163 resultados para Posttranslational modification
Resumo:
In this article, a new hybrid model for estimating the pore size distribution of micro- and mesoporous materials is developed, and tested with the adsorption data of nitrogen, oxygen, and argon on ordered mesoporous materials reported in the literature. For the micropore region, the model uses the Dubinin-Rudushkevich (DR) isotherm with the Chen-Yang modification. A recent isotherm model of the authors for nonporous materials, which uses a continuum-mechanical model for the multilayer region and the Unilan model for the submonolayer region, has been extended for adsorption in mesopores. The experimental data is inverted using regularization to obtain the pore size distribution. The present model was found to be successful in predicting the pore size distribution of pure as well as binary physical mixtures of MCM-41 synthesized with different templates, with results in agreement with those from the XRD method and nonlocal density functional theory. It was found that various other recent methods, as well as the classical Broekhoff and de Beer method, underpredict the pore diameter of MCM-41. The present model has been successfully applied to MCM-48, SBA's, CMK, KIT, HMS, FSM, MTS, mesoporous fly ash, and a large number of other regular mesoporous materials.
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In two experiments we investigated the effect of generalized orienting induced by changing the modality of the lead stimulus on the modulation of blink reflexes elicited by acoustic stimuli. In Experiment 1 (n = 32), participants were presented with acoustic or visual change stimuli after habituation training with tactile lead stimuli. In Experiment 2 (n = 64), modality of the lead stimulus (acoustic vs. visual) was crossed with experimental condition (change vs. no change). Lead stimulus change resulted in increased electrodermal orienting in both experiments. Blink latency shortening and blink magnitude facilitation increased from habituation to change trials regardless of whether the change stimulus was presented in the same or in a different modality as the reflex-eliciting stimulus. These results are not consistent with modality-specific accounts of attentional startle modulation.
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Mesoporous Mobil catalytic materials of number 41 (MCM-41) silica was chemically modified using both inorganic and organic precursors and characterized using the techniques, XRD, XPS, MAS NMR, FTIR, W-Vis, and physical adsorption of nitrogen, hydrocarbons (hexane, benzene, acetone, and methanol) and water vapor. Modification using organic reagents was found to result in a significant loss in porosity and a shape change of surface properties (increased hydrophobicity and decreased acidity). With inorganic modifying reagents, the decrease in porosity was also observed while the surface properties were not significantly altered as reflected by the adsorption isotherms of organics and water vapors. Chemical modifications can greatly improve the hydrothermal stability of MCM-41 material because of the enhanced surface hydrophobicity (with organic modifiers) or increased pore wall thickness (with inorganic modifiers). (C) 2000 Elsevier Science B.V. All rights reserved.
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A major challenge associated with using large chemical libraries synthesized on microscopic solid support beads is the rapid discrimination of individual compounds in these libraries. This challenge can be overcome by encoding the beads with 1 mum silica colloidal particles (reporters) that contain specific and identifiable combinations of fluorescent byes. The colored bar code generated on support beads during combinatorial library synthesis can be easily, rapidly, and inexpensively decoded through the use of fluorescence microscopy. All reporters are precoated with polyelectrolytes [poly(acrylic acid), PAA, poly(sodium 4-styrenesulfonate PSSS, polyethylenimine, PEI, and/or poly(diallyldimethylammonium chloride), PDADMAC] with the aim of enhancing surface charge, promoting electrostatic attraction to the bead, and facilitating polymer bridging between the bead and reporter for permanent adhesion. As shown in this article, reporters coated with polyelectrolytes clearly outperform uncoated reporters with regard to quantity of attached reporters per bead (54 +/- 23 in 2500 mum(2) area for PEI/PAA coated and 11 +/- 6 for uncoated reporters) and minimization of cross-contamination (1 red reporter in 2500 mum(2) area of green-labeled bead for PEI/PAA coated and 26 +/- 15 red reporters on green-labeled beads for uncoated reporters after 10 days). Examination of various polyelectrolyte systems shows that the magnitude of the xi -potential of polyelectrolyte-coated reporters (-64 mV for PDADMAC/PSSS and -42 mV for PEI/PAA-coated reporters) has no correlation with the number of reporters that adhere to the solid support beads (21 +/- 16 in 2500 mum(2) area for PDADMAC/PSSS and 54 +/- 23 for PEI/PAA-coated reporters). The contribution of polymer bridging to the adhesion has a far greater influence than electrostatic attraction and is demonstrated by modification of the polyelectrolyte multilayers using gamma irradiation of precoated reporters either in aqueous solution or in polyelectrolyte solution.
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Human N-acetyltransferase 1 (NAT1) is a widely distributed enzyme that catalyses the acetylation of arylamine and hydrazine drugs as well as several known carcinogens, and so its levels in the body may have toxicological importance with regard to drug toxicity and cancer risk. Recently, we showed that p-aminobenzoic acid (PABA) was able to down-regulate human NAT1 in cultured cells, but the exact mechanism by which PABA acts remains unclear. In the present study, we investigated the possibility that PABA-induced down-regulation involves its metabolism to N-OH-PABA, since N-OH-AAF functions as an irreversible inhibitor of hamster and rat NAT1. We show here that N-OH-PABA irreversibly inactivates human NAT1 both in cultured cells and cell cytosols in a time- and concentration-dependent manner. Maximal inactivation in cultured cells occurred within 4 hr of treatment, with a concentration of 30 muM reducing activity by 60 +/- 7%. Dialysis studies showed that inactivation was irreversible, and cofactor (acetyl coenzyme A) but not substrate (PABA) completely protected against inactivation, indicating involvement of the cofactor-binding site. In agreement with these data, kinetic studies revealed a 4-fold increase in cofactor K-m, but no change in substrate K-m for N-OH-PABA-treated cytosols compared to control. We conclude that N-OH-PABA decreases NAT1 activity by a direct interaction with the enzyme and appears to be a result of covalent modification at the cofactor-binding site. This is in contrast to our findings for PABA, which appears to reduce NAT1 activity by down-regulating the enzyme, leading to a decrease in NAT1 protein content. BIOCHEM PHARMACOL 60;12: 1829-1836, 2000. (C) 2000 Elsevier Science Inc.
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Growth factors and their binding proteins are important proteins regulating mammalian cell proliferation and differentiation so there is considerable interest in producing them as recombinant proteins, especially in hosts that do not already produce a complex mixture of growth factors. Many growth factors require posttranslational modifications making them unsuitable for production in Escherichia coli or other prokaryotes. Since several expression vector systems have been recently developed for foreign protein production in the cellular slime mould, Dictyostelium discoideum, we attempted to use two of these systems to express human insulin-like growth factor binding protein 6 (hIGFBP6) and bovine beta-cellulin (bBTC) as secreted proteins. Although both proteins were successfully produced in stably transformed amoebae, no secretion was detected in spite of several attempts to facilitate this occurring.
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This paper presents a means of structuring specifications in real-time Object-Z: an integration of Object-Z with the timed refinement calculus. Incremental modification of classes using inheritance and composition of classes to form multi-component systems are examined. Two approaches to the latter are considered: using Object-Z's notion of object instantiation and introducing a parallel composition operator similar to those found in process algebras. The parallel composition operator approach is both more concise and allows more general modelling of concurrency. Its incorporation into the existing semantics of real-time Object-Z is presented.
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Visual pigments, the molecules in photoreceptors that initiate the process of vision, are inherently dichroic, differentially absorbing light according to its axis of polarization. Many animals have taken advantage of this property to build receptor systems capable of analyzing the polarization of incoming light, as polarized light is abundant in natural scenes (commonly being produced by scattering or reflection). Such polarization sensitivity has long been associated with behavioral tasks like orientation or navigation. However, only recently have we become aware that it can be incorporated into a high-level visual perception akin to color vision, permitting segmentation of a viewed scene into regions that differ in their polarization. By analogy to color vision, we call this capacity polarization vision. It is apparently used for tasks like those that color vision specializes in: contrast enhancement, camouflage breaking, object recognition, and signal detection and discrimination. While color is very useful in terrestrial or shallow-water environments, it is an unreliable cue deeper in water due to the spectral modification of light as it travels through water of various depths or of varying optical quality. Here, polarization vision has special utility and consequently has evolved in numerous marine species, as well as at least one terrestrial animal. In this review, we consider recent findings concerning polarization vision and its significance in biological signaling.
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The major limiting factor in the successful application of adjuvant therapy for metastatic disease is the lack of adjuvant specificity that leads to severe side effects. Reasoning that T cells of the immune system are highly specific, we generated tumor-specific T cells by genetic modification of mouse primary T cells with a chimeric receptor reactive with the human breast cancer-associated Ag erbB-2. These T cells killed breast cancer cells and secreted IFN-gamma in an Ag-specific manner in vitro. We investigated their use against metastatic breast cancer in mice in an adjuvant setting, and compared their effectiveness with the commonly applied adjuvants doxorubicin, 5-fluorouracil, and herceptin. Mice were inoculated orthotopically with the human erbB-2-expressing spontaneously metastatic mouse breast cancer 4T1.2 in mammary tissue, and the primary tumor was surgically removed 8 days later., Significant metastatic disease was demonstrated in lung and liver at the time of surgery on day 8 with increased tumor burden at later time points. T cell adjuvant treatment of day 8 metastatic disease resulted in dramatic increases in survival of mice, and this survival was significantly greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin.
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This study has calculated the potential impact of hormone replacement therapy (HRT) on breast cancer incidence in Australia and has estimated how changes in prescribing HRT to women could affect this risk. The effects of HRT on breast cancer incidence was estimated using the attributable fraction technique with prevalence data derived from the 2001 Australian Health Survey and published rates of breast cancer relative risks from HRT use. In Australia, 12% of adult women were current HRT users and in 2001, 11783 breast cancers were reported. Of these, 1066 (9%) were potentially attributable to HRT. Restricting HRT use to women aged less than 65 years, ceasing HRT prescribing after 10 years or limiting combined oestrogen and progesterone HRT to five years (but otherwise keeping prescription levels to 2001 levels) may reduce the annual breast cancer caseload by 280 (2.4%), 555 (4.7%) or 674 (5.7%), respectively. In conclusion, this study has demonstrated that when HRT prevalence is relatively high, the effect on breast cancer incidence in the population will be significant. A small modification in HRT prescribing practices may impact breast cancer incidence in Australia with associated financial and health care provision implications. (C) 2005 Elsevier Ltd. All rights reserved.
Resumo:
Polysaccharides from the red alga Phacelocarpos peperocarpos were extracted with hot water, clarified, and precipitated with 2-propanol. The native preparation was highly sulfated (36.2% w/w). Alkali modification decreased the sulfate content by 2.0% w/w. The alkali-modified polysaccharide is composed mostly of galactose (Gal, 51 mol%) and 3,6-anhydrogalactose (AnGal, 41 mol%), with minor amounts of a mono-O-methylgalactose (MeGal, 1 mol%), xylose (Xyl, 6 mol%), and glucose (Glc, 1 mol%). The FTIR spectrum of the alkali-modified polysaccharide resembled K-carrageenan with absorption at 930 cm(-1) (indicative of AnGal) and 850 cm(-1) (Gal ii-sulfate). However, an additional, major band of absorption occurred at 820 cm(-1) indicating the presence of equatorial sulfate ester substitution at O-6 of Gal residues, A combination of linkage and C-13 NMR spectroscopic analyses showed that the polysaccharide was composed predominantly of a novel repeating-unit, O-beta-D-galactopyranosyl 4,6-disulfate)-(1 --> 4)-3,6-anhydro-alpha-D-galactopyranose. Minor structural variations also occurred, including alternative patterns of sulfation and the presence of terminal Xylp, The location of the terminal Xylp residues was not certain but evidence supported their attachment at O-3 of some 4-linked Galp residues. The cell-wall galactans remain unchanged during the life cycle of the alga. (C) 1996 Elsevier Science Ltd.
Resumo:
Stickiness is a major reason that limits the spray drying of various sugar-rich food products. Higher hygroscopicity of amorphous powder, increase in solubility of sugars with temperature, and lower melting point and glass transition temperature, contribute to the stickiness problem. So far, the glass transition temperature has been widely accepted as a best indicator for stickiness. There are various manoeuvres that have been applied to spray dry such products. Some of them are the addition of drying aids, modification of drier design and use of mild drying temperature conditions. This review paper highlights the major research works that deal with the stickiness property of sugar-rich foods.
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Field studies have shown that the elevation of the beach groundwater table varies with the tide and such variations affect significantly beach erosion or accretion. In this paper, we present a BEM (Boundary Element Method) model for simulating the tidal fluctuation of the beach groundwater table. The model solves the two-dimensional flow equation subject to free and moving boundary conditions, including the seepage dynamics at the beach face. The simulated seepage faces were found to agree with the predictions of a simple model (Turner, 1993). The advantage of the present model is, however, that it can be used with little modification to simulate more complicated cases, e.g., surface recharge from rainfall and drainage in the aquifer may be included (the latter is related to beach dewatering technique). The model also simulated well the field data of Nielsen (1990). In particular, the model replicated three distinct features of local water table fluctuations: steep rising phase versus flat falling phase, amplitude attenuation and phase lagging.
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We present an anisotropic correlated electron model on a periodic lattice, constructed from an R-matrix associated with the Temperley-Lieb algebra. By modification of the coupling of the first and last sites we obtain a model with quantum algebra invariance.
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Emotional accounts of startle modulation predict that startle is facilitated if elicited during aversive foreground stimuli. Attentional accounts hold that startle is enhanced if startle-eliciting stimulus and foreground stimulus are in the same modality. Visual and acoustic foreground stimuli and acoustic startle probes were employed in aversive differential conditioning and in a stimulus discrimination task. Differential conditioning was evident in electrodermal responses and blink latency shortening in both modalities, but effects on magnitude facilitation were found only for visual stimuli. In the discrimination task, skin conductance responses, blink latency shortening, and blink magnitude facilitation were larger during to-be-attended stimuli regardless of stimulus modality. The present results support the notion that attention and emotion can affect blink startle modulation during foreground stimuli.