995 resultados para Variables de surface


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Antibodies have the potential to be therapeutic reagents for malaria. Here we describe the production of a novel phage antibody display library against the C-terminal 19 kDa region of the Plasmodium yoelii YM merozoite surface protein-1 (MSP1(19)). In vivo studies against homologous lethal malaria challenge show an anti-parasite effect in a dose dependent manner, and analysis by plasmon resonance indicates binding to the antigen is comparable to the binding of a protective monoclonal antibody. The data support the lack of a need for any antibody Fc-related function and hold great significance for the development of a therapeutic reagent for malaria. (C) 2002 Elsevier Science Ltd. All rights reserved.

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Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP1(19) antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP1(19)-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP1(19)-specific CD4(+) T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP1(19)-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSPI,g-specific antibody response should greatly improve vaccine efficacy.

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Merozoite surface protein 1 (MSP1) of malaria parasites undergoes proteolytic processing at least twice before invasion into a new RBC. The 42-kDa fragment, a product of primary processing, is cleaved by proteolytic enzymes giving rise to MSP1(33), which is shed from the merozoite surface, and MSP1(19), which is the only fragment carried into a new RBC. In this study, we have identified T cell epitopes on MSP1(33) of Plasmodium yoelii and have examined their function in immunity to blood stage malaria. Peptides 20 aa in length, spanning the length of MSP1(33) and overlapping each other by 10 aa, were analyzed for their ability to induce T cell proliferation in immunized BALB/c and C57BL/6 mice. Multiple epitopes were recognized by these two strains of mice. Effector functions of the dominant epitopes were then investigated. Peptides Cm15 and Cm21 were of particular interest as they were able to induce effector T cells capable of delaying growth of lethal P. yoelii YM following adoptive transfer into immuno-deficient mice without inducing detectable Ab responses. Homologs of these epitopes could be candidates for inclusion in a subunit vaccine.

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Base metal resources are becoming more fine-grained and refractory and minerals separation processes require these ores to be milled to increasingly finer sizes. To cope with very fine grinding to below a P-80 of approximately 15 mum stirred milling technology has been adopted from other industries Neither this technology, nor the basic concepts of fine grinding, are well understood by the minerals processing industry. Laboratory studies were therefore carried out in order to investigate fine milling using different types of stirred mills. The variables analysed were stirrer speed, grinding media type and size, slurry solids content as well as the feed and product size. The results of the testwork have shown that all of these variables affect the grinding efficiency. The ratio of media size to material size was found to be of particular significance. The results were also analysed using the stress intensity approach and the optimum stress intensity ranges for the most efficient grinding were determined. Application of the results for process optimisation in the industrial size units is also discussed in this paper. (C) 2003 Elsevier Science Ltd. All rights reserved.

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Background. A study of postural stability was undertaken to identify the relationship between vision and support surface across age decades. Understanding when reliance on vision for postural stability emerges and the support conditions contributing to this instability may provide the evidence required to introduce falls-prevention strategies in younger age decades. Methods. We measured postural stability in 453 women aged 20 to 80 years using the Balance Master force-plate system while the women performed the modified Clinical Test for the Sensory Interaction and Balance (firm and foam surfaces, eyes open and closed) and the Single-Limb Stance Test (eyes open and closed). Results. Women in their 60s and 70s were more unstable than younger women in bilateral stance on a firm surface with the eyes closed. This instability was evident from the 50s when a foam surface was introduced and from the 40s when single-limb stance was tested with eyes closed. A further decline in stability was demonstrated for each subsequent decade when the eyes were closed in single-limb stance. Conclusions. Age, visual condition, and support surface were significant variables influencing postural stability in women. Reliance on vision for postural stability was evident for women from the 40s when single-limb stance was tested, from the 50s when bilateral stance on foam was tested, and from the 60s when a firm surface was used. The cause(s) of this decline in stability requires further investigation, and screening for postural instability between the ages of 40 and 60 is advocated.

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Background and Purpose. This study evaluated an electromyographic technique for the measurement of muscle activity of the deep cervical flexor (DCF) muscles. Electromyographic signals were detected from the DCF, sternocleidomastoid (SCM), and anterior scalene (AS) muscles during performance of the craniocervical flexion (CCF) test, which involves performing 5 stages of increasing craniocervical flexion range of motion-the anatomical action of the DCF muscles. Subjects. Ten volunteers without known pathology or impairment participated in this study. Methods. Root-mean-square (RMS) values were calculated for the DCF, SCM, and AS muscles during performance of the CCF test. Myoelectric signals were recorded from the DCF muscles using bipolar electrodes placed over the posterior oropharyngeal wall. Reliability estimates of normalized RMS values were obtained by evaluating intraclass correlation coefficients and the normalized standard error of the mean (SEM). Results. A linear relationship was evident between the amplitude of DCF muscle activity and the incremental stages of the CCF test (F=239.04, df=36, P<.0001). Normalized SEMs in the range 6.7% to 10.3% were obtained for the normalized RMS values for the DCF muscles, providing evidence of reliability for these variables. Discussion and Conclusion. This approach for obtaining a direct measure of the DCF muscles, which differs from those previously used, may be useful for the examination of these muscles in future electromyographic applications.

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Localization of signaling complexes to specific micro-domains coordinates signal transduction at the plasma membrane. Using immunogold electron microscopy of plasma membrane sheets coupled with spatial point pattern analysis, we have visualized morphologically featureless microdomains including lipid rafts, in situ and at high resolution. We find that an inner-plasma membrane lipid raft marker displays cholesterol-dependent clustering in microdomains with a mean diameter of 44 nm that occupy 35% of the cell surface. Cross-linking an outer-leaflet raft protein results in the redistribution of inner leaflet rafts, but they retain their modular structure. Analysis of Ras microlocalization shows that inactive H-ras is distributed between lipid rafts and a cholesterol-independent micro-domain. Conversely, activated H-ras and K-ras reside predominantly in nonoverlapping, cholesterol-independent microdomains. Galectin-1 stabilizes the association of activated H-ras with these nonraft microdomains, whereas K-ras clustering is supported by farnesylation, but not geranylgeranylation. These results illustrate that the inner plasma membrane comprises a complex mosaic of discrete microdomains. Differential spatial localization within this framework can likely account for the distinct signal outputs from the highly homologous Ras proteins.

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Improvement in analysis and reporting results of osteoarthritis (OA) clinical trials has been recently obtained because of harmonization and standardization of the selection of outcome variables (OMERACT 3 and OARSI). Moreover, OARSI has recently proposed the OARSI responder criteria. This composite index permits presentation of results of symptom modifying clinical trials in OA based on individual patient responses (responder yes/no). The 2 organizations (OMERACT and OARSI) established. a task force aimed at evaluating: (1) the variability of observed placebo and active treatment effects using the OARSI responder criteria; and (2) the possibility of proposing a simplified set of criteria. The conclusions of the task force were presented and discussed during the OMERACT 6 conference, where a simplified set of responder criteria (OMERACT-OARSI set of criteria) was proposed.

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The refinement calculus is a well-established theory for deriving program code from specifications. Recent research has extended the theory to handle timing requirements, as well as functional ones, and we have developed an interactive programming tool based on these extensions. Through a number of case studies completed using the tool, this paper explains how the tool helps the programmer by supporting the many forms of variables needed in the theory. These include simple state variables as in the untimed calculus, trace variables that model the evolution of properties over time, auxiliary variables that exist only to support formal reasoning, subroutine parameters, and variables shared between parallel processes.

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Viewed on a hydrodynamic scale, flames in experiments are often thin so that they may be described as gasdynamic discontinuities separating the dense cold fresh mixture from the light hot burned products. The original model of a flame as a gasdynamic discontinuity was due to Darrieus and to Landau. In addition to the fluid dynamical equations, the model consists of a flame speed relation describing the evolution of the discontinuity surface, and jump conditions across the surface which relate the fluid variables on the two sides of the surface. The Darrieus-Landau model predicts, in contrast to observations, that a uniformly propagating planar flame is absolutely unstable and that the strength of the instability grows with increasing perturbation wavenumber so that there is no high-wavenumber cutoff of the instability. The model was modified by Markstein to exhibit a high-wavenumber cutoff if a phenomenological constant in the model has an appropriate sign. Both models are postulated, rather than derived from first principles, and both ignore the flame structure, which depends on chemical kinetics and transport processes within the flame. At present, there are two models which have been derived, rather than postulated, and which are valid in two non-overlapping regions of parameter space. Sivashinsky derived a generalization of the Darrieus-Landau model which is valid for Lewis numbers (ratio of thermal diffusivity to mass diffusivity of the deficient reaction component) bounded away from unity. Matalon & Matkowsky derived a model valid for Lewis numbers close to unity. Each model has its own advantages and disadvantages. Under appropriate conditions the Matalon-Matkowsky model exhibits a high-wavenumber cutoff of the Darrieus-Landau instability. However, since the Lewis numbers considered lie too close to unity, the Matalon-Matkowsky model does not capture the pulsating instability. The Sivashinsky model does capture the pulsating instability, but does not exhibit its high-wavenumber cutoff. In this paper, we derive a model consisting of a new flame speed relation and new jump conditions, which is valid for arbitrary Lewis numbers. It captures the pulsating instability and exhibits the high-wavenumber cutoff of all instabilities. The flame speed relation includes the effect of short wavelengths, not previously considered, which leads to stabilizing transverse surface diffusion terms.

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The Crim1 gene is predicted to encode a transmembrane protein containing six von Willebrand-like cysteine-rich repeats (CRRs) similar to those in the BMP-binding antagonist Chordin (Chrd). In this study, we verify that CRIM1 is a glycosylated, Type I transmembrane protein and demonstrate that the extracellular CRR-containing domain can also be secreted, presumably via processing at the membrane. We have previously demonstrated Crim1 expression at sites consistent with an interaction with bone morphogenetic proteins (BMPs). Here we show that CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the protein and in so doing acts as an antagonist in three ways. CRIM1 binding of BMP4 and -7 occurs when these proteins are co-expressed within the Golgi compartment of the cell and leads to (i) a reduction in the production and processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell surface, and (iii) an effective reduction in the secretion of mature BMP. Functional antagonism was verified by examining the effect of coexpression of CRIM1 and BMP4 on metanephric explant culture. The presence of CRIM1 reduced the effective BMP4 concentration of the media, thereby acting as a BMP4 antagonist. Hence, CRIM1 modulates BMP activity by affecting its processing and delivery to the cell surface