A continuum receptor model of hepatic lipoprotein metabolism

A mathematical model describing the uptake of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles by a single hepatocyte cell is formulated and solved. The model includes a description of the dynamic change in receptor density on the surface of the cell due to the binding and dissociation of the lipoprotein particles, the subsequent internalisation of bound particles, receptors and unbound receptors, the recycling of receptors to the cell surface, cholesterol dependent de novo receptor formation by the cell and the effect that particle uptake has on the cell's overall cholesterol content. The effect that blocking access to LDL receptors by VLDL, or internalisation of VLDL particles containing different amounts of apolipoprotein E (we will refer to these particles as VLDL-2 and VLDL-3) has on LDL uptake is explored. By comparison with experimental data we find that measures of cell cholesterol content are important in differentiating between the mechanisms by which VLDL is thought to inhibit LDL uptake. We extend our work to show that in the presence of both types of VLDL particle (VLDL-2 and VLDL-3), measuring relative LDL uptake does not allow differentiation between the results of blocking and internalisation of each VLDL particle to be made. Instead by considering the intracellular cholesterol content it is found that internalisation of VLDL-2 and VLDL-3 leads to the highest intracellular cholesterol concentration. A sensitivity analysis of the model reveals that binding, unbinding and internalisation rates, the fraction of receptors recycled and the rate at which the cholesterol dependent free receptors are created by the cell have important implications for the overall uptake dynamics of either VLDL or LDL particles and subsequent intracellular cholesterol concentration. (C) 2008 Elsevier Ltd. All rights reserved.

Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell

Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area.

Dynamics of QoI sensitivity in Mycosphaerella fijiensis in Costa Rica during 2000 to 2003

From 1997 onward, the strobilurin fungicide azoxystrobin was widely used in the main banana-production zone in Costa Rica against Mycosphaerella fijiensis var. difformis causing black Sigatoka of banana. By 2000, isolates of M. fijiensis with resistance to the quinolene oxidase inhibitor fungicides were common on some farms in the area. The cause was a single point mutation from glycine to alanine in the fungal target protein, cytochrome b gene. An amplification refractory mutation system Scorpion quantitative polymerase chain reaction assay was developed and used to determine the frequency of G 143A allele in samples of M. fijiensis. Two hierarchical surveys of spatial variability, in 2001 and 2002,found no significant variation in frequency on spatial scales <10 in. This allowed the frequency of G143A alleles on a farm to be estimated efficiently by averaging single samples taken at two fixed locations. The frequency of G 143A allele in bulk samples from I I farms throughout Costa Rica was determined at 2-month intervals. There was no direct relationship between the number of spray applications and the frequency of G143A on individual farms. Instead, the frequency converged toward regional averages, presumably due to the large-scale mixing of ascospores dispersed by wind. Using trap plants in an area remote from the main producing area, immigration of resistant ascospores was detected as far as 6 km away both with and against the prevailing wind.

Inhibition of coxsackie B virus infection by soluble forms of its receptors: Binding affinities, altered particle formation, and competition with cellular receptors

We previously reported that soluble decay-accelerating factor (DAF) and coxsackievirus-adenovirus receptor (CAR) blocked coxsackievirus 133 (CVB3) myocarditis in mice, but only soluble CAR blocked CVB3-mediated pancreatitis. Here, we report that the in vitro mechanisms of viral inhibition by these soluble receptors also differ. Soluble DAF inhibited virus infection through the formation of reversible complexes with CVB3, while binding of soluble CAR to CVB induced the formation of altered (A) particles with a resultant irreversible loss of infectivity. A-particle formation was characterized by loss of VP4 from the virions and required incubation of CVB3-CAR complexes at 37 degrees C. Dimeric soluble DAF (DAF-Fc) was found to be 125-fold-more effective at inhibiting CVB3 than monomeric DAF, which corresponded to a 100-fold increase in binding affinity as determined by surface plasmon resonance analysis. Soluble CAR and soluble dimeric CAR (CAR-Fc) bound to CVB3 with 5,000- and 10,000-fold-higher affinities than the equivalent forms of DAF. While DAF-Fc was 125-fold-more effective at inhibiting virus than monomeric DAF, complement regulation by DAF-Fc was decreased 4 fold. Therefore, while the virus binding was a cooperative event, complement regulation was hindered by the molecular orientation of DAF-Fc, indicating that the regions responsible for complement regulation and virus binding do not completely overlap. Relative contributions of CVB binding affinity, receptor binding footprint on the virus capsid, and induction of capsid conformation alterations for the ability of cellular DAF and CAR to act as receptors are discussed.

13C-2H correlation NMR spectroscopy studies of the in vivo transformations of natural products from Artemisia annua

13C-2H correlation NMR spectroscopy (13C-2H COSY) permits the identification of 13C and 2H nuclei which are connected to one another by a single chemical bond via the sizeable 1JCD coupling constant. The practical development of this technique is described using a 13C-2H COSY pulse sequence which is derived from the classical 13C-1H correlation experiment. An example is given of the application of 13C-2H COSY to the study of the biogenesis of natural products from the anti-malarial plant Artemisia annua, using a doubly-labelled precursor molecule. Although the biogenesis of artemisinin, the anti-malarial principle from this species, has been extensively studied over the past twenty years there is still no consensus as to the true biosynthetic route to this important natural product – indeed, some published experimental results are directly contradictory. One possible reason for this confusion may be the ease with which some of the metabolites from A. annua undergo spontaneous autoxidation, as exemplified by our recent in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid, and the application of 13C-2H COSY to this biosynthetic problem has been important in helping to mitigate against such processes. In this in vivo application of 13C-2H COSY, [15-13C2H3]-dihydroartemisinic acid (the doubly-labelled analogue of the natural product from this species which was obtained through synthesis) was fed to A. annua plants and was shown to be converted into several natural products which have been described previously, including artemisinin. It is proposed that all of these transformations occurred via a tertiary hydroperoxide intermediate, which is derived from dihyroartemisinic acid. This intermediate was observed directly in this feeding experiment by the 13C-2H COSY technique; its observation by more traditional procedures (e.g., chromatographic separation, followed by spectroscopic analysis of the purified product) would have been difficult owing to the instability of the hydroperoxide group (as had been established previously by our in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid). This same hydroperoxide has been reported as the initial product of the spontaneous autoxidation of dihydroartemisinic acid in our previous in vitro studies. Its observation in this feeding experiment by the 13C-2H COSY technique, a procedure which requires the minimum of sample manipulation in order to achieve a reliable identification of metabolites (based on both 13C and 2H chemical shifts at the 15-position), provides the best possible evidence for its status as a genuine biosynthetic intermediate, rather than merely as an artifact of the experimental procedure.

Carbon-decorated FePt nanoparticles

FePt magnetic nanoparticles are an important candidate material for many future magnetic applications. FePt exists as two main phases, that is, a disordered face-centered cubic (fcc) structure, which is generally prepared by chemical methods at low temperatures, and the high-temperature chemically ordered face-centered tetragonal (fct) structure. The fee FePt, with low coercivity but associated with superparamagnetic properties, may find applications as a magnetic fluid or as a nanoscale carrier for chemical or biochemical species in biomedical areas, while fct FePt is proposed for use in ultrahigh-density magnetic recording applications. However, for both of these applications an enhancement of the intrinsically weak magnetic properties, the avoidance of magnetic interferences from neighbor particles, and the improved stability of the small magnetic body remain key practical issues. We report a simple synthetic method for producing FePt nanoparticles that involves hydrothermal treatment of Fe and Pt precursors in glucose followed by calcination at 900 degrees C. This new method produces thermally stable spheroidal graphite nanoparticles (large and fullerene-like) that encapsulate or decorate FePt particles of ca. 5 nm with no severe macroscopic particle coalescence. Also, a low coercivity of the material is recorded; indicative of small magnetic interference from neighboring carbon-coated particles. Thus, this simple synthetic method involves the use of a more environmentally acceptable glucose/aqueous phase to offer a protective coating for FePt nanoparticles. It is also believed that such a synthetic protocol can be readily extended to the preparation of other graphite-coated magnetic iron alloys of controlled size, stoichiometry, and physical properties.

Chemical, physical and electrical properties of aged dodecylbenzene 2: thermal ageing of single isomers in air

The linear isomer of dodecylbenzene (DDB), 1-phenyldodecane, was aged at temperatures of 105 and 135 degrees C in air and the resultant products were analyzed using a range of analytical techniques. On ageing, the 1-phenyldodecane darkened, the acid number, dielectric loss and water content increased and significant oxidation peaks were detected in the infrared spectrum. When aged in the presence of copper, a characteristic peak at 680 nm was also detected by UV/visible spectroscopy but, compared with previous studies of a cable-grade DDB, the strength of this peak was much increased and no appreciable precipitate formation occurred. At the same time, very high values of dielectric loss were recorded. On ageing in the absence of copper, an unusually strong infrared carbonyl band was seen, which correlates well with the detection of dodecanophenone by gas chromatography / mass spectrometry and nuclear magnetic resonance spectroscopy. It was therefore concluded that the ageing process proceeds via the initial production of aromatic ketones, which may then be further oxidized to carboxylic acids. In the presence of copper, these oxidation products are present in lower quantities, most of these oxidation products being combined with the copper present in the oil to give copper carboxylates. The behavior is described in terms of a complex autoxidation mechanism, in which copper acts as both an oxidizing and a reducing agent, depending on its oxidation state and, in particular, promotes elimination via the oxidation of intermediate alkyl radical species to carbocations.

Low-temperature sol-gel preparation of ordered nanoparticles of tungsten carbide/oxide

Tungsten carbide/oxide particles have been prepared by the gel precipitation of tungstic acid in the presence of an organic gelling agent [10% ammonium poly(acrylic acid) in water, supplied by Ciba Specialty Chemicals]. The feed solution; a homogeneous mixture of sodium tungstate and ammonium poly(acrylic acid) in water, was dropped from a 1-mm jet into hydrochloric acid saturated hexanol/concentrated hydrochloric acid to give particles of a mixture of tungstic acid and poly(acrylic acid), which, after drying in air at 100 degrees C and heating to 900 degrees C in argon for 2 h, followed by heating in carbon dioxide for a further 2 h and cooling, gives a mixture of WO, WC, and a trace of NaxWO3, with the carbon for the formation of WC being provided by the thermal carbonization of poly(acrylic acid). The pyrolyzed product is friable and easily broken down in a pestle and mortar to a fine powder or by ultrasonics, in water, to form a stable colloid. The temperature of carbide formation by this process is significantly lower (900 degrees C) than that reported for the commercial preparation of tungsten carbide, typically > 1400 degrees C. In addition, the need for prolonged grinding of the constituents is obviated because the reacting moieties are already in intimate contact on a molecular basis. X-ray diffraction, particle sizing, transmission electron microscopy, surface area, and pore size distribution studies have been carried out, and possible uses are suggested. A flow diagram for the process is described.

Gas-solid reactions of single crystals: a study of reactions of NH3 and NO2 with single crystalline organic substrates by infrared microspectroscopy

Reaction of single crystals of benzoic and trans-cinnamic acids with 200 Torr pressure of ammonia gas in a sealed glass bulb at 20 degrees C generates the corresponding ammonium salts; there is no sign of any 1:2 adduct as has been reported previously for related systems. Isotopic substitution using ND3 has been used to aid identification of the products. Adipic acid likewise reacts with NH3 gas to form a product in which ammonium salts are formed at both carboxylic acid groups. Reaction of 0.5 Torr pressure of NO2 gas with single crystals of 9-methylanthracene and 9-anthracenemethanol in a flow system generates nitrated products where the nitro group appears to be attached at the 10-position, i.e. the position trans to the methyl or methoxy substituent on the central ring. Isotopic substitution using (NO2)-N-15 has been used to confirm the identity of the bands arising from the coordinated NO2 group. The products formed when single crystals of hydantoin are reacted with NO2 gas under similar conditions depend on the temperature of the reaction. At 20 degrees C, a nitrated product is formed, but at 65 degrees C this gives way to a product containing no nitro groups. The findings show the general applicability of infrared microspectroscopy to a study of gas-solid reactions of organic single crystals. (c) 2005 Elsevier B.V. All rights reserved.

Analysis of ochres from Clearwell Caves: the role of particle size in determining colour

Three ochre samples (A (orange-red in colour), B (red) and C (purple)) from Clearwell Caves, (Gloucestershire, UK) have been examined using an integrated analytical methodology based on the techniques of IR and diffuse reflectance UV-visible-NIR spectroscopy, X-ray diffraction, elemental analysis by ICP-AES and particle size analysis. It is shown that the chromophore in each case is haematite. The differences in colour may be accounted for by (i) different mineralogical and chemical composition in the case of the orange ochre, where hi,,her levels of dolomite and copper are seen and (ii) an unusual particle size distribution in the case of the purple ochre. When the purple ochre was ground to give the same particle size distribution as the red ochre then the colours of the two samples became indistinguishable. An analysis has now been completed of a range of ochre samples with colours from yellow to purple from the important site of Clearwell Caves. (C) 2004 Elsevier B.V. All rights reserved.

Micelle-hosted palladium nanoparticles catalyze citral molecule hydrogenation in supercritical carbon dioxide

A new approach of employing metal particles in micelles for the hydrogenation of organic molecules in the presence of fluorinated surfactant and water in supercritical carbon dioxide has very recently been introduced. This is allegedly to deliver many advantages for carrying out catalysis including the use of supercritical carbon dioxide (scCO(2)) as a greener solvent. Following this preliminary account, the present work aims to provide direct visual evidence on the formation of metal microemulsions and to investigate whether metal located in the soft micellar assemblies could affect reaction selectivity. Synthesis of Pd nanoparticles in perfluorohydrocarboxylate anionic micelles in scCO(2) is therefore carried out in a stainless steel batch reactor at 40 degreesC and in a 150 bar CO2/H-2 mixture. Homogeneous dispersion of the microemulsion containing Pd nanoparticles in scCO(2) is observed through a sapphire window reactor at W-0 ratios (molar water-to-surfactant ratios) ranging from 2 to 30. It is also evidenced that the use of micelle assemblies as new metal catalyst nanocarriers could indeed exert a great influence on product selectivity. The hydrogenation of a citral molecule that contains three reducible groups (aldehyde, double bonds at the 2,3-position and the 6,7-position) is studied. An unusually high selectivity toward citronellal (a high regioselectivity toward the reduction of the 2,3-unsaturation) is observed in supercritical carbon dioxide. On the other hand, when the catalysis is carried out in the conventional liquid or vapor phase over the same reaction time, total hydrogenation of the two double bonds is achieved. It is thought that the high kinetic reluctance for double bond hydrogenation of the citral molecule at the hydrophobic end (the 6,7-position) is due to the unique micelle environment that is in close proximity to the metal surface in supercritical carbon dioxide that guides a head-on attack of the molecule toward the core metal particle.

Analysis of red and yellow ochre samples from Clearwell Caves and Catalhoyuk by vibrational spectroscopy and other techniques

Ochre samples excavated from the neolithic site at Qatalhoyuk, Turkey have been compared with "native" ochres from Clearwell Caves, UK using infrared spectroscopy backed up by Raman spectroscopy, scanning electron microscopy (with energy-dispersive X-rays (EDX) analysis), powder X-ray diffraction, diffuse reflection UV-Vis and atomic absorption spectroscopies. For the Clearwell Caves ochres, which range in colour from yellow-orange to red-brown, it is shown that the colour is related to the nature of the chromophore present and not to any differences in particle size. The darker red ochres contain predominantly haematite while the yellow ochre contains only goethite. The ochres from Qatalhoyuk contain only about one-twentieth of the levels of iron found in the Clearwell Caves ochres. The iron oxide pigment (haematite in all cases studied here) has been mixed with a soft lime plaster which also contains calcite and silicate (clay) minerals. (C) 2003 Elsevier B.V. All rights reserved.

Novel lanthanide luminescent materials based on complexes of 3-hydroxypicolinic acid and silica nanoparticles

New lanthanide complexes of 3-hydroxypicolinic acid (HpicOH) were prepared: [Ln(H2O)(picOH)(2)(mu-HpicO)].3H(2)O (Ln = Eu, Tb, Er). The complexes were characterized using photoluminescence, infrared, Raman, and H-1 NMR spectroscopy, and elemental analysis. The crystal structure of [Eu(H2O)(picOH)(2)(mu-HpicO)] . 3H(2)O 1 was determined by X-ray diffraction. Compound 1 crystallizes in a monoclinic system with space group P2(1)/c and cell parameters a = 9.105(13) Angstrom, b = 18.796(25) Angstrom, and c = 13.531(17) Angstrom, and beta = 104.86(1) deg. The 3-hydroxypicolinate ligands coordinate through both N,O- or O,O- chelation to the lanthanide ions, as shown by X-ray and spectroscopic results. Photoluminescence measurements were performed for the Eu(III) and Tb(III) complexes; the Eu(III) complex was investigated in more detail. The Eu(III) compound is highly luminescent and acts as a photoactive center in nanocomposite materials whose host matrixes are silica nanoparticles.

Engineering of a monodisperse core-shell magnetic Ti-O-Si oxidation nanocatalyst

There has been limited development in catalyst carriers for magnetic separations where superparamagnetic nanoparticles of a high saturation magnetization with no coercivity are required to isolate expensive catalyst reagent that are subjected to repeated magnetic cycles. By using simple stepwise layer-by-layer nanochemistry techniques, we show that an fee FePt nanomagnet can be created inside each silica particle with tailored dimensions to great precision. Subsequent engineering of the external surface with Ti-O-Si species in an optimum structure to create a unique interface gives high activity and excellent selectivity of the composite material for the trans-stilbene oxidation to the corresponding epoxide in the presence of tert-butyl hydroperoxide. Thus, a new magnetic separable epoxidation catalyst is described. This work clearly demonstrates the significance of nanoengineering of a single catalyst particle by a bottom-up construction approach in modern catalyst design, which could lead to new catalytic. properties.

Silica-encapsulated nanomagnetic particle as a new recoverable biocatalyst carrier

Enzymes are versatile biocatalysts with major advantages of ultrahigh reaction selectivity and specificity under mild conditions, which currently find increasing applications. However, their applications are often hampered by difficulties in recovery and recycling. As a result, we carried out detailed investigations on the synthesis and characterization of silica-encapsulated iron oxide magnetic nanoparticles of controlled dimension as an enzyme carrier. It is shown that the relatively smaller sized silica-coated magnetic nanoparticle prepared by the microemlusion technique can a carry bulky enzyme, beta-lactamase, via chemical linkages on the silica overlayer without severely blocking the enzymatic active center ( which is commonly encountered in conventional solid supports). An activity study by Michalis-Menten kinetics reflects that this new type of immobilization allows enzyme isolation with accessibility as good as free enzyme. The recovery and reusability of the nanoparticle-supported enzyme upon application of magnetic separation are also demonstrated.