examined AD-related pathology in the midbrain brainstem of the APPswe/PS1ΔE9 mouse model of amyloidosis (APP/PS1). Methods: For positive lesions, fresh-frozen brainstem sections from female, 12 months old, transgenic and control mice (n=6/genotype) were stained for amyloid beta and tau, using 6E10...... immunohistochemistry and the Gallyas silver stain respectively. Negative lesions were examined by tryptophan hydroxylase (TPH) 2 immunohistochemistry, and by measuring binding and mRNA levels of the serotonin transporter (SERT). Reactive lesions were investigated by Iba1 immunostaining of microglial cells...

  18. Testing for redshift evolution of Type Ia supernovae using the strongly lensed PS1-10afx at z = 1.4

    Science.gov (United States)

    Petrushevska, T.; Amanullah, R.; Bulla, M.; Kromer, M.; Ferretti, R.; Goobar, A.; Papadogiannakis, S.

    2017-07-01

    Context. The light from distant supernovae (SNe ) can be magnified through gravitational lensing when a foreground galaxy is located along the line of sight. This line-up allows for detailed studies of SNe at high redshift that otherwise would not be possible. Spectroscopic observations of lensed high-redshift Type Ia supernovae (SNe Ia) are of particular interest since they can be used to test for evolution of their intrinsic properties. The use of SNe Ia for probing the cosmic expansion history has proven to be an extremely powerful method for measuring cosmological parameters. However, if systematic redshift-dependent properties are found, their usefulness for future surveys could be challenged. Aims: We investigate whether the spectroscopic properties of the strongly lensed and very distant SN Ia PS1-10afx at z = 1.4, deviates from the well-studied populations of normal SNe Ia at nearby or intermediate distance. Methods: We created median spectra from nearby and intermediate-redshift spectroscopically normal SNe Ia from the literature at - 5 and + 1 days from light-curve maximum. We then compared these median spectra to those of PS1-10afx. Results: We do not find signs of spectral evolution in PS1-10afx. The observed deviation between PS1-10afx and the median templates are within what is found for SNe at low and intermediate redshift. There is a noticeable broad feature centred at λ 3500 Å, which is present only to a lesser extent in individual low- and intermediate-redshift SN Ia spectra. From a comparison with a recently developed explosion model, we find this feature to be dominated by iron peak elements, in particular, singly ionized cobalt and chromium.

  19. miR-34a deficiency in APP/PS1 mice promotes cognitive function by increasing synaptic plasticity via AMPA and NMDA receptors.

    Science.gov (United States)

    Xu, Yuelong; Chen, Ping; Wang, Xianjun; Yao, Jinguo; Zhuang, Sujing

    2018-02-06

    MicroRNA (miR)-34a was recently determined to contribute to the pathological development of Alzheimer's disease (AD). miR-34a deficiency significantly attenuates cognitive deficits in amyloid precursor protein (APP)/presenilin 1 (PS1) mice; however, its role in early AD pathology and the underlying mechanisms remain elusive. Here, we confirmed that the increase of miR-34a expression in APP/PS1 mice was earlier than the relevant AD pathological characteristics, such as amyloid-β production, amyloid plaque deposition, and cognitive deficits. Furthermore, because predicted miR-34a target genes were broadly linked to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, we evaluated synaptic plasticity by investigating high-frequency conditioning tetanus-induced excitatory postsynaptic potential, which revealed that synaptic plasticity was promoted in miR-34a knockout/APP/PS1 mice. Therefore, we assessed the expression of the presynaptic components synaptophysin and postsynaptic density protein 95 (PSD95) and found that synaptophysin and PSD95 were not altered by miR-34a deficiency. Additionally, the synaptic strength (vesicular fusion, vesicular docking, and transporting) was either not significantly changed. We also evaluated the levels of AMPA and NMDA receptors, which showed that the expression of AMPA and NMDA receptors was markedly upregulated in APP/PS1 mice with miR-34a deficiency. We conclude that miR-34a is involved in synaptic deficits in AD pathological development, which was, at least in part, due to the inhibition of NMDA (by miR-34a-5p) and AMPA (by miR-34a-3p) receptor expression. Copyright © 2018. Published by Elsevier B.V.

  20. Regional brain metabolism with cytochrome c oxidase histochemistry in a PS1/A246E mouse model of autosomal dominant Alzheimer's disease: correlations with behavior and oxidative stress.

    Science.gov (United States)

    Strazielle, Catherine; Jazi, Rozat; Verdier, Yann; Qian, Sue; Lalonde, Robert

    2009-12-01

    Mitochondrial dysfunction and brain metabolic alteration are early neurofunctional aspects in Alzheimer's disease (AD). Regional brain metabolism was analyzed by cytochrome c oxidase (COX) histochemistry in PS1-A246E mouse mutants, a model of autosomal dominant AD overexpressing beta-amyloid (Abeta) peptide without amyloidosis or cell degeneration. Immunohistochemical samples were analyzed on adjacent sections for regional Abeta1-42 levels, as well as DNA oxidative damage with 8-hydroxy-2-deoxyguanosine (8-OHdG). COX activity increased in the basal forebrain nuclear complex, specific parts of the amygdala and hippocampus, as well as in striatum and connected regions. On the contrary, a hypometabolism was observed in midline thalamic, interpeduncular, and pedonculopontine nuclei. The integration of these regions in circuitries subserving emotions, arousal, and cognitive functions may explain why neurochemical alterations in specific brain regions were linearly correlated with psychomotor slowing and disinhibition previously reported in the mutant. As the PS1-A246E model appears to mimick prodromal AD, the results support the existence of mitochondrial abnormalities prior to AD-related cognitive deficits. However, since affected PS1-A246E brain regions were not primarily those altered in AD-associated histopathological features and did not systematically display either Abeta overexpression or higher 8-OHdG immunolabelling, the hypermetabolism observed seems to comprise a compensatory reaction to early mitochondrial abnormalities; furthermore, neuronal synaptic function should be considered as particularly relevant in COX activity changes.

  1. PS1/γ-Secretase-Mediated Cadherin Cleavage Induces β-Catenin Nuclear Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells

    Science.gov (United States)

    Dias, Rhayra B.; Fortuna-Costa, Anneliese; Chicaybam, Leonardo; Lopes, Daiana V.; Dutra, Hélio S.; Borojevic, Radovan; Bonamino, Martin; Mermelstein, Claudia

    2016-01-01

    Bone marrow stromal cells (BMSCs) are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation of β-catenin signaling, classically known to be regulated by the canonical Wnt pathway. However, BMSCs treatment with canonical Wnts in vitro does not always result in osteogenic differentiation and evidence indicates that a more complex signaling pathway, involving cadherins, would be required to induce β-catenin signaling in these cells. Here we showed that Wnt3a alone did not induce TCF activation in BMSCs, maintaining the cells at a proliferative state. On the other hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins were cleaved by the PS1/γ-secretase complex at the plasma membrane, and this event was associated with an enhanced β-catenin translocation to the nucleus and signaling. When PS1/γ-secretase activity was inhibited, the osteogenic process was impaired. Altogether, we provide evidence that PS1/γ-secretase-mediated cadherin cleavage has as an important role in controlling β-catenin signaling during the onset of BMSCs osteogenic differentiation, as part of a complex signaling pathway responsible for cell fate decision. A comprehensive map of these pathways might contribute to the development of strategies to improve bone repair. PMID:28053606

  2. PS1/γ-Secretase-Mediated Cadherin Cleavage Induces β-Catenin Nuclear Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells

    Directory of Open Access Journals (Sweden)

    Danielle C. Bonfim

    2016-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation of β-catenin signaling, classically known to be regulated by the canonical Wnt pathway. However, BMSCs treatment with canonical Wnts in vitro does not always result in osteogenic differentiation and evidence indicates that a more complex signaling pathway, involving cadherins, would be required to induce β-catenin signaling in these cells. Here we showed that Wnt3a alone did not induce TCF activation in BMSCs, maintaining the cells at a proliferative state. On the other hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins were cleaved by the PS1/γ-secretase complex at the plasma membrane, and this event was associated with an enhanced β-catenin translocation to the nucleus and signaling. When PS1/γ-secretase activity was inhibited, the osteogenic process was impaired. Altogether, we provide evidence that PS1/γ-secretase-mediated cadherin cleavage has as an important role in controlling β-catenin signaling during the onset of BMSCs osteogenic differentiation, as part of a complex signaling pathway responsible for cell fate decision. A comprehensive map of these pathways might contribute to the development of strategies to improve bone repair.

  3. Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice.

    Science.gov (United States)

    Kalifa, Sara; Polston, Eva K; Allard, Joanne S; Manaye, Kebreten F

    2011-02-28

    Cannabinoids have neuroprotective effects that are exerted primarily through cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor distribution in the double transgenic (dtg) APP(swe)/PS1(ΔE9) mouse model for Alzheimer's disease. Immunohistochemical labeling of CB1 protein in non-transgenic mice revealed that CB1 was highly expressed in the hippocampus, with the greatest density of CB1 protein observed in the combined hippocampal subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3 hippocampal regions was significantly decreased in the dtg APP(swe)/PS1(ΔE9) mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APP(swe)/PS1(ΔE9) mice was associated with astroglial proliferation and elevated expression of the cytokines inducible nitric oxide synthase and tumor necrosis factor alpha. This finding suggests an anti-inflammatory effect of cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor expression may result in diminished anti-inflammatory processes, exacerbating the neuropathology associated with Alzheimer's disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Utilization of APPswe/PS1dE9 Transgenic Mice in Research of Alzheimer's Disease: Focus on Gene Therapy and Cell-Based Therapy Applications

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    Tarja Malm

    2011-01-01

    Full Text Available One of the most extensively used transgenic mouse model of Alzheimer’s disease (AD is APPswe/PS1dE9 mice, which over express the Swedish mutation of APP together with PS1 deleted in exon 9. These mice show increase in parenchymal Aβ load with Aβ plaques starting from the age of four months, glial activation, and deficits in cognitive functions at the age of 6 months demonstrated by radial arm water maze and 12-13 months seen with Morris Water Maze test. As gene transfer technology allows the delivery of DNA into target cells to achieve the expression of a protective or therapeutic protein, and stem cell transplantation may create an environment supporting neuronal functions and clearing Aβ plaques, these therapeutic approaches alone or in combination represent potential therapeutic strategies that need to be tested in relevant animal models before testing in clinics. Here we review the current utilization of APPswe/PS1dE9 mice in testing gene transfer and cell transplantation aimed at improving the protection of the neurons against Aβ toxicity and also reducing the brain levels of Aβ. Both gene therapy and cell based therapy may be feasible therapeutic approaches for human AD.

  5. Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Iván Carrera

    2013-01-01

    Full Text Available APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Our findings showed that administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before onset of Aβ deposition (7 weeks of age and/or at an older age (35 weeks of age is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

  6. Cinética de sinterização para sistemas à base de SnO2 por taxa de aquecimento constante Sintering kinetics for SnO2-based systems by constant heating rate

    Directory of Open Access Journals (Sweden)

    S. M. Tebcheran

    2003-04-01

    in small concentrations as densifying aids for this oxide. In the present study the sintering kinetics of tin oxide was studied considering the effect of sintering atmosphere and of the MnO2 concentration. SnO2-MnO2 systems were prepared from the polymeric precursors method and the obtained powders were characterized by surface area by the BET method. SnO2 powders with varied MnO2 concentrations were pressed in cylindrical shape, and sintered in a dilatometer furnace with constant heating rate and controlled atmospheres. Sintered samples were characterized by scanning electron microscopy. The influence of atmosphere (argon, air or CO2 as well as of the MnO2 concentrations on the sintering kinetics was determined. The kinetics data of linear shrinkage were analyzed in terms of kinetic models for the initial stage of sintering (Woolfrey and Bannister as well as for the global sintering (Su e Johnson allowing the determination of the apparent activation energy. Following the determination of the master sintering curve the apparent activation energy of all sintering process were determined as well as its dependence with the atmosphere and manganese concentrations. Based on these values and on the n exponent, determined by the classical grain growth equation, it was concluded that the most probable sintering mechanism is grain boundary diffusion with surface redistribution controlling the kinetics.

  7. Rate Constant and RRKM Product Study for the Reaction Between CH3 and C2H3 at T = 298K

    Science.gov (United States)

    Thorn, R. Peyton, Jr.; Payne, Walter A., Jr.; Chillier, Xavier D. F.; Stief, Louis J.; Nesbitt, Fred L.; Tardy, D. C.

    2000-01-01

    The total rate constant k1 has been determined at P = 1 Torr nominal pressure (He) and at T = 298 K for the vinyl-methyl cross-radical reaction CH3 + C2H3 yields products. The measurements were performed in a discharge flow system coupled with collision-free sampling to a mass spectrometer operated at low electron energies. Vinyl and methyl radicals were generated by the reactions of F with C2H4 and CH4, respectively. The kinetic studies were performed by monitoring the decay of C2H3 with methyl in excess, 6 rate coefficient was determined to be k1(298 K) = (1.02 +/- 0.53)x10(exp -10) cubic cm/molecule/s with the quoted uncertainty representing total errors. Numerical modeling was required to correct for secondary vinyl consumption by reactions such as C2H3 + H and C2H3 + C2H3. The present result for k1 at T = 298 K is compared to two previous studies at high pressure (100-300 Torr He) and to a very recent study at low pressure (0.9-3.7 Torr He). Comparison is also made with the rate constant for the similar reaction CH3 + C2H5 and with a value for k1 estimated by the geometric mean rule employing values for k(CH3 + CH3) and k(C2H3 + C2H3). Qualitative product studies at T = 298 K and 200 K indicated formation of C3H6, C2H2, and C2H5 as products of the combination-stabilization, disproportionation, and combination-decomposition channels, respectively, of the CH3 + C2H3 reaction. We also observed the secondary C4H8 product of the subsequent reaction of C3H5 with excess CH3; this observation provides convincing evidence for the combination-decomposition channel yielding C3H5 + H. RRKM calculations with helium as the deactivator support the present and very recent experimental observations that allylic C-H bond rupture is an important path in the combination reaction. The pressure and temperature dependencies of the branching fractions are also predicted.

  8. Time since death and decay rate constants of Norway spruce and European larch deadwood in subalpine forests determined using dendrochronology and radiocarbon dating

    Science.gov (United States)

    Petrillo, Marta; Cherubini, Paolo; Fravolini, Giulia; Marchetti, Marco; Ascher-Jenull, Judith; Schärer, Michael; Synal, Hans-Arno; Bertoldi, Daniela; Camin, Federica; Larcher, Roberto; Egli, Markus

    2016-03-01

    Due to the large size (e.g. sections of tree trunks) and highly heterogeneous spatial distribution of deadwood, the timescales involved in the coarse woody debris (CWD) decay of Picea abies (L.) Karst. and Larix decidua Mill. in Alpine forests are largely unknown. We investigated the CWD decay dynamics in an Alpine valley in Italy using the chronosequence approach and the five-decay class system that is based on a macromorphological assessment. For the decay classes 1-3, most of the dendrochronological samples were cross-dated to assess the time that had elapsed since tree death, but for decay classes 4 and 5 (poorly preserved tree rings) radiocarbon dating was used. In addition, density, cellulose, and lignin data were measured for the dated CWD. The decay rate constants for spruce and larch were estimated on the basis of the density loss using a single negative exponential model, a regression approach, and the stage-based matrix model. In the decay classes 1-3, the ages of the CWD were similar and varied between 1 and 54 years for spruce and 3 and 40 years for larch, with no significant differences between the classes; classes 1-3 are therefore not indicative of deadwood age. This seems to be due to a time lag between the death of a standing tree and its contact with the soil. We found distinct tree-species-specific differences in decay classes 4 and 5, with larch CWD reaching an average age of 210 years in class 5 and spruce only 77 years. The mean CWD rate constants were estimated to be in the range 0.018 to 0.022 y-1 for spruce and to about 0.012 y-1 for larch. Snapshot sampling (chronosequences) may overestimate the age and mean residence time of CWD. No sampling bias was, however, detectable using the stage-based matrix model. Cellulose and lignin time trends could be derived on the basis of the ages of the CWD. The half-lives for cellulose were 21 years for spruce and 50 years for larch. The half-life of lignin is considerably higher and may be more than

  9. Radical scavenging ability of gallic acid toward OH and OOH radicals. Reaction mechanism and rate constants from the density functional theory.

    Science.gov (United States)

    Marino, Tiziana; Galano, Annia; Russo, Nino

    2014-09-04

    Gallic acid is a ubiquitous compound, widely distributed in the vegetal kingdom and frequently found in the human diet. In the present work, its primary antioxidant activity has been investigated using the density functional theory (DFT), and the quantum mechanics-based test for overall free radical scavenging activity (QM-ORSA) protocol. It was found that gallic acid is a better antioxidant than the reference compound, Trolox, regardless of the polarity of the environment. In addition, gallic acid is predicted to be among the best peroxyl radical scavengers identified so far in nonpolar (lipid) media. This compound is capable of scavenging hydroxyl radicals at diffusion-limited rates, and hydroperoxyl radicals with rate constants in the order of 10(5) M(-1) s(-1). The deprotonation of gallic acid, in aqueous solution, is predicted to increase the protective action of this compound against oxidative stress. Gallic acid was also identified as a versatile scavenger, capable of rapidly deactivating a wide variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) via electron transfer at physiological pH.

  10. A comparison of methods to estimate anaerobic capacity: Accumulated oxygen deficit and W' during constant and all-out work-rate profiles.

    Science.gov (United States)

    Muniz-Pumares, Daniel; Pedlar, Charles; Godfrey, Richard; Glaister, Mark

    2017-12-01

    This study investigated (i) whether the accumulated oxygen deficit (AOD) and curvature constant of the power-duration relationship (W') are different during constant work-rate to exhaustion (CWR) and 3-min all-out (3MT) tests and (ii) the relationship between AOD and W' during CWR and 3MT. Twenty-one male cyclists (age: 40 ± 6 years; maximal oxygen uptake [V̇O2max]: 58 ± 7 ml · kg(-1) · min(-1)) completed preliminary tests to determine the V̇O2-power output relationship and V̇O2max. Subsequently, AOD and W' were determined as the difference between oxygen demand and oxygen uptake and work completed above critical power, respectively, in CWR and 3MT. There were no differences between tests for duration, work, or average power output (P ≥ 0.05). AOD was greater in the CWR test (4.18 ± 0.95 vs. 3.68 ± 0.98 L; P = 0.004), whereas W' was greater in 3MT (9.55 ± 4.00 vs. 11.37 ± 3.84 kJ; P = 0.010). AOD and W' were significantly correlated in both CWR (P W' in CWR and 3MT, between-test differences in the magnitude of AOD and W', suggest that both measures have different underpinning mechanisms.

  11. Rate and equilibrium constant of the reaction of 1-methylvinoxy radicals with O2: CH3COCH2 + O2 CH3COCH2O2.

    Science.gov (United States)

    Hassouna, Melynda; Delbos, Eric; Devolder, Pascal; Viskolcz, Bela; Fittschen, Christa

    2006-06-01

    The reaction of 1-methylvinoxy radicals, CH3COCH2, with molecular oxygen has been investigated by experimental and theoretical methods as a function of temperature (291-520 K) and pressure (0.042-10 bar He). Experiments have been performed by laser photolysis coupled to a detection of 1-methylvinoxy radicals by laser-induced fluorescence LIF. The potential energy surface calculations were performed using ab inito molecular orbital theory at the G3MP2B3 and CBSQB3 level of theory based on the density function theory optimized geometries. Derived molecular properties of the characteristic points of the potential energy surface were used to describe the mechanism and kinetics of the reaction under investigation. At 295 K, no pressure dependence of the rate constant for the association reaction has been observed: k(1,298K) = (1.18 +/- 0.04) x 10(-12) cm3 s(-1). Biexponential decays have been observed in the temperature range 459-520 K and have been interpreted as an equilibrium reaction. The temperature-dependent equilibrium constants have been extracted from these decays and a standard reaction enthalpy of deltaH(r,298K) = -105.0 +/- 2.0 kJ mol(-1) and entropy of deltaS(r,298K) = -143.0 +/- 4.0 J mol(-1) K(-1) were derived, in excellent agreement with the theoretical results. Consistent heats of formation for the vinoxy and the 1-methylvinoxy radical as well as their O2 adducts are recommended based on our complementary experimental and theoretical study deltaH(f,298K) = 13.0 +/- 2.0, -32. 9+/- 2.0, -85.9 +/- 4.0, and -142.1 +/- 4.0 kJ mol(-1) for CH2CHO, CH3COCH2 radicals, and their adducts, respectively.

  12. Modeling the pH and temperature dependence of aqueousphase hydroxyl radical reaction rate constants of organic micropollutants using QSPR approach.

    Science.gov (United States)

    Gupta, Shikha; Basant, Nikita

    2017-11-01

    Designing of advanced oxidation process (AOP) requires knowledge of the aqueous phase hydroxyl radical ( ● OH) reactions rate constants (k OH ), which are strictly dependent upon the pH and temperature of the medium. In this study, pH- and temperature-dependent quantitative structure-property relationship (QSPR) models based on the decision tree boost (DTB) approach were developed for the prediction of k OH of diverse organic contaminants following the OECD guidelines. Experimental datasets (n = 958) pertaining to the k OH values of aqueous phase reactions at different pH (n = 470; 1.4 × 10 6 to 3.8 × 10 10  M -1  s -1 ) and temperature (n = 171; 1.0 × 10 7 to 2.6 × 10 10  M -1  s -1 ) were considered and molecular descriptors of the compounds were derived. The Sanderson scale electronegativity, topological polar surface area, number of double bonds, and halogen atoms in the molecule, in addition to the pH and temperature, were found to be the relevant predictors. The models were validated and their external predictivity was evaluated in terms of most stringent criteria parameters derived on the test data. High values of the coefficient of determination (R 2 ) and small root mean squared error (RMSE) in respective training (> 0.972, ≤ 0.12) and test (≥ 0.936, ≤ 0.16) sets indicated high generalization and predictivity of the developed QSPR model. Other statistical parameters derived from the training and test data also supported the robustness of the models and their suitability for screening new chemicals within the defined chemical space. The developed QSPR models provide a valuable tool for predicting the ● OH reaction rate constants of emerging new water contaminants for their susceptibility to AOPs.

  13. Calculations with spectroscopic accuracy for energies, transition rates, hyperfine interaction constants, and Landé gJ-factors in nitrogen-like Kr XXX

    Science.gov (United States)

    Wang, K.; Li, S.; Jönsson, P.; Fu, N.; Dang, W.; Guo, X. L.; Chen, C. Y.; Yan, J.; Chen, Z. B.; Si, R.

    2017-01-01

    Extensive self-consistent multi-configuration Dirac-Fock (MCDF) calculations and second-order many-body perturbation theory (MBPT) calculations are performed for the lowest 272 states belonging to the 2s22p3, 2s2p4, 2p5, 2s22p23l, and 2s2p33l (l=s, p, d) configurations of N-like Kr XXX. Complete and consistent data sets of level energies, wavelengths, line strengths, oscillator strengths, lifetimes, AJ, BJ hyperfine interaction constants, Landé gJ-factors, and electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), magnetic quadrupole (M2) transition rates among all these levels are given. The present MCDF and MBPT results are compared with each other and with other available experimental and theoretical results. The mean relative difference between our two sets of level energies is only about 0.003% for these 272 levels. The accuracy of the present calculations are high enough to facilitate identification of many observed spectral lines. These accurate data can be served as benchmark for other calculations and can be useful for fusion plasma research and astrophysical applications.

  14. Accurate quantum mechanical calculations of differential and integral cross sections and rate constant for the O+OH reaction using an ab initio potential energy surface.

    Science.gov (United States)

    Lin, Shi Ying; Guo, Hua; Honvault, Pascal; Xu, Chuanxiu; Xie, Daiqian

    2008-01-07

    The authors report accurate quantum mechanical studies of the O+OH reaction on the improved Xu-Xie-Zhang-Lin-Guo potential energy surface. The differential cross section was obtained at several energies near the reaction threshold using a time-independent method. The dominant forward and backward peaks in the angular distribution are consistent with a complex-forming mechanism, which is also confirmed by the extensive rotational excitation in the O2 product. However, the asymmetry of these peaks suggests a significant nonstatistical component. The initial state (upsilon i=0, j i=0) specified integral cross section, which was calculated up to 1.15 eV of collision energy using the Chebyshev wave packet method, shows no energy threshold and decreases with the increasing collision energy, consistent with the barrierless nature of the reaction. The resulting rate constant exhibits a negative temperature dependence for T>100 K and decays as the temperature is lowered, in qualitative agreement with available experimental data.

  15. Toward the Development of a Fundamentally Based Chemical Model for Cyclopentanone: High-Pressure-Limit Rate Constants for H Atom Abstraction and Fuel Radical Decomposition.

    Science.gov (United States)

    Zhou, Chong-Wen; Simmie, John M; Pitz, William J; Curran, Henry J

    2016-09-15

    Theoretical aspects of the development of a chemical kinetic model for the pyrolysis and combustion of a cyclic ketone, cyclopentanone, are considered. Calculated thermodynamic and kinetic data are presented for the first time for the principal species including 2- and 3-oxo-cyclopentyl radicals, which are in reasonable agreement with the literature. These radicals can be formed via H atom abstraction reactions by Ḣ and Ö atoms and ȮH, HȮ2, and ĊH3 radicals, the rate constants of which have been calculated. Abstraction from the β-hydrogen atom is the dominant process when ȮH is involved, but the reverse holds true for HȮ2 radicals. The subsequent β-scission of the radicals formed is also determined, and it is shown that recent tunable VUV photoionization mass spectrometry experiments can be interpreted in this light. The bulk of the calculations used the composite model chemistry G4, which was benchmarked in the simplest case with a coupled cluster treatment, CCSD(T), in the complete basis set limit.

  16. Behavioral and neurobiological effects of prenatal stress exposure in male and female APPswe/PS1dE9 mice.

    Science.gov (United States)

    Sierksma, Annerieke S R; Prickaerts, Jos; Chouliaras, Leonidas; Rostamian, Somayeh; Delbroek, Lore; Rutten, Bart P F; Steinbusch, Harry W M; van den Hove, Daniel L A

    2013-01-01

    Epidemiological evidence implies a role for chronic stress and stress-related disorders in the etiopathogenesis of sporadic Alzheimer's disease (AD). Although chronic stress exposure during various stages of life has been shown to exacerbate AD-related cognitive deficits and neuropathology in AD mouse models, the role of stress exposure during the prenatal period on AD development and progression remained to be investigated. The present study therefore explored the effects of prenatal maternal stress (PMS) in both male and female APPswe/PS1dE9 mouse offspring in terms of cognition, affect, and AD-related neuropathology. As prenatal perturbations are likely to mediate their effects via alterations in epigenetic regulation, changes in hippocampal DNA methyltransferase 3a, 5-methylcytosine and 5-hydroxymethylcytosine levels were assessed as underlying mechanisms. Repetitive restraint stress during the first week of gestation exerted a sex-dependent effect, with male PMS mice showing spatial memory deficits and a blunted hypothalamus-pituitary-adrenal axis response, while female PMS mice showed improved spatial memory performance, increased depressive-like behavior, as well as a decrease in hippocampal plaque load. In addition, sex differences were observed among APPswe/PS1dE9 mice, independent of PMS (i.e., female mice showed impaired spatial memory performance, higher hippocampal plaque load, altered amyloid precursor protein processing in the CA3 and lower DNA methyltransferase 3a immunoreactivity in the dentate gyrus when compared with male mice of the same age). In conclusion, PMS exposure impacts on the behavioral phenotype and neuropathology of APPswe/PS1dE9 mice. Moreover, given the remarkable sex differences observed, one should not overlook the impact of sex-specific responses to environmental exposures when investigating gene-environment interactions in AD. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer's disease-related pathologies in APPswe/PS1dE9 transgenic mice.

    Science.gov (United States)

    Tsai-Teng, Tzeng; Chin-Chu, Chen; Li-Ya, Lee; Wan-Ping, Chen; Chung-Kuang, Lu; Chien-Chang, Shen; Chi-Ying, Huang F; Chien-Chih, Chen; Shiao, Young-Ji

    2016-06-27

    The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer's disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer's disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease are studied. After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aβ plaque burden. It's worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice. These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer's disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer's disease.

  18. Hippocampal Lipid Homeostasis in APP/PS1 Mice is Modulated by a Complex Interplay Between Dietary DHA and Estrogens: Relevance for Alzheimer's Disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Casañas-Sánchez, Verónica; Marin, Raquel; Gómez, Tomás; Quinto-Alemany, David; Pérez, José A

    2016-01-01

    Current evidence suggests that lipid homeostasis in the hippocampus is affected by different genetic, dietary, and hormonal factors, and that its deregulation may be associated with the onset and progression of Alzheimer's disease (AD). However, the precise levels of influence of each of these factors and their potential interactions remain largely unknown, particularly during neurodegenerative processes. In the present study, we have performed multifactorial analyses of the combined effects of diets containing different doses of docosahexaenoic acid (DHA), estrogen status (ovariectomized animals receiving vehicle or 17β-estradiol), and genotype (wild-type or transgenic APP/PS1 mice) in hippocampal lipid profiles. We have observed that the three factors affect lipid classes and fatty acid composition to different extents, and that strong interactions between these factors exist. The most aberrant lipid profiles were observed in APP/PS1 animals receiving DHA-poor diets and deprived of estrogens. Conversely, wild-type animals under a high-DHA diet and receiving estradiol exhibited a lipid profile that closely resembled that of the hippocampus of control animals. Interestingly, though the lipid signatures of APP/PS1 hippocampi markedly differed from wild-type, administration of a high-DHA diet in the presence of estrogens gave rise to a lipid profile that approached that of control animals. Paralleling changes in lipid composition, patterns of gene expression of enzymes involved in lipid biosynthesis were also altered and affected by combination of experimental factors. Overall, these results indicate that hippocampal lipid homeostasis is strongly affected by hormonal and dietary conditions, and that manipulation of these factors might be incorporated in AD therapeutics.

  19. Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in APP/PS1 mice used as a model of familial Alzheimer's disease.

    Science.gov (United States)

    Aso, Ester; Semakova, Jana; Joda, Laura; Semak, Vladislav; Halbaut, Lyda; Calpena, Ana; Escolano, Carmen; Perales, Jose C; Ferrer, Isidro

    2013-03-01

    Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer's disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer's disease.

  20. Immunocytochemical Characterization of Alzheimer’s Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Ivan Carrera

    2014-03-01

    Full Text Available Introduction: APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for the human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD. Material and methods: In this novel vaccine, a new approach has been taken to circumvent past failures with Aβ vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Results: Our findings showed that the administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before the onset of Aβ brain deposition (at 7 weeks of age and/or at an older age (35 weeks of age can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. Conclusion: These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

  1. In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Yuan-Yuan [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Li, Mu-Wei; Oishi, Kenichi [The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Zhang, Shun; Zhang, Yan; Zhao, Ling-Yun; Zhu, Wen-Zhen [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); Lei, Hao [Chinese Academy of Sciences, Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Wuhan (China)

    2013-08-15

    Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the

  2. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1 Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Henrik H Hansen

    Full Text Available One of the major histopathological hallmarks of Alzheimer's disease (AD is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1 receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP and presenilin-1 (PS1 are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9 of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c., or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.. In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  3. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer’s Disease

    Science.gov (United States)

    Barkholt, Pernille; Kongsbak-Wismann, Pernille; Schlumberger, Chantal; Jelsing, Jacob; Terwel, Dick; Termont, Annelies; Pyke, Charles; Knudsen, Lotte Bjerre; Vrang, Niels

    2016-01-01

    One of the major histopathological hallmarks of Alzheimer’s disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer’s disease carrying different clinical APP/PS1 mutations, i.e. the ‘London’ (hAPPLon/PS1A246E) and ‘Swedish’ mutation variant (hAPPSwe/PS1ΔE9) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD. PMID:27421117

  4. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Science.gov (United States)

    Hansen, Henrik H; Fabricius, Katrine; Barkholt, Pernille; Kongsbak-Wismann, Pernille; Schlumberger, Chantal; Jelsing, Jacob; Terwel, Dick; Termont, Annelies; Pyke, Charles; Knudsen, Lotte Bjerre; Vrang, Niels

    2016-01-01

    One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E) and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  5. Evaluation of gastric emptying time, gastrointestinal transit time, sedation score, and nausea score associated with intravenous constant rate infusion of lidocaine hydrochloride in clinically normal dogs.

    Science.gov (United States)

    Johnson, Rebecca A; Kierski, Katharine R; Jones, Brian G

    2017-05-01

    OBJECTIVE To quantify nausea and sedation scores, gastric emptying time, and gastrointestinal transit time after IV administration of a lidocaine hydrochloride bolus followed by a constant rate infusion (CRI) in clinically normal dogs. ANIMALS 6 Beagles. PROCEDURES In a crossover study, dogs were fed thirty 1.5-mm barium-impregnated spheres (BIPS) and received a saline (0.9% NaCl) solution bolus (0.05 mL/kg) IV (time 0) followed by a CRI at 10 mL/h, a lidocaine bolus (1 mg/kg) IV followed by a CRI at 25 μg/kg/min, or a lidocaine bolus (1 mg/kg) IV followed by a CRI at 50 μg/kg/min; CRIs were for 12 hours. Nausea and sedation scores were assessed and abdominal radiographs obtained immediately after feeding of BIPS and every hour for 12 hours and again 16 hours after CRI start. Percentage of BIPSs in the small and large intestines, gastric emptying time, and gastrointestinal transit time were assessed. RESULTS Gastric emptying time did not differ significantly among treatments. Significantly more BIPS were in the large intestine 4 to 7 hours after treatment start for the 50-μg/kg/min treatment than for the other 2 treatments. Six hours after treatment start, significantly more BIPS were in the large intestine for the 25-μg/kg/min treatment than for the saline solution treatment. Higher sedation and nausea scores were associated with the 50-μg/kg/min CRI. CONCLUSIONS AND CLINICAL RELEVANCE In clinically normal dogs, lidocaine CRI did not significantly affect gastric emptying. However, gastrointestinal transit time was mildly decreased and sedation and nausea scores increased in dogs administered a lidocaine CRI at clinically used doses.

  6. Estimating the plasma effect-site equilibrium rate constant (Ke₀) of propofol by fitting time of loss and recovery of consciousness.

    Science.gov (United States)

    Wu, Qi; Sun, Baozhu; Wang, Shuqin; Zhao, Lianying; Qi, Feng

    2013-01-01

    The present paper proposes a new approach for fitting the plasma effect-site equilibrium rate constant (Ke0) of propofol to satisfy the condition that the effect-site concentration (Ce) is equal at the time of loss of consciousness (LOC) and recovery of consciousness (ROC). Forty patients receiving intravenous anesthesia were divided into 4 groups and injected propofol 1.4, 1.6, 1.8, or 2 mg/kg at 1,200 mL/h. Durations from the start of injection to LOC and to ROC were recorded. LOC and ROC were defined as an observer's assessment of alertness and sedation scale change from 3 to 2 and from 2 to 3, respectively. Software utilizing bisection method iteration algorithms was built. Then, Ke0 satisfying the CeLOC=CeROC condition was estimated. The accuracy of the Ke0 estimated by our method was compared with the Diprifusor TCI Pump built-in Ke0 (0.26 min(-1)), and the Orchestra Workstation built-in Ke0 (1.21 min(-1)) in another group of 21 patients who were injected propofol 1.4 to 2 mg/kg. Our results show that the population Ke0 of propofol was 0.53 ± 0.18 min(-1). The regression equation for adjustment by dose (mg/kg) and age was Ke0=1.42-0.30 × dose-0.0074 × age. Only Ke0 adjusted by dose and age achieved the level of accuracy required for clinical applications. We conclude that the Ke0 estimated based on clinical signs and the two-point fitting method significantly improved the ability of CeLOC to predict CeROC. However, only the Ke0 adjusted by dose and age and not a fixed Ke0 value can meet clinical requirements of accuracy.

  7. Effects of maintenance of propofol-ketamine anesthesia with repeat bolus and constant rate infusion of propofol on physiological, biochemical, anesthetic and analgesic indices in dogs

    National Research Council Canada - National Science Library

    Njoku, Njoku

    2015-01-01

    The research work was aimed at investigating physiological, biochemical, analgesic and anesthetic indices of dogs anesthetized with propofol-ketamine and maintained with repeat bolus and constant infusions of propofol...

  8. Hypochlorous acid-mediated oxidation of lipid components and antioxidants present in low-density lipoproteins: absolute rate constants, product analysis, and computational modeling.

    Science.gov (United States)

    Pattison, David I; Hawkins, Clare L; Davies, Michael J

    2003-04-01

    Oxidation of low-density lipoproteins (LDL) is believed to contribute to the increased uptake of LDL by macrophages, which is an early event in atherosclerosis. Hypochlorous acid (HOCl) has been implicated as one of the major oxidants involved in these processes. In a previous study, the rates of reaction of HOCl with the reactive sites in proteins were investigated (Pattison, D. I., and Davies, M. J. (2001) Chem. Res. Toxicol. 14, 1453-1464). The work presented here expands on those studies to determine absolute second-order rate constants for the reactions of HOCl with various lipid components and antioxidants in aqueous solution (pH 7.4). The reactions of HOCl with phosphoryl-serine and phosphoryl-ethanolamine are rapid (k approximately 10(5) M(-)(1) s(-)(1)) and of comparable reactivity to many of the protein sites. The major products formed in these reactions are chloramines, which decay to give both nitrogen- and carbon-centered radicals. Subsequent reactions of these species may induce oxidation of the LDL lipid component. In contrast, phosphoryl-choline reacted much more slowly (k < 10(-)(2) M(-)(1) s(-)(1)). Reaction of HOCl with 3-pentenoic acid was used as a model of lipid double bonds and yielded k = 9 M(-)(1) s(-)(1). The reactions of the lipid-soluble antioxidants, alpha-tocopherol and ubiquinol-10, with HOCl were investigated with model compounds. For the reactions of HOCl with both Trolox and ubiquinol-0, k = 1.3 x 10(3) M(-)(1) s(-)(1); thus, these lipid soluble antioxidants are relatively ineffective as direct scavengers for HOCl as compared to water soluble antioxidants (e.g., ascorbate, k ca. 10(6) M(-)(1) s(-)(1)). The reaction of HOCl with hydroquinone (a simple model for ubiquinol-10) was also investigated both in aqueous solution (k = 45 M(-)(1) s(-)(1)) and in a less polar environment (k approximately 0.5 M(-)(1) s(-)(1) in THF). A computational model was developed using these kinetic parameters to predict which LDL targets are oxidized

  9. Valproic acid ameliorates olfactory dysfunction in APP/PS1 transgenic mice of Alzheimer's disease: Ameliorations from the olfactory epithelium to the olfactory bulb.

    Science.gov (United States)

    Yao, Zhi-Gang; Jing, Hai-Yan; Wang, Dong-Mei; Lv, Bei-Bei; Li, Jia-Mei; Liu, Feng-Feng; Fan, Hui; Sun, Xi-Chao; Qin, Ye-Jun; Zhao, Miao-Qing

    2016-05-01

    Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Alzheimer's disease (AD) and mild cognitive impairment, pointing to the progression to dementia. Recent studies have revealed that valproic acid (VPA) has neuroprotective effects in rodent models of AD. In this study, we investigated the effects of VPA on olfactory dysfunction of APP/PS1 double transgenic mouse models of AD. After continuous treatment with a 100mg/kg daily dose of VPA for 3 months, APP/PS1 mice showed improved olfactory performances. In agreement with the behavioral findings, VPA treatment reduced amyloid β (Aβ) burden in the olfactory epithelium (OE) of transgenic mice. And, VPA increased epithelial thickness of the olfactory mucosa through decreased cell apoptosis and increased cell proliferation. In the olfactory bulb (OB), VPA administration also reduced senile plaques and levels of soluble and insoluble Aβ42 peptides. Besides, VPA promoted the increase of mitral cells and decrease of neurofilament immunostaining. In hence, VPA treatment completely improved the olfactory performances and prevented degenerative changes of the OE and OB. Our study raises the possibility of AD diagnosis by OE biopsy. Moreover, VPA may provide a novel therapeutic strategy for the treatment of olfactory dysfunction in AD patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Exercise-Induced Neuroprotection of Hippocampus in APP/PS1 Transgenic Mice via Upregulation of Mitochondrial 8-Oxoguanine DNA Glycosylase

    Directory of Open Access Journals (Sweden)

    Hai Bo

    2014-01-01

    Full Text Available Improving mitochondrial function has been proposed as a reasonable therapeutic strategy to reduce amyloid-β (Aβ load and to modify the progression of Alzheimer’s disease (AD. However, the relationship between mitochondrial adaptation and brain neuroprotection caused by physical exercise in AD is poorly understood. This study was undertaken to investigate the effects of long-term treadmill exercise on mitochondrial 8-oxoguanine DNA glycosylase-1 (OGG1 level, mtDNA oxidative damage, and mitochondrial function in the hippocampus of APP/PS1 transgenic mouse model of AD. In the present study, twenty weeks of treadmill training significantly improved the cognitive function and reduced the expression of Aβ-42 in APP/PS1 transgenic (Tg mice. Training also ameliorated mitochondrial respiratory function by increasing the complexes I, and IV and ATP synthase activities, whereas it attenuated ROS generation and mtDNA oxidative damage in Tg mice. Furthermore, the impaired mitochondrial antioxidant enzymes and mitochondrial OGG1 activities seen in Tg mice were restored with training. Acetylation level of mitochondrial OGG1 and MnSOD was markedly suppressed in Tg mice after exercise training, in parallel with increased level of SIRT3. These findings suggest that exercise training could increase mtDNA repair capacity in the mouse hippocampus, which in turn would result in protection against AD-related mitochondrial dysfunction and phenotypic deterioration.

  11. Long-term treadmill exercise improves spatial memory of male appswe/ps1de9 mice by regulation of BDNF expression and microglia activation

    Directory of Open Access Journals (Sweden)

    JY Xiong

    2015-11-01

    Full Text Available Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer’s disease (AD. But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P 0.05. The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.

  12. Antagonist of peroxisome proliferator-activated receptor {gamma} induces cerebellar amyloid-{beta} levels and motor dysfunction in APP/PS1 transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Du, Jing; Sun, Bing [Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084 (China); Chen, Kui [Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032 (China); Fan, Li [Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032 (China); Cardiovascular Research, Starr Academic Center, Providence Heart and Vascular Institute, Portland, OR 97225 (United States); Wang, Zhao, E-mail: zwang@tsinghua.edu.cn [Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084 (China)

    2009-07-03

    Recent evidences show that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is involved in the modulation of the amyloid-{beta} (A{beta}) cascade causing Alzheimer's disease (AD) and treatment with PPAR{gamma} agonists protects against AD pathology. However, the function of PPAR{gamma} steady-state activity in A{beta} cascade and AD pathology remains unclear. In this study, an antagonist of PPAR{gamma}, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPAR{gamma} activity in cerebellum. The results show that inhibition of PPAR{gamma} significantly induced A{beta} levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of A{beta}. Since cerebellum is spared from significant A{beta} accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPAR{gamma} steady-state activity in protection of cerebellum against AD pathology.

  13. Age-related changes in visual acuity, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Stover, Kurt R; Brown, Richard E

    2012-05-16

    Mouse models of Alzheimer's disease (AD) are often tested for learning and memory deficits using visuo-spatial tasks such as the Morris water maze. Performance on these tasks is dependent on vision and the APPswe/PS1dE9 mouse model has amyloid beta plaques in their retinas which might influence their performance in these tasks. In a visual learning task, old (20-26 months) transgenic mice and their wildtype littermates of both sexes had poorer visual ability than young (5-8 months) mice and old transgenic mice had poorer visual acuity than old wildtype mice. Old transgenic mice also had deficits in visuo-spatial learning and memory on the Morris water maze. The transgenic mice had no deficits in the conditioned odour preference or conditioned taste aversion memory tests at any age. These results indicate that the old APPswe/PS1dE9 mice and their wildtype littermates both have a deficit in their visual ability and that visually dependent measures alone should not be used to assess learning and memory in this strain. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.

    Science.gov (United States)

    Zhu, Lei; Yang, Jing-yu; Xue, Xue; Dong, Ying-xu; Liu, Yang; Miao, Feng-rong; Wang, Yong-feng; Xue, Hong; Wu, Chun-fu

    2015-09-01

    In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6 mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of Aβ plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+) cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  16. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  17. Comparison of the rate constants for energy transfer in the light-harvesting protein, C-phycocyanin, calculated from Foerster`s theory and experimentally measured by time-resolved fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Debreczeny, Martin Paul [Univ. of California, Berkeley, CA (United States)

    1994-05-01

    We have measured and assigned rate constants for energy transfer between chromophores in the light-harvesting protein C-phycocyanin (PC), in the monomeric and trimeric aggregation states, isolated from Synechococcus sp. PCC 7002. In order to compare the measured rate constants with those predicted by Fdrster`s theory of inductive resonance in the weak coupling limit, we have experimentally resolved several properties of the three chromophore types ({beta}{sub 155} {alpha}{sub 84}, {beta}{sub 84}) found in PC monomers, including absorption and fluorescence spectra, extinction coefficients, fluorescence quantum yields, and fluorescence lifetimes. The cpcB/C155S mutant, whose PC is missing the {beta}{sub 155} chromophore, was, useful in effecting the resolution of the chromophore properties and in assigning the experimentally observed rate constants for energy transfer to specific pathways.

  18. Rate constants for the gas-phase reactions of OH radicals with CH3CHF2 and CHCl2CF3 over the temperature range 295-388 K

    DEFF Research Database (Denmark)

    Nielsen, O.J.

    1991-01-01

    Rate constants for the reactions of OH radicals with CH3CHF2 and CHCl2CF3 have been determined over the temperature range 295-388 K and a total pressure of 1 atm. The OH rate data were obtained using the absolute rate technique of pulse radiolysis combined with kinetic spectroscopy. The data can...... and in the light of the important role CH3CHF2 and CHCl2CF3 play as alternatives to the fully halogenated chlorofluorocarbons....

  19. Full-dimensional analytical potential energy surface describing the gas-phase Cl + C2H6reaction and kinetics study of rate constants and kinetic isotope effects.

    Science.gov (United States)

    Rangel, Cipriano; Espinosa-Garcia, Joaquin

    2018-02-07

    Within the Born-Oppenheimer approximation a full-dimensional analytical potential energy surface, PES-2017, was developed for the gas-phase hydrogen abstraction reaction between the chlorine atom and ethane, which is a nine body system. This surface presents a valence-bond/molecular mechanics functional form dependent on 60 parameters and is fitted to high-level ab initio calculations. This reaction presents little exothermicity, -2.30 kcal mol -1 , with a low height barrier, 2.44 kcal mol -1 , and intermediate complexes in the entrance and exit channels. We found that the energetic description was strongly dependent on the ab initio level used and it presented a very flat topology in the entrance channel, which represents a theoretical challenge in the fitting process. In general, PES-2017 reproduces the ab initio information used as input, which is merely a test of self-consistency. As a first test of the quality of the PES-2017, a theoretical kinetics study was performed in the temperature range 200-1400 K using two approaches, i.e. the variational transition-state theory and quasi-classical trajectory calculations, with spin-orbit effects. The rate constants show reasonable agreement with experiments in the whole temperature range, with the largest differences at the lowest temperatures, and this behaviour agrees with previous theoretical studies, thus indicating the inherent difficulties in the theoretical simulation of the kinetics of the title reaction. Different sources of error were analysed, such as the limitations of the PES and theoretical methods, recrossing effects, and the tunnelling effect, which is negligible in this reaction, and the manner in which the spin-orbit effects were included in this non-relativistic study. We found that the variation of spin-orbit coupling along the reaction path, and the influence of the reactivity of the excited Cl( 2 P 1/2 ) state, have relative importance, but do not explain the whole discrepancy. Finally, the

  20. SU-E-P-55: The Reaserch of Cervical Cancer Delivered with Constant Dose Rate and Gantry Speed Arc Therapy(CDR-CAS-IMAT) On Conventional Linac

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R; Bai, W; Chi, Z; Gao, C; Xiaomei, F [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China); Gao, Y [Hebei General Hospital, Shijiazhuang, Hebei (China)

    2015-06-15

    Purpose: Postoperative cervical cancer patients with large target volume and the target shape is concave, treatmented with static intensity-modulated radiotherapy (IMRT) is time consuming. The purpose of this study is to investigate using constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) on conventional linear accelrator, by comparing with the IMRT technology to evaluate the performance of CDR-CAS-IMAT on postoperative cervical cancer patients. Methods: 18 cervical cancer patients treated with IMRT on Varian 23IX were replanted using CDR-CAS-IMAT. The plans were generated on Oncentra v4.1 planning system, PTV was prescribed to 50.4 Gy in 28 fractions. Plans were evaluated based on the ability to meet the dose volume histogram. The homogeneity index (HI), conformity index (CI) of target volume, the dose of organs at risk, radiation delivery time and monitor units were also compared. SPSS 19.0 software paired T-test analysis was carried out on the two sets of data. Results: Compared with the IMRT plans PTV’s CI (t= 3.85, P =0.001), CTV’s CI, HI, D90, D95, D98, V95, V98, V100 (t=4.21, −3.18, 2.13, 4.65, 7.79, 2.29, 6.00, 2.13, p=0.001, 0.005, 0.049, 0.000, 0.000, 0.035, 0.000, 0.049), and cord D2 and rectum V40 (t=−2.65, −2.47, p= P =0.017, 0.025), and treatment time and MU (t=−36.0, −6.26, P =0.000, 0.000) were better than that of IMRT group. But the IMRT plans in terms of decreasing bladder V50, bowel V30 (t=2.14, 3.00, P =0.048, 0.008) and low dose irradiation volume were superior to that of CDR-CAS-IMAT plans. There were no significant differences in other statistical index. Conclusion: Cervical cancer patients with CDR-CAS-IMAT on Varian Clinical 23IX can get equivalent or superior dose distribution compared with the IMRT technology. IMAT have much less treatment time and MU can reduce the uncertainty factor and patient discomfort in treatment. This work was supported by the Medical Science Foundation of the health department of Hebei

  1. Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2013-01-01

    in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels...

  2. Quasiclassical Trajectory Calculations of the Rate Constant of the OH + HBr → Br + H2O Reaction Using a Full-Dimensional Ab Initio Potential Energy Surface Over the Temperature Range 5 to 500 K.

    Science.gov (United States)

    de Oliveira-Filho, Antonio G S; Ornellas, Fernando R; Bowman, Joel M

    2014-02-20

    We report a permutationally invariant, ab initio potential energy surface (PES) for the OH + HBr → Br + H2O reaction. The PES is a fit to roughly 26 000 spin-free UCCSD(T)/cc-pVDZ-F12a energies and has no classical barrier to reaction. It is used in quasiclassical trajectory calculations with a focus on the thermal rate constant, k(T), over the temperature range 5 to 500 K. Comparisons with available experimental data over the temperature range 23 to 416 K are made using three approaches to treat the OH rotational and associated electronic partition function. All display an inverse temperature dependence of k(T) below roughly 160 K and a nearly constant temperature dependence above 160 K, in agreement with experiment. The calculated rate constant with no treatment of spin-orbit coupling is overall in the best agreement with experiment, being (probably fortuitously) within 20% of it.

  3. Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice

    DEFF Research Database (Denmark)

    Olesen, Louise Orum; Sivasaravanaparan, Mithula; Severino, Maurizio

    2017-01-01

    the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APPswe/PS1dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis......, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance...... in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial...

  4. Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice

    DEFF Research Database (Denmark)

    Ordóñez-Gutiérrez, Lara; Re, Francesca; Bereczki, Erika

    2015-01-01

    UNLABELLED: The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus......, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid...... Aβ may be therapeutically relevant in AD. FROM THE CLINICAL EDITOR: Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected...

  5. The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice.

    Science.gov (United States)

    Tzeng, Tsai-Teng; Chen, Chien-Chih; Chen, Chin-Chu; Tsay, Huey-Jen; Lee, Li-Ya; Chen, Wan-Ping; Shen, Chien-Chang; Shiao, Young-Ji

    2018-02-17

    Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.

  6. Antisense directed against PS-1 gene decreases brain oxidative markers in aged senescence accelerated mice (SAMP8) and reverses learning and memory impairment: a proteomics study

    Science.gov (United States)

    Fiorini, Ada; Sultana, Rukhsana; Förster, Sarah; Perluigi, Marzia; Cenini, Giovanna; Cini, Chiara; Cai, Jian; Klein, Jon B.; Farr, Susan A.; Niehoff, Michael L.; Morley, John E.; Kumar, Vijaya B.; Butterfield, D. Allan

    2013-01-01

    Amyloid β-peptide (Aβ) plays a central role in pathophysiology of Alzheimer’s disease (AD) through the induction of oxidative stress. This peptide is produced by proteolytic cleavage of amyloid precursor protein (APP) by the action of β- and γ-secretases. Previous studies demonstrated that reduction of Aβ, using an antisense oligonucleotide (AO) directed against the Aβ region of APP, reduced oxidative stress-mediated damage and prevented or reverted cognitive deficits in senescence-accelerated prone mice (SAMP8), a useful animal model to investigate the events related to Aβ pathology and possibly to the early phase of AD. In the current study, aged SAMP8 were treated by AO directed against PS-1, a component of the γ-secretase complex, and tested for learning and memory in T-maze foot shock avoidance and novel object recognition. Brain tissue was collected to identify the decrease of oxidative stress and to evaluate the proteins that are differently expressed and oxidized after the reduction in free radical levels induced by Aβ. We used both expression proteomics and redox proteomics approaches. In brain of AO-treated mice a decrease of oxidative stress markers was found, and the proteins identified by proteomics as expressed differently or nitrated are involved in processes known to be impaired in AD. Our results suggest that the treatment with AO directed against PS-1 in old SAMP8 mice reverses learning and memory deficits and reduces Aβ-mediated oxidative stress with restoration to the normal condition and identifies possible pharmacological targets to combat this devastating dementing disease. PMID:23777706

  7. Interleukin-1β mediated amyloid plaque clearance is independent of CCR2 signaling in the APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Rivera-Escalera, Fátima; Matousek, Sarah B; Ghosh, Simantini; Olschowka, John A; O'Banion, M Kerry

    2014-09-01

    Neuroinflammation is a key component of Alzheimer's disease (AD) pathogenesis. Particularly, the proinflammatory cytokine interleukin-1 beta (IL-1β) is upregulated in human AD and believed to promote amyloid plaque deposition. However, studies from our laboratory have shown that chronic IL-1β overexpression in the APPswe/PSEN1dE9 (APP/PS1) mouse model of AD ameliorates amyloid pathology, increases plaque-associated microglia, and induces recruitment of peripheral immune cells to the brain parenchyma. To investigate the contribution of CCR2 signaling in IL-1β-mediated amyloid plaque clearance, seven month-old APP/PS1/CCR2(-/-) mice were intrahippocampally transduced with a recombinant adeno-associated virus serotype 2 containing the cleaved form of human IL-1β (rAAV2-IL-1β). Four weeks after rAAV2-IL-1β transduction, we found significant reductions in 6E10 and Congo red staining of amyloid plaques that was confirmed by decreased levels of insoluble Aβ1-42 and Aβ1-40 in the inflamed hippocampus. Bone marrow chimeric studies confirmed the presence of infiltrating immune cells following IL-1β overexpression and revealed that dramatic reduction of CCR2(+) peripheral mononuclear cell recruitment to the inflamed hippocampus did not prevent the ability of IL-1β to induce amyloid plaque clearance. These results suggest that infiltrating CCR2(+) monocytes do not contribute to IL-1β-mediated amyloid plaque clearance. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Detection by voxel-wise statistical analysis of significant changes in regional cerebral glucose uptake in an APP/PS1 transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Dubois, Albertine; Hérard, Anne-Sophie; Delatour, Benoît; Hantraye, Philippe; Bonvento, Gilles; Dhenain, Marc; Delzescaux, Thierry

    2010-06-01

    Biomarkers and technologies similar to those used in humans are essential for the follow-up of Alzheimer's disease (AD) animal models, particularly for the clarification of mechanisms and the screening and validation of new candidate treatments. In humans, changes in brain metabolism can be detected by 1-deoxy-2-[(18)F] fluoro-D-glucose PET (FDG-PET) and assessed in a user-independent manner with dedicated software, such as Statistical Parametric Mapping (SPM). FDG-PET can be carried out in small animals, but its resolution is low as compared to the size of rodent brain structures. In mouse models of AD, changes in cerebral glucose utilization are usually detected by [(14)C]-2-deoxyglucose (2DG) autoradiography, but this requires prior manual outlining of regions of interest (ROI) on selected sections. Here, we evaluate the feasibility of applying the SPM method to 3D autoradiographic data sets mapping brain metabolic activity in a transgenic mouse model of AD. We report the preliminary results obtained with 4 APP/PS1 (64+/-1 weeks) and 3 PS1 (65+/-2 weeks) mice. We also describe new procedures for the acquisition and use of "blockface" photographs and provide the first demonstration of their value for the 3D reconstruction and spatial normalization of post mortem mouse brain volumes. Despite this limited sample size, our results appear to be meaningful, consistent, and more comprehensive than findings from previously published studies based on conventional ROI-based methods. The establishment of statistical significance at the voxel level, rather than with a user-defined ROI, makes it possible to detect more reliably subtle differences in geometrically complex regions, such as the hippocampus. Our approach is generic and could be easily applied to other biomarkers and extended to other species and applications. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

    Science.gov (United States)

    Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  10. Determination of the rate constant for the OH(X2Π) + OH(X2Π) → H2O + O(3P) reaction over the temperature range 295 to 701 K.

    Science.gov (United States)

    Altinay, Gokhan; Macdonald, R Glen

    2014-01-09

    The rate constant for the radical-radical reaction OH(X(2)Π) + OH(X(2)Π) → H2O + O((3)P) has been measured over the temperature and pressure ranges 295-701 K and 2-12 Torr, respectively, in mixtures of CF4, N2O, and H2O. The OH radical was produced by the 193 nm laser photolysis of N2O. The resulting O((1)D) atoms reacted rapidly with H2O to produce the OH radical. The OH radical was detected by high-resolution time-resolved infrared absorption spectroscopy using a single Λ-doublet component of the OH(1,0) P1e/f(4.5) fundamental vibrational transition. A detailed kinetic model was used to determine the reaction rate constant as a function of temperature. These experiments were conducted in a new temperature controlled reaction chamber. The values of the measured rate constants are quite similar to the previous measurements from this laboratory of Bahng and Macdonald (J. Phys. Chem. A 2007 , 111 , 3850 - 3861); however, they cover a much larger temperature range. The results of the present work do not agree with recent measurements of Sangwan and Krasnoperov (J. Phys. Chem. A 2012 , 116 , 11817 - 11822). At 295 K the rate constant of the title reaction was found to be (2.52 ± 0.63) × 10(-12) cm(3) molecule(-1) s(-1), where the uncertainty includes both experimental scatter and an estimate of systematic errors at the 95% confidence limit. Over the temperature range of the experiments, the rate constant can be represented by k1a = 4.79 × 10(-18)T(1.79) exp(879.0/T) cm(3) molecule(-1) s(-1) with a uncertainty of ±24% at the 2σ level, including experimental scatter and systematic error.

  11. Photochemical properties of trans-1-chloro-3,3,3-trifluoropropene (trans-CHCl═CHCF3): OH reaction rate constant, UV and IR absorption spectra, global warming potential, and ozone depletion potential.

    Science.gov (United States)

    Orkin, Vladimir L; Martynova, Larissa E; Kurylo, Michael J

    2014-07-17

    Measurements of the rate constant for the gas-phase reactions of OH radicals with trans-1-chloro-3,3,3-trifluoropropene (trans-CHCl═CHCF3) were performed using a flash photolysis resonance-fluorescence technique over the temperature range 220-370 K. The reaction rate constant exhibits a noticeable curvature of the temperature dependence in the Arrhenius plot, which can be represented by the following expression: kt-CFP (220-370 K) = 1.025 × 10(-13) × (T/298)(2.29) exp(+384/T) cm(3 )molecule(-1) s(-1). The room-temperature rate constant was determined to be kt-CFP (298 K) = (3.29 ± 0.10) × 10(-13) cm(3) molecule(-1) s(-1), where the uncertainty includes both two standard errors (statistical) and the estimated systematic error. For atmospheric modeling purposes, the rate constant below room temperature can be represented by the following expression: kt-CFP (220-298 K) = (7.20 ± 0.46) × 10(-13) exp[-(237 ± 16)/T] cm(3) molecule(-1) s(-1). There was no difference observed between the rate constants determined at 4 kPa (30 Torr) and 40 kPa (300 Torr) at both 298 and 370 K. The UV and IR absorption cross sections of this compound were measured at room temperature. The atmospheric lifetime, global warming potential, and ozone depletion potential of trans-CHCl═CHCF3 were estimated.

  12. A direct comparison of U.S. Environmental Protection Agency's method 304B and batch tests for determining activated-sludge biodegradation rate constants for volatile organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Cano, M.L.; Wilcox, M.E.; Compernolle, R. van

    1999-12-01

    Biodegradation rate constants for volatile organic compounds (VOCs) in activated-sludge systems are needed to quantify emissions. One current US environmental Protection Agency method for determining a biodegradation rate constant is Method 304B. In this approach, a specific activated-sludge unit is simulated by a continuous biological treatment system with a sealed headspace. Batch experiments, however, can be alternatives to Method 304B. Two of these batch methods are the batch test that uses oxygen addition (BOX) and the serum bottle test (SBT). In this study, Method 304B was directly compared to BOX and SBT experiments. A pilot-scale laboratory reactor was constructed to serve as the Method 304B unit. Biomass from the unit was also used to conduct BOX and modified SBT experiments (modification involved use of a sealed draft-tube reactor with a headspace recirculation pump instead of a serum bottle) for 1,2-dichloroethane, diisopropyl ether, methyl tertiary butyl ether, and toluene. Three experimental runs--each consisting of one Method 304B experiment, one BOX experiment, and one modified SBT experiment--were completed. The BOX and SBT data for each run were analyzed using a Monod model, and best-fit biodegradation kinetic parameters were determined for each experiment, including a first-order biodegradation rate constant (K{sub 1}). Experimental results suggest that for readily biodegradable VOCs the two batch techniques can provide improved means of determining biodegradation rate constants compared with Method 304B. In particular, these batch techniques avoid the Method 304B problem associated with steady-state effluent concentrations below analytical detection limits. However, experimental results also suggest that the two batch techniques should not be used to determine biodegradation rate constants for slowly degraded VOCs (i.e., K{sub 1} {lt} 0.1 L/g VSS-h).

  13. How do Bacteria Adapt to the Red Sea? Cultivation and Genomic and Physiological Characterization of Oligotrophic Bacteria of the PS1, OM43, and SAR11 Clades

    KAUST Repository

    Jimenez Infante, Francy M.

    2015-05-01

    Given the high salinity, prevailing annual high temperatures, and ultra-oligotrophic conditions in the Red Sea isolation and characterization of important microbial groups thriving in this environment is important in understanding the ecological significance and metabolic capabilities of these communities. By using a high-­throughput cultivation technique in natural seawater amended with minute amounts of nutrients, members of the rare biosphere (PS1), methylotrophic Betaproteobacteria (OM43), and the ubiquitous and abundant SAR11 group (Pelagibacterales), were isolated in pure culture. Phylogenetic analyses of Red Sea isolates along with comparative genomics with close representatives from disparate provinces revealed ecotypes and genomic differentiation among the groups. Firstly, the PS1 alphaproteobacterial clade was found to be present in very low abundance in several metagenomic datasets form divergent environments. While strain RS24 (Red Sea) harbored genomic islands involved in polymer degradation, IMCC14465 (East (Japan) Sea) contained unique genes for degradation of aromatic compounds. Secondly, methylotrophic OM43 bacteria from the Red Sea (F5, G12 and H7) showed higher similarities with KB13 isolate from Hawaii, forming a ‘H-­RS’ (Hawaii-­Red Sea) cluster separate from HTCC2181 (Oregon isolate). HTCC2181 members were shown to prevail in cold, productive coastal environments and had an nqrA-­F system for energy generation by sodium motive force. On the contrary, H-­RS cluster members may be better adapted to warm and oligotrophic environments, and seem to generate energy by using a proton-­translocating NADH:Quinone oxidoreductase (complex I; nuoA-­N subunits). Moreover, F5, G12, and H7 had unique proteins related to resistance to UV, temperature and salinity, in addition to a heavy metal ‘resistance island’ as adaptive traits to cope with the environmental conditions in the Red Sea. Finally, description of the Red Sea Pelagibacterales

  14. Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene.

    Science.gov (United States)

    Zimmermann, Tomáš; Vaníček, Jiří

    2010-11-01

    Recent experiments have confirmed the importance of nuclear quantum effects even in large biomolecules at physiological temperature. Here we describe how the path integral formalism can be used to describe rigorously the nuclear quantum effects on equilibrium and kinetic properties of molecules. Specifically, we explain how path integrals can be employed to evaluate the equilibrium (EIE) and kinetic (KIE) isotope effects, and the temperature dependence of the rate constant. The methodology is applied to the [1,5] sigmatropic hydrogen shift in pentadiene. Both the KIE and the temperature dependence of the rate constant confirm the importance of tunneling and other nuclear quantum effects as well as of the anharmonicity of the potential energy surface. Moreover, previous results on the KIE were improved by using a combination of a high level electronic structure calculation within the harmonic approximation with a path integral anharmonicity correction using a lower level method.

  15. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease.

    Science.gov (United States)

    Saiz-Sanchez, Daniel; De La Rosa-Prieto, Carlos; Ubeda-Bañon, Isabel; Martinez-Marcos, Alino

    2013-09-01

    Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta-amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder. Copyright © 2013 Wiley Periodicals, Inc.

  16. Iron, Copper, and Zinc Concentration in Aβ Plaques in the APP/PS1 Mouse Model of Alzheimer's Disease Correlates with Metal Levels in the Surrounding Neuropil.

    Science.gov (United States)

    James, Simon A; Churches, Quentin I; de Jonge, Martin D; Birchall, Ian E; Streltsov, Victor; McColl, Gawain; Adlard, Paul A; Hare, Dominic J

    2017-03-15

    The metal ions of iron, copper, and zinc have long been associated with the aggregation of β-amyloid (Aβ) plaques in Alzheimer's disease; an interaction that has been suggested to promote increased oxidative stress and neuronal dysfunction. We examined plaque metal load in the hippocampus of APP/PS1 mice using X-ray fluorescence microscopy to assess how the anatomical location of Aβ plaques was influenced by the metal content of surrounding tissue. Immunohistochemical staining of Aβ plaques colocalized with areas of increased X-ray scattering power in unstained tissue sections, allowing direct X-ray based-assessment of plaque metal levels in sections subjected to minimal chemical fixation. We identified and mapped 48 individual plaques in four subregions of the hippocampus from four biological replicates. Iron, Cu, and Zn areal concentrations (ng cm-2) were increased in plaques compared to the surrounding neuropil. However, this elevation in metal load reflected the local metal makeup of the surrounding neuropil, where different brain regions are enriched for different metal ions. After correcting for tissue density, only Zn levels remained elevated in plaques. This study suggests that the in vivo binding of Zn to plaques is not simply due to increased protein deposition.

  17. Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization

    Science.gov (United States)

    Teng, Edmond; Taylor, Karen; Bilousova, Tina; Weiland, David; Pham, Thaidan; Zuo, Xiaohong; Yang, Fusheng; Chen, Ping-Ping; Glabe, Charles G.; Takacs, Alison; Hoffman, Dennis R.; Frautschy, Sally A.; Cole, Gregory M.

    2015-01-01

    Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer’s disease (AD). These effects have been postulated to arise from DHA’s pleiotropic effects on AD pathophysiology, including its effects on β-amyloid (Aβ) production, aggregation, and toxicity. While in vitro studies suggest DHA may inhibit and reverse the formation of toxic Aβ oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Aβ indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Aβ plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Aβ oligomer levels in the hippocampus. Further quantification of specific conformational populations of Aβ oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Aβ oligomers and decreased prefibrillar (i.e. putatively more toxic) Aβ oligomers. These results provide in vivo evidence suggesting that DHA can modulate Aβ aggregation by stabilizing soluble fibrillar Aβ oligomers and thus reduce the formation of both Aβ plaques and prefibrillar Aβ oligomers. However, since fibrillar Aβ oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Aβ oligomer levels for more effective prevention of AD in clinical settings. PMID:26369878

  18. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.

    Science.gov (United States)

    Qiu, Hongyan; Zhong, Rujia; Liu, Hui; Zhang, Feng; Li, Song; Le, Weidong

    2016-01-01

    Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPP(swe)/PS1(ΔE9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.

  19. proBDNF Accelerates Brain Amyloid-β Deposition and Learning and Memory Impairment in APPswePS1dE9 Transgenic Mice.

    Science.gov (United States)

    Chen, Jia; Zhang, Tao; Jiao, Shusheng; Zhou, Xinfu; Zhong, Jinhua; Wang, Yanjiang; Liu, Juan; Deng, Juan; Wang, Shuiping; Xu, Zhiqiang

    2017-01-01

    Alzheimer's disease (AD) is pathologically known for the amyloid-β (Aβ) deposition, neurofibrillary tangles, and neuronal loss in the brain. The precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has opposing functions to its mature form in neuronal survival and neurite growth. However, the role of proBDNF in the pathogenesis of AD remains unclear. To investigate the effects of proBDNF on neurons in vitro, and on learning and memory impairment and brain Aβ production in a transgenic AD mouse model (APPswePS1dE9). We here examined the effects of proBDNF on the viability (MTT assay) and neurite growth (morphologic measurement) of the primary neurons in vitro. After the intracerebroventricular injection of adeno-associated virus-proBDNF (AAV-proBDNF), we then investigated the learning and memory impairment (Morris water maze) and Aβ deposition in the brains of the AD mice. The results showed that proBDNF could inhibit neuronal viability and neurite growth in vitro, enhance Aβ levels, and accelerate its deposition in the brain, which was consistent with the learning and memory impairment of AD mice, likely dependent on the membrane receptor of p75NTR. Our findings suggest that proBDNF may exert a crucially negative effect during AD pathogenesis andprogression.

  20. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP+PS1 bigenic mice.

    Science.gov (United States)

    Kiyota, Tomomi; Okuyama, Satoshi; Swan, Russell J; Jacobsen, Michael T; Gendelman, Howard E; Ikezu, Tsuneya

    2010-08-01

    Cytokines play an emerging role as neurotransmitters, neuromodulators, and neurohormones in the brain. This paradigm shift in cytokine function offers a new framework to understand their roles in ameliorating neurodegenerative disorders, such as Alzheimer's disease (AD). Molecular adjuvant therapy of AD animal models with glatiramer acetate induces anti-inflammatory responses and therapeutic effects. Although these effects are potentially mediated through anti-inflammatory cytokine signaling, the exact molecular identities and pathways are poorly understood. Here, we show that virus-mediated expression of the mouse interleukin (IL)-4 gene in beta-amyloid precursor protein + presenilin-1 (APP+PS1) bigenic mice attenuates AD pathogenesis. Introduction of an adeno-associated viral (AAV) vector encoding IL-4 into the hippocampus resulted in sustained expression of IL-4, reduced astro/microgliosis, amyloid-beta peptide (Abeta) oligomerization and deposition, and enhanced neurogenesis. Moreover, increased levels of IL-4 improved spatial learning, promoted phosphorylation of N-methyl-D-aspartate receptor subunit 2B at Tyr 1472, and enhanced its cell surface retention both in vivo and in vitro. Our data suggest that neuronal anti-inflammatory cytokine signaling may be a potential alternative target for non-Abeta-mediated treatment of AD.

  1. Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe/PS1(L166P mice.

    Directory of Open Access Journals (Sweden)

    Francesca Montarolo

    Full Text Available Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe/PS1(L166P mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

  2. The reaction of fluorine atoms with methanol: yield of CH3O/CH2OH and rate constant of the reactions CH3O + CH3O and CH3O + HO2.

    Science.gov (United States)

    Assaf, Emmanuel; Schoemaecker, Coralie; Vereecken, Luc; Fittschen, Christa

    2017-11-15

    Xenondifluoride, XeF 2 , has been photolysed in the presence of methanol, CH 3 OH. Two reaction pathways are possible: F + CH 3 OH → CH 2 OH + HF and F + CH 3 OH → CH 3 O + HF. Both products, CH 2 OH and CH 3 O, will be converted to HO 2 in the presence of O 2 . The rate constants for the reaction of both radicals with O 2 differ by more than 3 orders of magnitude, which allows an unequivocal distinction between the two reactions when measuring HO 2 concentrations in the presence of different O 2 concentrations. The following yields have then been determined from time-resolved HO 2 profiles: ϕ CH 2 OH = (0.497 ± 0.013) and ϕ CH 3 O = (0.503 ± 0.013). Experiments under low O 2 concentrations lead to reaction mixtures containing nearly equal amounts of HO 2 (converted from the first reaction) and CH 3 O (from the second reaction). The subsequent HO 2 decays are very sensitive to the rate constants of the reaction between these two radicals and the following rate constants have been obtained: k(CH 3 O + CH 3 O) = (7.0 ± 1.4) × 10 -11 cm 3 s -1 and k(CH 3 O + HO 2 ) = (1.1 ± 0.2) × 10 -10 cm 3 s -1 . The latter reaction has also been theoretically investigated on the CCSD(T)//M06-2X/aug-cc-pVTZ level of theory and CH 3 OH + O 2 have been identified as the main products. Using μVTST, a virtually pressure independent rate constant of k(CH 3 O + HO 2 ) = 4.7 × 10 -11 cm 3 s -1 has been obtained, in good agreement with the experiment.

  3. Rate constant and mechanism of the reaction Cl + CFCl₂H → CFCl₂ + HCl over the temperature range 298-670 K in N₂ or N₂/O₂ diluent.

    Science.gov (United States)

    Kaiser, E W; Jawad, Khadija M

    2014-05-08

    The rate constant of the reaction Cl + CFCl2H (k1) has been measured relative to the established rate constant for the reaction Cl + CH4 (k2) at 760 Torr. The measurements were carried out in Pyrex reactors using a mixture of CFCl2H, CH4, and Cl2 in either N2 or N2/O2 diluent. Reactants and products were quantified by GC/FID analysis. Cl atoms were generated by irradiation of the mixture with 360 nm light to dissociate the Cl2 for temperatures up to ~550 K. At higher temperature, the Cl2 dissociated thermally, and no irradiation was used. Over the temperature range 298-670 K, k1 is consistently a factor of ~5 smaller than that of k2 with a nearly identical temperature dependence. The optimum non-Arrhenius rate constant is represented by the expression k1 = 1.14 × 10(-22) T(3.49) e(-241/T) cm(3) molecule(-1) s(-1) with an estimated uncertainty of ±15% including uncertainty in the reference reaction. CFCl3 formed from the reaction CFCl2 + Cl2 (k3) is the sole product in N2 diluent. In ~20% O2 at 298 K, the CFCl3 product is suppressed. The rate constant of reaction 3 was measured relative to that of reaction 4 [CFCl2 + O2 (k4)] giving the result k3/k4 = 0.0031 ± 0.0005 at 298 K. An earlier experiment by others observed C(O)FCl to be the major product of reaction channel 4 [formed via the sequence, CFCl2(O2) → CFCl2O → C(O)FCl + Cl]. Our current experiments verified that there is a Cl atom chain reaction in the presence of O2 as required by this mechanism.

  4. Electron attachment to halomethanes at high temperature: CH2Cl2, CF2Cl2, CH3Cl, and CF3Cl attachment rate constants up to 1100 K

    Science.gov (United States)

    Miller, Thomas M.; Friedman, Jeffrey F.; Schaffer, Linda C.; Viggiano, A. A.

    2009-08-01

    We have used a high-temperature flowing-afterglow Langmuir-probe apparatus to measure rate constants for electron attachment to halomethanes which attach electrons very inefficiently at room temperature, yielding Cl- ion product. We studied CH2Cl2 (495-973 K), CF2Cl2 (291-1105 K), and CF3Cl (524-1004 K) and include our recent measurement for CH3Cl (700-1100 K) in the discussion of the electron attachment results. The measured attachment rate constants show Arrhenius behavior in the temperature ranges examined, from which estimates of rate constants at 300 K may be made: CH2Cl2 (1.8×10-13 cm3 s-1), CH3Cl (1.1×10-17 cm3 s-1), and CF3Cl (4.2×10-14 cm3 s-1), all of which are difficult to measure directly. In the case of CF2Cl2, the room temperature rate constant was sufficiently large to be measured (1.6×10-9 cm3 s-1). The Arrhenius plots yield activation energies for the attachment reactions: 390±50 meV (CH2Cl2), 124±20 meV (CF2Cl2), 670±70 meV (CH3Cl), and 406±50 meV (CF3Cl). Comparisons are made with existing data where available. G3 calculations were carried out to obtain reaction energetics. They show that the parent anions of CH2Cl2 CF2Cl2, CH3Cl, and CF3Cl are stable, though CH3Cl- exists only as an electrostatically bound complex.

  5. Title: Elucidation of Environmental Fate of Artificial Sweeteners (Aspartame, Acesulfame K and Saccharin) by Determining Bimolecular Rate Constants with Hydroxyl Radical at Various pH and Temperature Conditions and Possible Reaction By-Products

    Science.gov (United States)

    Teraji, T.; Arakaki, T.; Suzuka, T.

    2012-12-01

    Use of artificial sweeteners in beverages and food has been rapidly increasing because of their non-calorie nature. In Japan, aspartame, acesulfame K and sucralose are among the most widely used artificial sweeteners. Because the artificial sweeteners are not metabolized in human bodies, they are directly excreted into the environment without chemical transformations. We initiated a study to better understand the fate of artificial sweeteners in the marine environment. The hydroxyl radical (OH), the most potent reactive oxygen species, reacts with various compounds and determines the environmental oxidation capacity and the life-time of many compounds. The steady-state OH concentration and the reaction rate constants between the compound and OH are used to estimate the life-time of the compound. In this study, we determine the bimolecular rate constants between aspartame, acefulfame K and saccharin and OH at various pH and temperature conditions using a competition kinetics technique. We use hydrogen peroxide as a photochemical source of OH. Bimolecular rate constant we obtained so far for aspartame was (2.6±1.2)×109 M-1 s-1 at pH = 3.0 and (4.9±2.3)×109 M-1 s-1 at pH = 5.5. Little effect was seen by changing the temperatures between 15 and 40 oC. Activation energy (Ea) was calculated to be -1.0 kJ mol-1 at pH = 3.0, +8.5 kJ mol-1 at pH = 5.5, which could be regarded as zero. We will report bimolecular rate constants at different pHs and temperatures for acesulfame K and saccharin, as well. Possible reaction by-products for aspartame will be also reported. We will further discuss the fate of aspartame in the coastal environment.

  6. Rate constants of the equilibrium reactions SO⨪4 + HNO3 ⇄ HSO-4 + NO3 and SO⨪4 + NO-3 ⇄ SO2-4 + NO3

    DEFF Research Database (Denmark)

    Løgager, T.; Sehested, K.; Holcman, J.

    1993-01-01

    Rate constants of the following equilibrium reactions were determined by pulse radiolysis at high solute concentrations: SO4.- + HNO, half arrow right over half arrow left HSO4- + NO3. [k(f) = (2.7 +/- 0.5) x 10(6) M-1 s-1, k(r) = (5.6 +/- 1.0) x 10(3) M-1 s-1] and SO4.- + NO3- half arrow right...

  7. Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer?s disease

    OpenAIRE

    HAN, KUN; JIA, NING; LI, JI; YANG, LI; MIN, LIAN-QIU

    2013-01-01

    The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the ...

  8. Oxygenation, local muscle oxygen consumption and joint specific power in cycling: the effect of cadence at a constant external work rate.

    Science.gov (United States)

    Skovereng, Knut; Ettema, Gertjan; van Beekvelt, Mireille C P

    2016-06-01

    The present study investigates the effect of cadence on joint specific power and oxygenation and local muscle oxygen consumption in the vastus lateralis and vastus medialis in addition to the relationship between joint specific power and local muscle oxygen consumption (mVO2). Seventeen recreationally active cyclists performed 6 stages of constant load cycling using cadences of 60, 70, 80, 90, 100 and 110 rpm. Joint specific power was calculated using inverse dynamics and mVO2 and oxygenation were measured using near-infrared spectroscopy. Increasing cadence led to increased knee joint power and decreased hip joint power while the ankle joint was unaffected. Increasing cadence also led to an increased deoxygenation in both the vastus lateralis and vastus medialis. Vastus lateralis mVO2 increased when cadence was increased. No effect of cadence was found for vastus medialis mVO2. This study demonstrates a different effect of cadence on the mVO2 of the vastus lateralis and vastus medialis. The combined mVO2 of the vastus lateralis and medialis showed a linear increase with increasing knee joint specific power, demonstrating that the muscles combined related to power generated over the joint.

  9. 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.

    Science.gov (United States)

    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.

  10. Analysis of initial chlorophyll fluorescence induction kinetics in chloroplasts in terms of rate constants of donor side quenching release and electron trapping in photosystem II

    NARCIS (Netherlands)

    Vredenberg, W.J.

    2008-01-01

    The fluorescence induction F(t) of dark-adapted chloroplasts has been studied in multi-turnover 1 s light flashes (MTFs). A theoretical expression for the initial fluorescence rise is derived from a set of rate equations that describes the sequence of transfer steps associated with the reduction of

  11. Hydrolysis rate constants at 10–25 °C can be more than doubled by a short anaerobic pre-hydrolysis at 35 °C

    NARCIS (Netherlands)

    Zhang, L.; Gao, R.; Naka, A.; Hendrickx, T.L.G.; Rijnaarts, H.H.M.; Zeeman, G.

    2016-01-01

    Hydrolysis is the first step of the anaerobic digestion of complex wastewater and considered as the rate limiting step especially at low temperature. Low temperature (10–25 °C) hydrolysis was investigated with and without application of a short pre-hydrolysis at 35 °C. Batch experiments were

  12. DETERMINATION OF RATE CONSTANT AND STABILITY OF ADSORPTION IN COMPETITIVE ADSORPTION OF Cr(III AND Cd(II ON HUMIC ACID BY USING THE NEW MODEL OF KINETIC FORMULATION

    Directory of Open Access Journals (Sweden)

    Suyanta Suyanta

    2010-06-01

    Full Text Available Determination of rate and stability constants of adsorption in competitive adsorption of Cr(III and Cd(II on humic acid by using the new model of kinetic formulation has been done. The new model based on assumption that those adsorption was first order adsorption rearched equilibrium. Humic acid was isolated from Peat moss of Silaut- West Sumatra by modificated Schnitzer method. Humic acid characterization was conducted by using infrared spectrophotometer with KBR pellet method. The experiment of kinetic adsorption was conducted in batch system reactor using erlenmeyer at 25 ± 0.01 oC of water steam bath and in a series of sampling procedure. Initial concentration of both Cr(III and Cd(II was 4x10-4 M. Thirty milligrams of humic acid was added to 200 mL of metal solution, and then stirred continuously. At the fixed periode of time, 10 mL of sample was taken using a syringe, then filterd with 0.45 µm filter paper. Concentration of Cr(III and Cd(II in the filtrate was determinated by AAS, while that was adsorbed by humic acid was equal to difference between initial and equilibrium concentration. It was concluded that competitive adsorption of Cr(III and Cd(II on humic acid was first order adsorption rearched equilibrium as proposed in this research. Adsorption rate constant of Cr(III on humic acid  at competitive condition was greater than of Cd(II, but on the contrary for stability constant (K. Competition between Cr(III and Cd(II to interact with the active side of humic acid was dominated by Cr(III.   Keywords: rate constant, stability and competitive adsorption

  13. Flash photolytic generation and study of p-quinone methide in aqueous solution. An estimate of rate and equilibrium constants for heterolysis of the carbon-bromine bond in p-hydroxybenzyl bromide.

    Science.gov (United States)

    Chiang, Y; Kresge, A J; Zhu, Y

    2002-06-05

    Flash photolysis of p-hydroxybenzyl acetate in aqueous perchloric acid solution and formic acid, acetic acid, biphosphate ion, and tris(hydroxymethyl)methylammonium ion buffers produced p-quinone methide as a short-lived species that underwent hydration to p-hydroxybenzyl alcohol in hydronium ion catalyzed (k(H(+)) = 5.28 x 10(4) M(-1) s(-1)) and uncatalyzed (k(uc) = 3.33 s(-1)) processes. The inverse nature of the solvent isotope effect on the hydronium ion-catalyzed reaction, k(H(+))/k(D(+)) = 0.41, indicates that this process occurs by rapid and reversible protonation of the quinone methide on its carbonyl carbon atom, followed by rate-determining capture of the p-hydroxybenzyl carbocation so produced by water, while the magnitude of the rate constant on the uncatalyzed process indicates that this reaction occurs by simple nucleophilic addition of water to the methylene group of the quinone methide. p-Quinone methide also underwent hydronium ion-catalyzed and uncatalyzed nucleophilic addition reactions with chloride ion, bromide ion, thiocyanate ion, and thiourea. The solvent isotope effects on the hydronium ion-catalyzed processes again indicate that these reactions occurred by preequilibrium mechanisms involving a p-hydroxybenzyl carbocation intermediate, and assignment of a diffusion-controlled value to the rate constant for reaction of this cation with thiocyanate ion led to K(SH) = 110 M as the acidity constant of oxygen-protonated p-quinone methide. In a certain perchloric acid concentration range, the bromide ion reaction became biphasic, and least-squares analysis of the kinetic data using a double-exponential function provided k(Br(-)) = 3.8 x 10(8) M(-1) s(-1) as the rate constant for nucleophilic capture of the p-hydroxybenzyl carbocation by bromide ion, k(ionz) = 8.5 x 10(2) s(-1) for ionization of the carbon-bromine bond of p-hydroxybenzyl bromide, and K = 4.5 x 10(5) M(-1) as the equilibrium constant for the carbocation-bromide ion combination

  14. Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer's disease is impaired in old but not young mice.

    Directory of Open Access Journals (Sweden)

    Simon Gengler

    Full Text Available BACKGROUND: Alzheimer disease (AD is a neurodegenerative disorder for which there is no cure. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21 which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays beta-amyloid-associated pathologies and learning impairments. METHODOLOGY/PRINCIPAL FINDINGS: We tested long-term potentiation (LTP and short term potentiation (paired-pulse facilitation, PPF of synaptic transmission in vivo in area CA1 of the hippocampus. There was no difference in LTP or PPF at 4-5 months of age in APPPS1-21 mice compared to littermate controls. At 6 months of age there was also no difference in LTP but APPPS1-21 mice showed slightly increased PPF (p<0.03. In 8 months old mice, LTP was greatly impaired in APPPS-21 animals (p<0.0001 while PPF was not changed. At 15 months of age, APPPS1-21 mice showed again impaired LTP compared to littermate controls (p<0.005, and PPF was also significantly reduced at 80 ms (p<0.005 and 160 ms (p<0.01 interstimulus interval. Immunohistological analysis showed only modest amyloid deposition in the hippocampus at 4 and 6 months with a robust increase up to 15 months of age. CONCLUSIONS: Our results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired LTP with aging in this mouse model, while the transient increase of PPF at 6 months of age is caused by some other mechanism.

  15. Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575

    Directory of Open Access Journals (Sweden)

    Golde Todd E

    2009-05-01

    Full Text Available Abstract The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology.

  16. Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe ×PS1Δe9 transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Chaney, Aisling; Bauer, Martin; Bochicchio, Daniela; Smigova, Alison; Kassiou, Michael; Davies, Karen E; Williams, Steve R; Boutin, Herve

    2018-02-01

    There is increasing evidence linking neuroinflammation to many neurological disorders including Alzheimer's disease (AD); however, its exact contribution to disease manifestation and/or progression is poorly understood. Therefore, there is a need to investigate neuroinflammation in both health and disease. Here, we investigate cognitive decline, neuroinflammatory and other pathophysiological changes in the APPswe ×PS1Δe9 transgenic mouse model of AD. Transgenic (TG) mice were compared to C57BL/6 wild type (WT) mice at 6, 12 and 18 months of age. Neuroinflammation was investigated by [18 F]DPA-714 positron emission tomography and myo-inositol levels using 1 H magnetic resonance spectroscopy (MRS) in vivo. Neuronal and cellular dysfunction was investigated by looking at N-acetylaspartate (NAA), choline-containing compounds, taurine and glutamate also using MRS. Cognitive decline was first observed at 12 m of age in the TG mice as assessed by working memory tests . A significant increase in [18 F]DPA-714 uptake was seen in the hippocampus and cortex of 18 m-old TG mice when compared to age-matched WT mice and 6 m-old TG mice. No overall effect of gene was seen on metabolite levels; however, a significant reduction in NAA was observed in 18 m-old TG mice when compared to WT. In addition, age resulted in a decrease in glutamate and an increase in choline levels. Therefore, we can conclude that increased neuroinflammation and cognitive decline are observed in TG animals, whereas NAA alterations occurring with age are exacerbated in the TG mice. These results support the role of neuroinflammation and metabolite alteration in AD and in ageing. © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  17. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    Science.gov (United States)

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  18. Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Yue Yang

    Full Text Available Alzheimer's disease (AD is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ in brain and retina. Because bone marrow transplantation (BMT results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Aβ and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Aβ and paired helical filament-tau were reduced (61.0% and 44.1% respectively in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4% compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice.

  19. AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer’s Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons

    Directory of Open Access Journals (Sweden)

    Feng-li Zhao

    2016-01-01

    Full Text Available Increasing evidence suggests that mitochondrial functions are altered in AD and play an important role in AD pathogenesis. It has been established that H2S homeostasis is balanced in AD. The emerging mitochondrial roles of H2S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well-characterized APP/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H2S donor on mitochondrial function. AP39 increased intracellular H2S levels, mainly in mitochondrial regions. AP39 exerted dose-dependent effects on mitochondrial activity in APP/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25–100 nM and decreased energy production and cell viability at a high concentration (250 nM. Furthermore, AP39 (100 nM increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced Aβ deposition in their brains. Additionally, AP39 inhibited brain atrophy in APP/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti-AD mechanism may involve protection against mitochondrial damage.

  20. AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer's Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons.

    Science.gov (United States)

    Zhao, Feng-Li; Fang, Fang; Qiao, Pei-feng; Yan, Ning; Gao, Dan; Yan, Yong

    2016-01-01

    Increasing evidence suggests that mitochondrial functions are altered in AD and play an important role in AD pathogenesis. It has been established that H2S homeostasis is balanced in AD. The emerging mitochondrial roles of H2S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well-characterized APP/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H2S donor) on mitochondrial function. AP39 increased intracellular H2S levels, mainly in mitochondrial regions. AP39 exerted dose-dependent effects on mitochondrial activity in APP/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25-100 nM) and decreased energy production and cell viability at a high concentration (250 nM). Furthermore, AP39 (100 nM) increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced Aβ deposition in their brains. Additionally, AP39 inhibited brain atrophy in APP/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti-AD mechanism may involve protection against mitochondrial damage.

  1. Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer’s disease

    Science.gov (United States)

    HAN, KUN; JIA, NING; LI, JI; YANG, LI; MIN, LIAN-QIU

    2013-01-01

    The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process. PMID:23900282

  2. Cosmological constant, fine structure constant and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Hao; Zou, Xiao-Bo; Li, Hong-Yu; Xue, Dong-Ze [Beijing Institute of Technology, School of Physics, Beijing (China)

    2017-01-15

    In the present work, we consider the cosmological constant model Λ ∝ α{sup -6}, which is well motivated from three independent approaches. As is well known, the hint of varying fine structure constant α was found in 1998. If Λ ∝ α{sup -6} is right, it means that the cosmological constant Λ should also be varying. Here, we try to develop a suitable framework to model this varying cosmological constant Λ ∝ α{sup -6}, in which we view it from an interacting vacuum energy perspective. Then we consider the observational constraints on these models by using the 293 Δα/α data from the absorption systems in the spectra of distant quasars. We find that the model parameters can be tightly constrained to the very narrow ranges of O(10{sup -5}) typically. On the other hand, we can also view the varying cosmological constant model Λ ∝ α{sup -6} from another perspective, namely it can be equivalent to a model containing ''dark energy'' and ''warm dark matter'', but there is no interaction between them. We find that this is also fully consistent with the observational constraints on warm dark matter. (orig.)

  3. An early dysregulation of FAK and MEK/ERK signaling pathways precedes the β-amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Lachén-Montes, Mercedes; González-Morales, Andrea; de Morentin, Xabier Martínez; Pérez-Valderrama, Estela; Ausín, Karina; Zelaya, María Victoria; Serna, Antonio; Aso, Ester; Ferrer, Isidro; Fernández-Irigoyen, Joaquín; Santamaría, Enrique

    2016-10-04

    Olfactory dysfunction is an early event of Alzheimer's disease (AD). However, the mechanisms associated to AD neurodegeneration in olfactory areas are unknown. Here we used double-transgenic amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) mice and label-free quantitative proteomics to analyze early pathological effects on the olfactory bulb (OB) during AD progression. Prior to β-amyloid plaque formation, 9 modulated proteins were detected on 3-month-old APP/PS1 mice while 16 differential expressed proteins were detected at 6months, when β-amyloid plaques appear, indicating a moderate imbalance in cytoskeletal rearrangement, and synaptic plasticity in APP/PS1 OBs. Moreover, β-amyloid induced an inactivation of focal adhesion kinase (FAK) together with a transient activation of MEK1/2, leading to inactivation of ERK1/2 in 6-months APP/PS1 OBs. In contrast, the analysis of human OBs revealed a late activation of FAK in advanced AD stages, whereas ERK1/2 activation was enhanced across AD staging respect to controls. This survival potential was accompanied by the inhibition of the proapototic factor BAD in the OB across AD phenotypes. Our data contribute to a better understanding of the early molecular mechanisms that are modulated in AD neurodegeneration, highlighting significant differences in the regulation of survival pathways between APP/PS1 mice and sporadic human AD. Loss of smell is involved in early stages of Alzheimer's disease (AD), usually preceding classic disease symptoms. However, the mechanisms governing this dysfunction are still poorly understood, losing its potential as a useful tool for clinical diagnosis. Our study characterizes potential AD-associated molecular changes in APP/PS1 mice olfactory bulb (OB) using MS-quantitative proteomics, revealing early cytoskeletal disruption and synaptic plasticity impairment. Moreover, an opposite pattern was found when comparing the activation status of specific survival pathways between APP/PS1 OBs

  4. Ion exchange equilibrium constants

    CERN Document Server

    Marcus, Y

    2013-01-01

    Ion Exchange Equilibrium Constants focuses on the test-compilation of equilibrium constants for ion exchange reactions. The book first underscores the scope of the compilation, equilibrium constants, symbols used, and arrangement of the table. The manuscript then presents the table of equilibrium constants, including polystyrene sulfonate cation exchanger, polyacrylate cation exchanger, polymethacrylate cation exchanger, polysterene phosphate cation exchanger, and zirconium phosphate cation exchanger. The text highlights zirconium oxide anion exchanger, zeolite type 13Y cation exchanger, and

  5. Cheap but accurate calculation of chemical reaction rate constants from ab initio data, via system-specific, black-box force fields.

    Science.gov (United States)

    Steffen, Julien; Hartke, Bernd

    2017-10-28

    Building on the recently published quantum-mechanically derived force field (QMDFF) and its empirical valence bond extension, EVB-QMDFF, it is now possible to generate a reliable potential energy surface for any given elementary reaction step in an essentially black box manner. This requires a limited and pre-defined set of reference data near the reaction path and generates an accurate approximation of the reference potential energy surface, on and off the reaction path. This intermediate representation can be used to generate reaction rate data, with far better accuracy and reliability than with traditional approaches based on transition state theory (TST) or variational extensions thereof (VTST), even if those include sophisticated tunneling corrections. However, the additional expense at the reference level remains very modest. We demonstrate all this for three arbitrarily chosen example reactions.

  6. Cheap but accurate calculation of chemical reaction rate constants from ab initio data, via system-specific, black-box force fields

    Science.gov (United States)

    Steffen, Julien; Hartke, Bernd

    2017-10-01

    Building on the recently published quantum-mechanically derived force field (QMDFF) and its empirical valence bond extension, EVB-QMDFF, it is now possible to generate a reliable potential energy surface for any given elementary reaction step in an essentially black box manner. This requires a limited and pre-defined set of reference data near the reaction path and generates an accurate approximation of the reference potential energy surface, on and off the reaction path. This intermediate representation can be used to generate reaction rate data, with far better accuracy and reliability than with traditional approaches based on transition state theory (TST) or variational extensions thereof (VTST), even if those include sophisticated tunneling corrections. However, the additional expense at the reference level remains very modest. We demonstrate all this for three arbitrarily chosen example reactions.

  7. Direct measurements of rate constants for the reactions of CH3 radicals with C2H6, C2H4, and C2H2 at high temperatures.

    Science.gov (United States)

    Peukert, S L; Labbe, N J; Sivaramakrishnan, R; Michael, J V

    2013-10-10

    The shock tube technique has b