A generalised dynamic model for char particle gasification with structure evolution and peripheral fragmentation

A generalised model for the prediction of single char particle gasification dynamics, accounting for multi-component mass transfer with chemical reaction, heat transfer, as well as structure evolution and peripheral fragmentation is developed in this paper. Maxwell-Stefan analysis is uniquely applied to both micro and macropores within the framework of the dusty-gas model to account for the bidisperse nature of the char, which differs significantly from the conventional models that are based on a single pore type. The peripheral fragmentation and random-pore correlation incorporated into the model enable prediction of structure/reactivity relationships. The occurrence of chemical reaction within the boundary layer reported by Biggs and Agarwal (Chem. Eng. Sci. 52 (1997) 941) has been confirmed through an analysis of CO/CO2 product ratio obtained from model simulations. However, it is also quantitatively observed that the significance of boundary layer reaction reduces notably with the reduction of oxygen concentration in the flue gas, operational pressure and film thickness. Computations have also shown that in the presence of diffusional gradients peripheral fragmentation occurs in the early stages on the surface, after which conversion quickens significantly due to small particle size. Results of the early commencement of peripheral fragmentation at relatively low overall conversion obtained from a large number of simulations agree well with experimental observations reported by Feng and Bhatia (Energy & Fuels 14 (2000) 297). Comprehensive analysis of simulation results is carried out based on well accepted physical principles to rationalise model prediction. (C) 2001 Elsevier Science Ltd. AH rights reserved.

Peripheral T-Cell tolerance defined through transgenic mouse studies

Selection in the thymus restricted by MHC and self-peptide shapes the diverse reactivities of the T-cell population which subsequently seeds into the peripheral tissues, in anticipation of the universe of pathogen antigens to which the organism may be exposed. A necessary corollary is the potential for T-cell self-reactivity (autoimmunity) in the periphery. Transgenic mouse models in which transgene expression in the thymus is prevented or excluded, have been particularly useful for determining the immunological outcome when T-cells encounter transgene-encoded 'self' antigen in peripheral tissues. Data suggest that non-mutually exclusive mechanisms of T-cells 'ignoring' self-antigen, T-cell deletion, T-cell anergy and T-cell immunoregulation have evolved to prevent self-reactivity while maintaining T-cell diversity. The peripheral T-cell repertoire, far from being static following maturation through the thymus, is in a dynamic stated determined by these peripheral selective and immunoregulatory influences. This article reviews the evidence with particular reference to CD8+ive T-cells.

An investigation of symptom-specific muscle hyperreactivity in upper extremity cumulative trauma disorder

Objective: The study examined symptom-specific muscle hyperreactivity in patients with chronic pain with upper limb cumulative trauma disorder (CTD). Design: Four tasks were presented in counterbalanced order and included neutral, general stressor, personal stressor, and pain stressor tasks. Ratings of stressfulness and recordings of skin conductance level confirmed the effectiveness of the experimental manipulations in inducing stress experiences for all subject groups. Setting: The study was conducted in a university research center. Patients: Thirty patients with CTD were matched as closely as possible for age and gender to control groups of chronic low back pain, arthritis, and pain-Free subjects Outcome Measures: Surface electromyograph recordings were taken from the frontalis, forearm flexors, trapezius, and lower back during baseline and tasks. Results: The study found no evidence of greater muscle tension increases or extended duration of return to baseline for the CTD or low back pain patients at any of the muscle sites for any of the tasks in comparison to control groups. Conclusions: The results indicate that symptom-specific psychophysiological responses may be limited to certain subgroups rather than being characteristic of chronic musculoskeletal pain patients in general.

Detection of dengue viral RNA in Aedes aegypti (Diptera : Culicidae) exposed to sticky lures using reverse-transcriptase polymerase chain reaction

Active surveillance for dengue (DEN) virus infected mosquitoes can be an effective way to predict the risk of dengue infection in a given area. However, doing so may pose logistical problems if mosquitoes must be kept alive or frozen fresh to detect DEN virus. In an attempt to simplify mosquito processing, we evaluated the usefulness of a sticky lure and a seminested reverse-transcriptase polymerase chain reaction assay (RT-PCR) for detecting DEN virus RNA under laboratory conditions using experimentally infected Aedes aegypti (L.) mosquitoes. In the first experiment, 40 male mosquitoes were inoculated with 0.13 mul of a 10(4) pfu/ml DEN-2 stock solution. After a 7-d incubation period, the mosquitoes were applied to the sticky lure and kept at room temperatures of 23-30 degreesC. Following 7,10,14, and 28 d application, 10 mosquitoes each were removed from the lure pooled and assayed for virus. DEN virus nucleic acid was clearly detectable in all pools up to 28 d after death. A second study evaluated sensitivity and specificity using one, two, and five DEN-infected mosquitoes removed after 7, 10, 14, 21 and 30 d application and tested by RT-PCR. All four DEN serotypes were individually inoculated in mosquitoes and evaluated using the same procedures as experiment 1. The four serotypes were detectable in as few as one mosquito 30 d after application to the lure with no evidence of cross-reactivity. The combination of sticky lures and RT-PCR show promise for mosquito and dengue virus surveillance and warrant further evaluation.

Immunoelectron microscopy provides evidence for the presence of mitochondrial heat shock 10-kDa protein (chaperonin 10) in red blood cells and a variety of secretory granules

Hsp10 (10-kDa heat shock protein, also known as chaperonin 10 or Cpn10) is a co-chaperone for Hsp60 in the protein folding process. This protein has also been shown to be identical to the early pregnancy factor, which is an immunosuppressive growth factor found in maternal serum. In this study we have used immunogold electron microscopy to study the subcellular localization of Hsp10 in rat tissues sections embedded in LR Gold resin employing polyclonal antibodies raised against different regions of human Hsp10. In all rat tissues examined including liver, heart, pancreas, kidney, anterior pituitary, salivary gland, thyroid, and adrenal gland, antibodies to Hsp10 showed strong labeling of mitochondria. However, in a number of tissues, in addition to the mitochondrial labeling, strong and highly specific labeling with the Hsp10 antibodies was also observed in several extramitochondrial compartments. These sites included zymogen granules in pancreatic acinar cells, growth hormone granules in anterior pituitary, and secretory granules in PP pancreatic islet cells. Additionally, the mature red blood cells which lack mitochondria, also showed strong reactivity with the Hsp10 antibodies. The observed labeling with the Hsp10 antibodies, both within mitochondria as well as in other compartments/cells, was abolished upon omission of the primary antibodies or upon preadsorption of the primary antibodies with the purified recombinant human Hsp10. These results provide evidence that similar to a number of other recently described mitochondrial proteins (viz., Hsp60, tumor necrosis factor receptor-associated protein- 1, P32 (gC1q-R) protein, and cytochrome c), Hsp10 is also found at a variety of specific extramitochondrial sites in normal rat tissue. These results raise important questions as to how these mitochondrial proteins are translocated to other compartments and their possible function(s) at these sites. The presence of these proteins at extramitochondrial sites in normal tissues has important implications concerning the role of mitochondria in apoptosis and genetic diseases.

Quinolizine-2,4-diones by reversible dimerisation 2-pyridylketenes

Quinolizine-2,4-diones 11 are obtained by ash vacuum thermolysis (FVT) of 3-acyl-1,2,3-triazolo[1,5-a]pyridines 7. The reaction takes place via methyl- and phenyl(2-pyridyl)ketenes 10, which are directly observable by infrared spectroscopy in low temperature matrices. FVT of 11 regenerates the ketenes 10.

The radiation chemistry of ultem at 77 K as revealed by ESR spectroscopy

Radical formation in ultem following gamma-radiolysis has been reassessed, and the G(R*) values at different temperatures have been determined by ESR spectroscopy. The radical assignment and radical reactivity have been re-examined by photobleaching and thermal annealing studies. Photobleachable radical anions were found to comprise approximate to40% of the total number of radicals formed on radiolysis at 77 K. Spectral subtraction methods, ESR spectral simulations, measurement of g-values and the hyperfine splitting constants were used to identify the other radical intermediates. The principal chain scission radicals are formed due to scission of the main-chain at (i) the ether linkage, (ii) the isopropylidene group and (iii) the imide ring in the main chain. The side chain methyl groups of the isopropylidine units also lose hydrogen to form methylene radicals. The five-line spectrum observed to decay in the temperature range 370-430 K, which has not been assigned previously, has been identified as being characteristic of a di-substituted benzyl radical. (C) 2002 Elsevier Science Ltd. All rights reserved.

The copolymerization of N-vinyl-2-pyrrolidone with 2-hydroxyethyl methacrylate

The bulk free radical copolymerization of 2-hydroxyethyl methacrylate (HEMA) with N-vinyl-2-pyrrolidone (VP) was carried out to low conversions at 50 degreesC, using benzoyl peroxide (BPO) as initiator. The compositions of the copolymers; were determined using C-13 NMR spectroscopy. The conversion of monomers to polymers was studied using FT-NIR spectroscopy in order to predict the extent of conversion of monomer to polymer. From model fits to the composition data, a statistical F-test revealed that die penultimate model describes die copolymerization better than die terminal model. Reactivity ratios were calculated by using a non-linear least squares analysis (NLLS) and r(H) = 8.18 and r(V) = 0.097 were found to be the best fit values of the reactivity ratios for the terminal model and r(HH) = 12.0, r(VH) = 2.20, r(VV) = 0.12 and r(HV) = 0.03 for the penultimate model. Predictions were made for changes in compositions as a function of conversion based upon the terminal and penultimate models.

From molecular complexes to zwitterions and final products. Reactions between C3O2 and amines

The formation of molecular complexes (prereactive intermediates) between C3O2 and amines (ammonia, dimethylamine, trimethylamine, and 4-(dimethylamino)pyridine) as well as the subsequent transformation of the complexes into C3O2-amine zwitterions in cryogenic matrixes (ca. 40 K) has been observed. In the case of dimethylamine, the formation of tetramethylmalonamide has also been documented. Calculations using density functional theory (B3LYP/6-31G(2d, p)) are used to assign all above species and are in excellent agreement with the IR spectra.

Inhibition of tubulin assembly and covalent binding to microtubular protein by valproic acid glucuronide in vitro

Acyl glucuronides are reactive metabolites of carboxylate drugs, able to undergo a number of reactions in vitro and in vivo, including isomerization via intramolecular rearrangement and covalent adduct formation with proteins. The intrinsic reactivity of a particular acyl glucuronide depends upon the chemical makeup of the drug moiety. The least reactive acyl glucuronide yet reported is valproic acid acyl glucuronide (VPA-G), which is the major metabolite of the antiepileptic agent valproic acid (VPA). In this study, we showed that both VPA-G and its rearrangement isomers (iso-VPA-G) interacted with bovine brain microtubular protein (MTP, comprised of 85% tubulin and 15% microtubule associated proteins {MAPs}). MTP was incubated with VPA, VPA-G and iso-VPA-G for 2 h at room temperature and pH 7.5 at various concentrations up to 4 mM. VPA-G and iso-VPA-G caused dose-dependent inhibition of assembly of MTP into microtubules, with 50% inhibition (IC50) values of 1.0 and 0.2 mM respectively, suggesting that iso-VPA-G has five times more inhibitory potential than VPA-G. VPA itself did not inhibit microtubule formation except at very high concentrations (greater than or equal to2 mM). Dialysis to remove unbound VPA-G and iso-VPA-G (prior to the assembly assay) diminished inhibition while not removing it. Comparison of covalent binding of VPA-G and iso-VPA-G (using [C-14]-labelled species) showed that adduct formation was much greater for iso-vTA-G. When [C-14]-iso-VPA-G was reacted with MTP in the presence of sodium cyanide (to stabilize glycation adducts), subsequent separation into tubulin and MAPs fractions by ion exchange chromatography revealed that 78 and 22% of the covalent binding occurred with the MAPs and tubulin fractions respectively. These experiments support the notion of both covalent and reversible binding playing parts in the inhibition of microtubule formation from MTP (though the acyl glucuronide of VPA is less important than its rearrangement isomers in this regard), and that both tubulin and (perhaps more importantly) MAPs form adducts with acyl glucuronides. (C) 2002 Elsevier Science Inc. All rights reserved.

A cassette ligation strategy with thioether replacement of three Gly-Gly peptide bonds: Total chemical synthesis of the 101 residue protein early pregnancy factor [psi(CH2S)(28-29,56-57,76-77)]

The 101 residue protein early pregnancy factor (EPF), also known as human chaperonin 10, was synthesized from four functionalized, but unprotected, peptide segments by a sequential thioether ligation strategy. The approach exploits the differential reactivity of a peptide-NHCH2CH2SH thiolate with XCH2CO-peptides, where X = Cl or I/Br. Initial model studies with short functionalized (but unprotected) peptides showed a significantly faster reaction of a peptide-NHCH2CH2SH thiolate with a BrCH2CO-peptide than with a CICH2CO-peptide, where thiolate displacement of the halide leads to chemoselective formation of a thioether surrogate for the Gly-Gly peptide bond. This rate difference was used as the basis of a novel sequential ligation approach to the synthesis of large polypeptide chains. Thus, ligation of a model bifunctional N-alpha-chloroacetyl, C-terminal thiolated peptide with a second N-alpha-bromoacetyl peptide demonstrated chemoselective bromide displacement by the thiol group. Further investigations showed that the relatively unreactive N-alpha-chloroacetyl peptides could be activated by halide exchange using saturated KI solutions to yield the highly reactive No-iodoacetyl peptides. These findings were used to formulate a sequential thioether ligation strategy for the synthesis of EPF, a 101 amino acid protein containing three Gly-Gly sites approximately equidistantly spaced within the peptide chain. Four peptide segments or cassettes comprising the EPF protein sequence (BrAc-[EPF 78-101] 12, ClAc-[EPF 58-75]-[NHCH2CH2SH] 13, ClAc-[EPF 30-55]-[NHCH2CH2SH] 14, and Ac-[EPF 1-27]-[NHCH2CH2SH] 15) of EPF were synthesized in high yield and purity using Boc SPPS chemistry. In the stepwise sequential ligation strategy, reaction of peptides 12 and 13 was followed by conversion of the N-terminal chloroacetyl functional group to an iodoacetyl, thus activating the product peptide for further ligation with peptide 14. The process of ligation followed by iodoacetyl activation was repeated to yield an analogue of EPF (EPF psi(CH2S)(28-29,56-57,76-77)) 19 in 19% overall yield.

Kinetic parameters associated with self-heating of New Zealand coals under adiabatic conditions

Adiabatic self-heating tests were carried out on five New Zealand coal samples ranging in rank from lignite to high-volatile bituminous. Kinetic parameters of oxidation were obtained front the self-heating curves assuming Arrhenius behaviour. The activation energy E (kJ mol(-1)) and the pre-exponential factor A (s(-1)) were determined in the temperature range of 70-140 degreesC. The activation energy exhibited a definite rank relationship with a minimum E of 55 kJ mol(-1) occurring at a Suggate rank of similar to6.2 corresponding to subbituminous C. Either side of this rank there was a noticeable increase in the activation energy indicating lower reactivity of the coal. A similar rank trend was also observed in the R-70 self-heating rate index values that were taken from the initial portion of the self-heating curve front 40 to 70 degreesC. From these results it is clear that the adiabatic method is capable of providing reliable kinetic parameters of coal oxidation.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Human melanoblasts in culture: Expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3

The BRN2 transcription factor (POU3F2, N-Oct-3) has been implicated in development of the melanocytic lineage and in melanoma. Using a low calcium medium supplemented with stem cell factor, fibroblast growth factor-2, endothelin-3 and cholera toxin, we have established and partially characterised human melanocyte precursor cells, which are unpigmented, contain immature melanosomes and lack L-dihydroxyphenylalanine reactivity. Melanoblast cultures expressed high levels of BRN2 compared to melanocytes, which decreased to a level similar to that of melanocytes when cultured in medium that contained phorbol ester but lacked endothelin-3, stem cell factor and fibroblast growth factor-2. This decrease in BRN2 accompanied a positive L-dihydroxyphenylalanine reaction and induction of melanosome maturation consistent with melanoblast differentiation seen during development. Culture of primary melanocytes in low calcium medium supplemented with stem cell factor, fibroblast growth factor-2 and endothelin-3 caused an increase in BRN2 protein levels with a concomitant change to a melanoblast-like morphology. Synergism between any two of these growth factors was required for BRN2 protein induction, whereas all three factors were required to alter melanocyte morphology and for maximal BRN2 protein expression. These finding implicate BRN2 as an early marker of melanoblasts that may contribute to the hierarchy of melanocytic gene control.