Selected models of HIV-induced neurological disease.
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Perforation of the vena cava or atrium is a serious complication of monitoring with a central venous catheter. We designed an in vitro model with a pulsating simulated membrane to evaluate a number of variables that could affect relative perforating potential of different types of central venous catheters. To determine the perforating potential of central venous catheters, we studied the effects of (1) the angle of incidence (n = 6) between catheter and simulated membrane; (2) catheter material (polyurethane and polyethylene); (3) make (manufacturer and model) (n = 6), with 3 catheters of each make tested; (4) design (n = 3 each: silicone rubber, open-ended, blunt-ended, and polyurethane pigtail); and (5) number of lumens (single, double, or triple). Each trial was repeated five times with each catheter that was tested. Perforation was significantly more likely when the angle of incidence between catheter and pulsating simulated membrane was greater than 40 degrees than when it was 40 degrees (P less than 0.05). Perforation was less likely with single-lumen than comparable French-sized double- and triple-lumen catheters; among single-lumen catheters, perforation required many more pulsations with a polyurethane than a polyethylene catheter (P less than 0.001). Perforation potential differed significantly among 6 makes of 7-French triple-lumen catheters (P less than 0.05). Compared with other materials or designs, silicone rubber or a pigtail tip decreased the perforation potential of catheters (P less than 0.001). These data offer additional objective information to consider when choosing and positioning central venous catheters.
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A 13 amino acid peptide corresponding to a potent BALB/c mouse T cell epitope of hen's egg lysozyme (HEL) was substituted singly at five sites in the d flagellin of Salmonella muenchen. The resulting chimeric proteins were unable to expand T cells capable of being stimulated by the HEL epitope and induced T cell populations which either failed to respond or responded at a low level to a normally highly stimulatory flagellin T cell epitope that was present in all chimeras. The results suggested that substitution of a T cell epitope in flagellin may alter the processing of the resulting immunogen.
A method is introduced that allows one to select, for a given property and compound, among several prediction methods the presumably best-performing scheme based on prediction errors evaluated for structurally similar compounds. The latter are selected through analysis of atom-centered fragments (ACFs) in accord with a k nearest neighbor procedure in the two-dimensional structural space. The approach is illustrated with seven estimation methods for the water solubility of organic compounds and a reference set of 1876 compounds with validated experimental values. The discussion includes a comparison with the similarity-based error correction as an alternative approach to improve the performance of prediction methods and an extension that enables an ad hoc specification of the application domain.
Using different stereoselective chemical and chemoenzymatic approaches we synthesized the chiral, Calpha-methylated alpha-amino acid L-(alphaMe)Nva with a short, linear side-chain. A set of terminally protected model peptides to the pentamer level containing either (alphaMe)Nva or Nva in combination with Ala and/or Aib was prepared using solution methods and characterized fully. Two (alphaMe)Nva peptides were also synthesized using side-chain hydrogenation of the corresponding Calpha-methyl, Calpha-allylglycine (Mag) peptides. A detailed solution and crystal-state conformational analysis based on FT-IR absorption, 1H NMR and X-ray diffraction techniques allowed us to define that: (i) (alphaMe)Nva is an effective beta-turn and 3(10)-helix former; and (ii) the relationship between (alphaMe)Nva chirality and the screw sense of the turn/helix formed is that typical of protein amino acids, i.e. L-(alphaMe)Nva induces the preferential formation of right-handed folded structures. In more general terms, this study reinforced previous conclusions that peptides based on alpha-amino acids with a Calpha-methyl substituent and a Calpha-linear alkyl substituent are characterized by a strong tendency to fold into turn and helical structures.
The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of eukaryotic POL II promoters, experimentally defined by a transcription start site (TSS). Access to promoter sequences is provided by pointers to positions in the corresponding genomes. Promoter evidence comes from conventional TSS mapping experiments for individual genes, or, starting from release 73, from mass genome annotation projects. Subsets of promoter sequences with customized 5' and 3' extensions can be downloaded from the EPD website. The focus of current development efforts is to reach complete promoter coverage for important model organisms as soon as possible. To speed up this process, a new class of preliminary promoter entries has been introduced as of release 83, which requires less stringent admission criteria. As part of a continuous integration process, new web-based interfaces have been developed, which allow joint analysis of promoter sequences with other bioinformatics resources developed by our group, in particular programs offered by the Signal Search Analysis Server, and gene expression data stored in the CleanEx database. EPD can be accessed at http://www.epd.isb-sib.ch.
The costs and benefits of parasite virulence are analysed in an evolutionarily stable strategy (ESS) model. Increased host mortality caused by disease (virulence) reduces a parasite's fitness by damaging its food supply. The fitness costs of high virulence may be offset by the benefits of increased transmission or ability to withstand the host's defences. It has been suggested that multiple infections lead to higher virulence because of competition among parasite strains within a host. A quantitative prediction is given for the ESS virulence rate as a function of the coefficient of relatedness among co-infecting strains. The prediction depends on the quantitative relation between the costs of virulence and the benefits of transmission or avoidance of host defences. The particular mechanisms by which parasites can increase their transmission or avoid host defences also have a key role in the evolution of virulence when there are multiple infections.
We present a mathematical formulation of a theory of language change. The theory is evolutionary in nature and has close analogies with theories of population genetics. The mathematical structure we construct similarly has correspondences with the Fisher-Wright model of population genetics, but there are significant differences. The continuous time formulation of the model is expressed in terms of a Fokker-Planck equation. This equation is exactly soluble in the case of a single speaker and can be investigated analytically in the case of multiple speakers who communicate equally with all other speakers and give their utterances equal weight. Whilst the stationary properties of this system have much in common with the single-speaker case, time-dependent properties are richer. In the particular case where linguistic forms can become extinct, we find that the presence of many speakers causes a two-stage relaxation, the first being a common marginal distribution that persists for a long time as a consequence of ultimate extinction being due to rare fluctuations.
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OBJECTIVES: To determine the relationships between physical and performance characteristics and level of skill in youth soccer players aged 12-16 years. METHODS: Anthropometry, maturity status, functional and sport-specific parameters were assessed in elite, sub-elite, and non-elite youth players in four age groups: U13 (n = 117), U14 (n = 136), U15 (n = 138) and U16 (n = 99). RESULTS: Multivariate analyses of covariance by age group with maturity status as the covariate showed that elite players scored better than the non-elite players on strength, flexibility, speed, aerobic endurance, anaerobic capacity and several technical skills (p<0.05). Stepwise discriminant analyses showed that running speed and technical skills were the most important characteristics in U13 and U14 players, while cardiorespiratory endurance was more important in U15 and U16 players. The results suggest that discriminating characteristics change with competitive age levels. CONCLUSIONS: Characteristics that discriminate youth soccer players vary by age group. Talent identification models should thus be dynamic and provide opportunities for changing parameters in a long-term developmental context.
The ability to identify potential neurotoxicants depends upon the characteristics of our test instruments. The neurotoxic properties of lead, methylmercury, polychlorinated biphenyls, and organic solvents would all have been detected at some dose level by tests in current use, provided that the doses were high enough and administered at an appropriate time such as during gestation. The adequacy of animal studies, particularly rodent studies, to predict intake levels at which human health can be protected is disappointing, however. It is unlikely that the use of advanced behavioral methodology would alleviate the apparent lack of sensitivity of the rodent model for many agents.
The various components required for individualising clinical drug dosage regimens are reviewed, including a study of 3 types of fitting procedures, 2 types of gentamicin pharmacokinetic model and the utility of D-optimal times for obtaining serum gentamicin concentrations. The combination of the current Bayesian fitting procedure, the kslope pharmacokinetic model [in which the elimination rate constant (kel) can change from dose to dose with changing creatinine clearance] and the explicit measurement of the assay error pattern yielded predictions of future serum gentamicin concentrations which were (a) slightly better than those found using weighted nonlinear least squares; (b) somewhat better than those found with Bayesian fitting and a fixed-kel model; (c) better than those found using the traditional linear regression fitting procedure and a fixed kel model. D-Optimally timed pairs of concentrations also predicted future concentrations at least as well, and more cost effectively.
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