A modified discrete random pore model allowing for different initial surface reactivity

We investigate here a modification of the discrete random pore model [Bhatia SK, Vartak BJ, Carbon 1996;34:1383], by including an additional rate constant which takes into account the different reactivity of the initial pore surface having attached functional groups and hydrogens, relative to the subsequently exposed surface. It is observed that the relative initial reactivity has a significant effect on the conversion and structural evolution, underscoring the importance of initial surface chemistry. The model is tested against experimental data on chemically controlled char oxidation and steam gasification at various temperatures. It is seen that the variations of the reaction rate and surface area with conversion are better represented by the present approach than earlier random pore models. The results clearly indicate the improvement of model predictions in the low conversion region, where the effect of the initially attached functional groups and hydrogens is more significant, particularly for char oxidation. It is also seen that, for the data examined, the initial surface chemistry is less important for steam gasification as compared to the oxidation reaction. Further development of the approach must also incorporate the dynamics of surface complexation, which is not considered here.

Thermogravimetric determination of the carbon dioxide reactivity of char from some New Zealand coals and its association with the inorganic geochemistry of the parent coal

Thermogravimetrically-determined carbon dioxide reactivities of chars formed from New Zealand coals, ranging in rank from lignite to high volatile bituminous, vary from 0.12 to 10.63 mg/h/mg on a dry, ash-free basis. The lowest rank subbituminous coal chars have similar reactivities to the lignite coal chars. Calcium content of the char shows the strongest correlation with reactivity, which increases as the calcium content increases. High calcium per se does not directly imply a high char reactivity. Organically-bound calcium catalyses the conversion of carbon to carbon monoxide in the presence of carbon dioxide, whereas calcium present as discrete minerals in the coal matrix, e.g., calcite, fails to significantly affect reactivity. Catalytic effects of magnesium, iron, sodium and phosphorous are not as obvious, but can be recognised for individual chars. The thermogravimetric technique provides a fast, reliable analysis that is able to distinguish char reactivity differences between coals, which may be due to any of the above effects. Published by Elsevier Science B.V.

Reactivity of chars and carbons: New insights through molecular modeling

A new model proposed for the gasification of chars and carbons incorporates features of the turbostratic nanoscale structure that exists in such materials. The model also considers the effect of initial surface chemistry and different reactivities perpendicular to the edges and to the faces of the underlying crystallite planes comprising the turbostratic structure. It may be more realistic than earlier models based on pore or grain structure idealizations when the carbon contains large amounts of crystallite matter. Shrinkage of the carbon particles in the chemically controlled regime is also possible due to the random complete gasification of crystallitic planes. This mechanism can explain observations in the literature of particle size reduction. Based on the model predictions, both initial surface chemistry and the number of stacked planes in the crystallites strongly influence the reactivity and particle shrinkage. Its test results agree well with literature data on the air-oxidation of Spherocarb and show that it accurately predicts the variation of particle size with conversion. Model parameters are determined entirely from rate measurements.

Automated edge-detection technique for measurement of brachial artery reactivity: A comparison of concordance with manual measurements

Concerns have been raised about the reproducibility of brachial artery reactivity (BAR), because subjective decisions regarding the location of interfaces may influence the measurement of very small changes in lumen diameter. We studied 120 consecutive patients with BAR to address if an automated technique could be applied, and if experience influenced reproducibility between two observers, one experienced and one inexperienced. Digital cineloops were measured automatically, using software that measures the leading edge of the endothelium and tracks this in sequential frames and also manually, where a set of three point-to-point measurements were averaged. There was a high correlation between automated and manual techniques for both observers, although less variability was present with expert readers. The limits of agreement overall for interobserver concordance were 0.13 +/-0.65 mm for the manual and 0.03 +/-0.74 mm for the automated measurement. For intraobserver concordance, the limits of agreement were -0.07 +/-0.38 mm for observer 1 and -0.16 +/-0.55 mm for observer 2. We concluded that BAR measurements were highly concordant between observers, although more concordant using the automated method, and that experience does affect concordance. Care must be taken to ensure that the same segments are measured between observers and serially.

Cross-reactivity of Sydney funnel-web spider antivenom: neutralization of the in vitro toxicity of other Australian funnel-web (Atrax and Hadronyche) spider venoms

Australian funnel-web spiders are recognized as one of the most venomous spiders to humans world-wide. Funnel-web spider antivenom (FWS AV) reverses clinical effects of envenomation from the bite of Atrax robustus and a small number of related Hadronyche species. This study assessed the in vitro efficacy of FWS AV in neutralization of the effects of funnel-web spider venoms, collected from various locations along the eastern seaboard of Australia, in an isolated chick biventer cervicis nerve-muscle preparation. Venoms were separated by SDS-PAGE electrophoresis to compare protein composition and transblotted for Western blotting and incubation with FWS AV. SDS-PAGE of venoms revealed similar low and high molecular weight protein bands. Western blotting with FWS AV showed similar antivenom binding with protein bands in all the venoms tested. Male funnel-web spider venoms (7/7) and female venoms (5110) produced muscle contracture and fasciculation when applied to the nerve-muscle preparation. Venom effects were reversed by subsequent application of FWS AV or prevented by pretreatment of the preparation with antivenom. FWS AV appears to reverse the in vitro toxicity of a number of funnel-web spider venoms from the eastern seaboard of Australia. FWS AV should be effective in the treatment of envenomation from most, if not all, species of Australian funnel-web spiders. (C) 2001 Elsevier Science Ltd. All rights reserved.

Structural ordering of coal char during heat treatment and its impact on reactivity

The effect of heat treatment on the structure of an Australian semi-anthracite char was studied in detail in the 850-1150degreesC temperature range using XRD, HRTEM, and electrical resistivity techniques. It was found that the carbon crystallite size in the char does not change significantly during heat treatment in the temperature range studied, for both the raw coal and its ash-free derivative obtained by acid treatment. However, the fraction of the organized carbon in the raw coal chars, determined by XRD, increased with increase of heat treatment time and temperature, while that for the ash-free coal chars remained almost unchanged. This suggests the occurrence of catalytic ordering during heat treatment, supported by the observation that the electrical resistivity of the raw coal chars decreased with heat treatment, while that of the ash-free coal chars did not vary significantly. Further confirmatory evidence was provided by high resolution transmission electron micrographs depicting well-organized carbon layers surrounding iron particles. It is also found that the fraction of organized carbon does not reach unity, but attains an apparent equilibrium value that increases with increase in temperature, providing an apparent heat of ordering of 71.7 kJ mol(-1) in the temperature range studied. Good temperature-independent correlation was found between the electrical resistivity and the organized carbon fraction, indicating that electrical resistivity is indeed structure sensitive. Good correlation was also found between the electrical resistivity and the reactivity of coal char. All these results strongly suggest that the thermal deactivation is the result of a crystallite-perfecting process, which is effectively catalyzed by the inorganic matter in the coal char. Based on kinetic interpretation of the data it is concluded that the process is diffusion controlled, most likely involving transport of iron in the inter-crystallite nanospaces in the temperature range studied. The activation energy of this transport process is found to be very low, at about 11.8 kJ mol(-1), which is corroborated by model-free correlation of the temporal variation of organized carbon fraction as well as electrical resistivity data using the superposition method, and is suggestive of surface transport of iron. (C) 2002 Elsevier Science Ltd. All rights reserved.

Acyl glucuronide reactivity in perspective: biological consequences

The metabolic conjugation of exogenous and endogenous carboxylic acid substrates with endogenous glucuronic acid, mediated by the uridine diphosphoglucuronosyl transferase (UGT) superfamily of enzymes, leads to the formation of acyl glucuronide metabolites. Since the late 1970s, acyl glucuronides have been increasingly identified as reactive electrophilic metabolites, capable of undergoing three reactions: intramolecular rearrangement, hydrolysis, and intermolecular reactions with proteins leading to covalent drug-protein adducts. This essential dogma has been accepted for over a decade. The key question proposed by researchers, and now the pharmaceutical industry, is: does or can the covalent modification of endogenous proteins, mediated by reactive acyl glucuronide metabolites, lead to adverse drug reactions, perhaps idiosyncratic in nature? This review evaluates the evidence for acyl glucuronide-derived perturbation of homeostasis, particularly that which might result from the covalent modification of endogenous proteins and other macromolecules. Because of the availability of acyl glucuronides for test tube/in vitro experiments, there is now a substantial literature documenting their rearrangement, hydrolysis and covalent modification of proteins in vitro. It is certain from in vitro experiments that serum albumin, dipeptidyl peptidase IV, tubulin and UGTs are covalently modified by acyl glucuronides. However, these in vitro experiments have been specifically designed to amplify any interference with a biological process in order to find biological effects. The in vivo situation is not at all clear. Certainly it must be concluded that all humans taking carboxylate drugs that form reactive acyl glucuronides will form covalent drug-protein adducts, and it must also be concluded that this in itself is normally benign. However, there is enough in vivo evidence implicating acyl glucuronides, which, when backed up by in vivo circumstantial and documented in vitro evidence, supports the view that reactive acyl glucuronides may initiate toxicity/immune responses. In summary, though acyl glucuronide-derived covalent modification of endogenous macromolecules is well-defined, the work ahead needs to provide detailed links between such modification and its possible biological consequences. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Electron transfer in acetohydroxy acid synthase as a side reaction of catalysis. implications for the reactivity and partitioning of the carbanion/enamine form of (alpha-hydroxyethyl)thiamin diphosphate in a "nonredox" flavoenzyme

Acetohydroxy acid synthases (AHAS) are thiamin diphosphate- (ThDP-) and FAD-dependent enzymes that catalyze the first common step of branched-chain amino acid biosynthesis in plants, bacteria, and fungi. Although the flavin cofactor is not chemically involved in the physiological reaction of AHAS, it has been shown to be essential for the structural integrity and activity of the enzyme. Here, we report that the enzyme-bound FAD in AHAS is reduced in the course of catalysis in a side reaction. The reduction of the enzyme-bound flavin during turnover of different substrates under aerobic and anaerobic conditions was characterized by stopped-flow kinetics using the intrinsic FAD absorbance. Reduction of enzyme-bound FAD proceeds with a net rate constant of k' = 0.2 s(-1) in the presence of oxygen and approximately 1 s(-1) under anaerobic conditions. No transient flavin radicals are detectable during the reduction process while time-resolved absorbance spectra are recorded. Reconstitution of the binary enzyme-FAD complex with the chemically synthesized intermediate 2-(hydroxyethyl)-ThDP also results in a reduction of the flavin. These data provide evidence for the first time that the key catalytic intermediate 2-(hydroxyethyl)ThDP in the carbanionic/enamine form is not only subject to covalent addition of 2-keto acids and an oxygenase side reaction but also transfers electrons to the adjacent FAD in an intramolecular redox reaction yielding 2-acetyl-ThDP and reduced FAD. The detection of the electron transfer supports the idea of a common ancestor of acetohydroxy acid synthase and pyruvate oxidase, a homologous ThDP- and FAD-dependent enzyme that, in contrast to AHASs, catalyzes a reaction that relies on intercofactor electron transfer.

Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis

Background/aims: Chronic infections such as those caused by Chlamydia pneumoniae and periodontopathic bacteria such as Porphyromonas gingivalis have been associated with atherosclerosis, possibly due to cross-reactivity of the immune response to bacterial GroEL with human heat shock protein (hHSP) 60. Methods: We examined the cross-reactivity of anti-GroEL and anti-P. gingivalis antibodies with hHSP60 in atherosclerosis patients and quantified a panel of six pathogens in atheromas. Results: After absorption of plasma samples with hHSP60, there were variable reductions in the levels of anti-GroEL and anti-P. gingivalis antibodies, suggesting that these antibodies cross-reacted with hHSP60. All of the artery specimens were positive for P. gingivalis. Fusobacterium nucleatum, Tannerella forsythia, C. pneumoniae, Helicobacter pylori, and Haemophilus influenzae were found in 84%, 48%, 28%, 4%, and 4% of arteries, respectively. The prevalence of the three periodontopathic microorganisms, P. gingivalis, F. nucleatum and T. forsythia, was significantly higher than that of the remaining three microorganisms. Conclusions: These results support the hypothesis that in some patients, cross-reactivity of the immune response to bacterial HSPs including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may be a possible mechanism for the association between atherosclerosis and periodontal infection.

Conceptual distinctions among Carver and White's (1994) BAS scales: A reward-reactivity versus trait impulsivity perspective

The 'BIS/BAS scales' (Carver & White, 1994) is the most widely cited inventory for assessing Gray's (1982,1991) Reinforcement Sensitivity Theory (RST) of personality. A peculiarity of this instrument is its three-factor representation of Gray's Behavioural Activation System (BAS), which mediates reactions to reward. While the BAS was initially proposed as the causal basis of Impulsivity, recent arguments suggest that Impulsivity is related to but distinct from reward-reactivity. In this paper, two studies examined Carver and White's BAS scales in terms of factor structure, and convergent/divergent validity when predicting proxies of Impulsivity and reward-reactivity. Confirmatory Factor Analysis revealed structural distinctions between the three BAS scales, and multivariate regression suggested that two of the scales (Drive and Reward-Responsiveness) reflect key concepts of the BAS, while the third (Fun-Seeking) has a broader focus, being equally related to reward-reactivity and Impulsivity. (c) 2005 Elsevier Ltd. All rights reserved.