Repeated challenge with prion disease: The risk of infection and impact on incubation period

Natural exposure to prion disease is likely to occur throughout successive challenges, yet most experiments focus on single large doses of infectious material. We analyze the results from an experiment in which rodents were exposed to multiple doses of feed contaminated with the scrapie agent. We formally define hypotheses for how the doses combine in terms of statistical models. The competing hypotheses are that only the total dose of infectivity is important (cumulative model), doses act independently, or a general alternative that interaction between successive doses occurs (to raise or lower the risk of infection). We provide sample size calculations to distinguish these hypotheses. In the experiment, a fixed total dose has a significantly reduced probability of causing infection if the material is presented as multiple challenges, and as the time between challenges lengthens. Incubation periods are shorter and less variable if all material is consumed on one occasion. We show that the probability of infection is inconsistent with the hypothesis that each dose acts as a cumulative or independent challenge. The incubation periods are inconsistent with the independence hypothesis. Thus, although a trend exists for the risk of infection with prion disease to increase with repeated doses, it does so to a lesser degree than is expected if challenges combine independently or in a cumulative manner.

A temperature-dependent relative-rate study of the OH initiated oxidation of n-butane: the kinetics of the reactions of the 1-and 2-butoxy radicals

The kinetics of the reactions of 1-and 2-butoxy radicals have been studied using a slow-flow photochemical reactor with GC-FID detection of reactants and products. Branching ratios between decomposition, CH3CH(O-.)CH2CH3 CH3CHO + C2H5, reaction (7), and reaction with oxygen, CH3CH(O-.)CH2CH3 + O-2 -> CH3C(O)C2H5 + HO2, reaction (6), for the 2-butoxy radical and between isomerization, CH3CH2CH2CH2O. -> CH2CH2CH2CH2OH, reaction (9), and reaction with oxygen, CH3CH2CH2CH2O. + O-2 -> C3H7CHO + HO2, reaction (8), for the 1-butoxy radical were measured as a function of oxygen concentration at atmospheric pressure over the temperature range 250-318 K. Evidence for the formation of a small fraction of chemically activated alkoxy radicals generated from the photolysis of alkyl nitrite precursors and from the exothermic reaction of 2-butyl peroxy radicals with NO was observed. The temperature dependence of the rate constant ratios for a thermalized system is given by k(7)/k(6) = 5.4 x 1026 exp[(-47.4 +/- 2.8 kJ mol(-1))/RT] molecule cm(-3) and k(9)/k(8) = 1.98 x 10(23) exp[(-22.6 +/- 3.9 kJ mol(-1))/RT] molecule cm(-3). The results agree well with the available experimental literature data at ambient temperature but the temperature dependence of the rate constant ratios is weaker than in current recommendations.

The kinetics of the 2π+2π photodimerisation reactions of single-crystalline derivatives of trans-cinnamic acid: a study by infrared microspectroscopy

The kinetics of the photodimerisation reactions of the 2- and 4-β-halogeno-derivatives of trans-cinnamic acid (where the halogen is fluorine, chlorine or bromine) have been investigated by infrared microspectroscopy. It is found that none of the reactions proceed to 100% yield. This is in line with a reaction mechanism developed by Wernick and his co-workers that postulates the formation of isolated monomers within the solid, which cannot react. β-4-Bromo and β-4-chloro-trans-cinnamic acids show approximately first order kinetics, although in both cases the reaction accelerates somewhat as it proceeds. First order kinetics is explained in terms of a reaction between one excited- and one ground-state monomer molecule, while the acceleration of the reaction implies that it is promoted as defects are formed within the crystal. By contrast β-2-chloro-trans-cinnamic acid shows a strongly accelerating reaction which models closely to the contracting cube equation. β-2-Fluoro- and β-4-fluoro-trans-cinnamic acids show a close match to first order kinetics. The 4-fluoro-derivative, however, shows a reaction that proceeds via a structural intermediate. The difference in behaviour between the 2-fluoro- and 4-fluoro-derivative may be due to different C–HF hydrogen bonds observed within these single-crystalline starting materials.

The kinetics of the gas-phase decomposition of the 2-methyl-2-butoxyl and 2-methyl-2-pentoxyl radicals

The kinetics of the title reactions have been studied by relative-rate methods as a function of temperature. Relative-rate coefficients for the two decomposition channels of 2-methyl-2-butoxyl have been measured at five different temperatures between 283 and 345 K and the observed temperature dependence is consistent with the results of some previous experimental studies. The kinetics of the two decomposition channels of 2-methyl-2-pentoxyl have also been investigated, as a function of temperature, relative to the estimated rate of isomerisation of this radical. Room-temperature rate coefficient data for the two decomposition channels of both 2-methyl-2-pentoxyl and 2-methyl-2-butxoyl (after combining the relative rate coefficient for this latter with a value for the rate coefficient of the major channel, extrapolated from the data presented by Batt et al., Int. J. Chem. Kinet., 1978, 10, 931) are shown to be consistent with a non-linear kinetic correlation, for alkoxyl radical decomposition rate data, previously presented by this laboratory (Johnson et al., Atmos. Environ., 2004, 38, 1755-1765).

Correlation-type structure activity relationships for the kinetics of gas-phase RO2 self-reactions and reaction with HO2

Structure activity relationships (SARs) are presented for the gas-phase reactions of RO2 with HO2, and the self- and cross-reactions of RO2. For RO2+HO2 the SAR is based upon a correlation between the logarithm of the measured rate coefficient and a calculated ionisation potential for the molecule R-CH=CH2, R being the same group in both the radical and molecular analogue. The correlation observed is strong and only for one RO2 species does the measured rate coefficient deviate by more than a factor of two from the linear least-squares regression line. For the self- and cross-reactions of RO2 radicals, the SAR is based upon a correlation between the logarithm of the measured rate coefficient and the calculated electrostatic potential (ESP) at the equivalent carbon atom in the RH molecule to which oxygen is attached in RO2, again R being the same group in the molecule and the radical. For cases where R is a simple alkyl-group, a strong linear correlation observed. For RO2 radicals which contain lone pair-bearing substituents and for which the calculated ESP<-0.05 self-reaction rate coefficients appear to be insensitive to the value of the ESP. For RO2 of this type with ESP>-0.05 a linear relationship between log k and the ESP is again observed. Using the relationships, 84 out of the 85 rate coefficients used to develop the SARs are predicted to within a factor of three of their measured values. A relationship is also presented that allows the prediction of the Arrhenius parameters for the self-reactions of simple alkyl RO2 radicals. On the basis of the correlations, predictions of room-temperature rate coefficients are made for a number of atmospherically important peroxyl-peroxyl radical reactions. (C) 2003 Elsevier Ltd. All rights reserved.

Self-nucleation and crystallization kinetics of double crystalline poly(p-dioxanone)-b-poly(epsilon-caprolactone) diblock copolymers

The crystallization kinetics of each constituent of poly(p-dioxanone)-b-poly(epsilon-caprolactone) diblock copolymers (PPDX-b-PCL) has been determined in a wide composition range by differential scanning calorimetry and compared to that of the equivalent homopolymers. Spherulitic growth rates were also measured by polarized optical microscopy while atomic force microscopy was employed to reveal the morphology of one selected diblock copolymer. It was found that crystallization drives structure formation and both components form lamellae within mixed spherulitic superstructures. The overall isothermal crystallization kinetics of the PPDX block at high temperatures, where the PCL is molten, was determined by accelerating the kinetics through a previous self-nucleation procedure. The application of the Lauritzen and Ho. man theory to overall growth rate data yielded successful results for PPDX and the diblock copolymers. The theory was applied to isothermal overall crystallization of previously self-nucleated PPDX ( where growth should be the dominant factor if self-nucleation was effective) and the energetic parameters obtained were perfectly matched with those obtained from spherulitic growth rate data of neat PPDX. A quantitative estimate of the increase in the energy barrier for crystallization of the PPDX block, caused by the covalently bonded molten PCL as compared to homo-PPDX, was thus determined. This energy increase can dramatically reduce the crystallization rate of the PPDX block as compared to homo-PPDX. In the case of the PCL block, both the crystallization kinetics and the self-nucleation results indicate that the PPDX is able to nucleate the PCL within the copolymers and heterogeneous nucleation is always present regardless of composition. Finally, preliminary results on hydrolytic degradation showed that the presence of relatively small amounts of PCL within PPDX-bPCL copolymers substantially retards hydrolytic degradation of the material in comparison to homo-PPDX. This increased resistance to hydrolysis is a complex function of composition and its knowledge may allow future prediction of the lifetime of the material for biomedical applications.

Quantitative model for the kinetics of lyotropic phase transitions involving changes in monolayer curvature

We present a kinetic model for transformations between different self-assembled lipid structures. The model shows how data on the rates of phase transitions between mesophases of different geometries can be used to provide information on the mechanisms of the transformations and the transition states involved. This can be used, for example, to gain an insight into intermediate structures in cell membrane fission or fusion. In cases where the monolayer curvature changes on going from the initial to the final mesophase, we consider the phase transition to be driven primarily by the change in the relaxed curvature with pressure or temperature, which alters the relative curvature elastic energies of the two mesophase structures. Using this model, we have analyzed previously published kinetic data on the inter-conversion of inverse bicontinuous cubic phases in the 1-monoolein-30 wt% water system. The data are for a transition between QII(G) and QII(D) phases, and our analysis indicates that the transition state more closely resembles the QII(D) than the QII(G) phase. Using estimated values for the monolayer mean curvatures of the QII(G) and QII(D) phases of -0.123 nm(-1) and -0.133 nm(-1), respectively, gives values for the monolayer mean curvature of the transition state of between -0.131 nm(-1) and -0.132 nm(-1). Furthermore, we estimate that several thousand molecules undergo the phase transition cooperatively within one "cooperative unit", equivalent to 1-2 unit cells of QII(G) or 4-10 unit cells of QII(D).

Modelling the uptake and growth kinetics of Penicillium glabrum in a tannic acid-containing solid-state fermentation for tannase production

A mathematical growth model for the batch solid-state fermentation process for fungal tannase production was developed and tested experimentally. The unstructured model describes the uptake and growth kinetics of Penicillium glabrum in an impregnated polyurethane foam substrate system. In general, good agreement between the experimental data and model simulations was obtained. Biomass, tannase and spore production are described by logistic kinetics with a time delay between biomass production and tannase and spore formation. Possible induction mechanisms for the latter are proposed. Hydrolysis of tannic acid, the main carbon source in the substrate system, is reasonably well described with Michaelis-Menten kinetics with time-varying enzyme concentration but a more complex reaction mechanism is suspected. The metabolism of gallic acid, a tannase-hydrolysis product of tannic acid, was shown to be growth limiting during the main growth phase. (c) 2004 Elsevier Ltd. All rights reserved.

Kinetics of high pressure facilitated starch gelatinisation in Thai glutinous rice

The combined effect of pressure and temperature on the rate of gelatinisation of starch present in Thai glutinous rice was investigated. Pressure was found to initiate gelatinisation when its value exceeded 200 MPa at ambient temperature. On the other hand, complete gelatinisation was observed at 500 and 600 MPa at 70 degrees C, when the rice was soaked in water under these conditions for 120 min. A first-order kinetic model describing the rate of gelatinisation was developed to estimate the values of the rate constants as a function of pressure and temperature in the range: 0.1-600 MPa and 20-70 degrees C. The model, based on the well-known Arrhenius and Eyring equations, assumed the form [GRAPHICS] The constants k(0), E-a, and Delta V were found to take values: 31.19 s(-1), 37.89 kJ mol(-1) and -9.98 cm(3) mol(-1), respectively. It was further noted that the extent of gelatinisation occurring at any time, temperature and pressure, could be exclusively correlated with the grain moisture content. (c) 2006 Elsevier Ltd. All rights reserved.

Gas-phase kinetics of chlorosilylene reactions II. ClSiH + C2H4: absolute rate measurements and quantum chemical and RRKM calculations for the prototype pi addition reaction

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, are carried out to obtain rate constants for its bimolecular reaction with ethene, C2H4, in the gas-phase. The reaction is studied over the pressure range 0.13-13.3 kPa (with added SF6) at five temperatures in the range 296-562 K. The second order rate constants, obtained by extrapolation to the high pressure limits at each temperature, fitted the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1))=(-10.55 +/- 0.10) + (3.86 +/- 0.70) kJ mol(-1)/RT ln10. The Arrhenius parameters correspond to a loose transition state and the rate constant at room temperature is 43% of that for SiH2 + C2H4, showing that the deactivating effect of Cl-for-H substitution in the silylene is not large. Quantum chemical calculations of the potential energy surface for this reaction at the G3MP2//B3LYP level show that, as well as 1-chlorosilirane, ethylchlorosilylene is a viable product. The calculations reveal how the added effect of the Cl atom on the divalent state stabilisation of ClSiH influences the course of this reaction. RRKM calculations of the reaction pressure dependence suggest that ethylchlorosilylene should be the main product. The results are compared and contrasted with those of SiH2 and SiCl2 with C2H4.

Gas-phase kinetics of chlorosilylene reactions. I. ClSiH + Me3SiH: absolute rate measurements and theoretical calculations for prototype Si−H insertion reactions

Time-resolved studies of chlorosilylene, CISiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reaction with trimethylsilane, Me3SiH, in the gas phase. The reaction was studied at total pressures up to 100 torr (with and without added SF6) over the temperature range 297-407 K. The rate constants were found to be pressure independent and gave the following Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-13.97 +/- 0.25) + (12.57 +/- 1.64) kJ mol(-1)/RT In 10. The Arrhenius parameters are consistent with a mechanism involving an intermediate complex, whose rearrangement is the rate-determining step. Quantum chemical calculations of the potential energy surface for this reaction and also the reactions of CISiH with SiH4 and the other methylsilanes support this conclusion. Comparisons of both experiment and theory with the analogous Si-H insertion processes of SiH2 and SiMe2 show that the main factor causing the lower reactivity of ClSiH is the secondary energy barrier. The calculations also show the existence of a novel intramolecular H-atom exchange process in the complex of ClSiH with MeSiH3.

Direct time-resolved study of the kinetics of the reaction of silylene with phenylsilane in the gas phase. Does SiH2 react with the aromatic ring?

Laser flash photolysis studies of silylene, SiH2, generated by the 193 nm laser flash photolysis phenylsilane, PhSiH3, have been carried out to obtain rate constants for its bimolecular reaction with PhSiH3 itself, in the gas phase. The reaction was studied in SF6 (mostly at 10 Torr total pressure) over the temperature range 298-595 K. The rate constants (also found to be pressure independent) gave the following Arrhenius equation: log(k/cm(3) molecule(-1) s(-1)) = (-9.92 +/- 0.04) + (3.31 +/- 0.27) kJ mol(-1)/RT ln 10 Similar investigations of the reaction of silylene with benzene, C6H6, (295-410 K) gave data suggestive of the fact that SiH2 might be reacting with photochemical products of C6H6 as well as with C6H6 itself. However, in the latter system, apparent rate constants were sufficiently low to indicate that in the reaction of SiH2 with PhSiH3 addition to the aromatic ring was unlikely to be in excess of 3% of the total. Quantum chemical calculations of the energy surface for SiH2 + C6H6 indicate that 7-silanorcaradiene and 7-silacycloheptatriene are possible products but that PhSiH3 formation is unlikely. RRKM calculations suggest that 7-silanorcaradiene should be the initial product but that it cannot be collisionally stabilized under experimental conditions

Kinetics of layer hopping in a diblock copolymer lamellar phase

In the ordered state, symmetric diblock copolymers self-assemble into an anisotropic lamellar morphology. The equilibrium thickness of the lamellae is the result of a delicate balance between enthalpic and entropic energies, which can be tuned by controlling the temperature. Here we devise a simple yet powerful method of detecting tiny changes in the lamellar thickness using optical microscopy. From such measurements we characterize the enthalpic interaction as well as the kinetics of molecules as they hop from one layer to the next in order to adjust the lamellar thickness in response to a temperature jump. The resolution of the measurements facilitate a direct comparison to predictions from self-consistent field theory.

Kinetics of the reaction between OH radicals and monochlorodimethylsulphide (CH3SCH2Cl)

The gas-phase rate coefficient for the reaction between OH radicals and CH3SCH2Cl (MCDMS) was determined to be (2.5±1.3)×10−12 cm3 molecule−1 s−1 using the discharge–flow kinetic technique. An estimate of ≈10−10 cm3 molecule−1 s−1 was obtained for the rate coefficient for reaction of Cl with MCDMS. It would appear that the reaction with OH is not the main loss process for CH3SCH2Cl in the marine boundary layer. The possible implications for the MBL of halogen-promoted oxidation of dimethylsulphide are considered.

Determination of the degradation kinetics of anthocyanins in a model juice system using isothermal and non-isothermal methods

The effect of temperature on the degradation of blackcurrant anthocyanins in a model juice system was determined over a temperature range of 4–140 °C. The thermal degradation of anthocyanins followed pseudo first-order kinetics. From 4–100 °C an isothermal method was used to determine the kinetic parameters. In order to mimic the temperature profile in retort systems, a non-isothermal method was applied to determine the kinetic parameters in the model juice over the temperature range 110–140 °C. The results from both isothermal and non-isothermal methods fit well together, indicating that the non-isothermal procedure is a reliable mathematical method to determine the kinetics of anthocyanin degradation. The reaction rate constant (k) increased from 0.16 (±0.01) × 10−3 to 9.954 (±0.004) h−1 at 4 and 140 °C, respectively. The temperature dependence of the rate of anthocyanin degradation was modelled by an extension of the Arrhenius equation, which showed a linear increase in the activation energy with temperature.