Solid-state 2H NMR study of methyl-d3-cobalamin

A solid-state 2H NMR study of methyl-d3-cobalamin has been performed as a function of temperature to provide information concerning the character and energetics of the motion performed by this unique bioorganometallic methyl group. Analysis of the 2H NMR line shape indicates that the methyl group undergoes rapid three-fold rotation, and that the Co-C-2H angle lies between 105.9 and 109.5 degrees. Determination of the spin-lattice relaxation times T1 shows that the relaxation is anisotropic, consistent with a "jumping" motion of the methyl group rather than rotational diffusion. This also provides the activation energy to methyl jumps as 8.3 +/- 1.3 kJ/mol. It is proposed that this energetic barrier may be a useful probe of changes in the electronic character of the Co-C bond that accompany the biological role of this molecule in such enzymes as methionine synthase.     

Auditory system plasticity in children after long periods of complete deafness

Separation and identification of proteins by two-dimensional (2-D) electrophoresis can be used for protein-based gene expression analysis. In this report single protein spots, from polyvinylidene difluoride blots of micropreparative E. coli 2-D gels, were rapidly and economically identified by matching their amino acid composition, estimated pI and molecular weight against all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2-D map were analyzed and identities assigned. Three of the proteins were unknown. By protein sequencing analysis, 20 of the 27 proteins were correctly identified. Importantly, correct identifications showed unambiguous "correct" score patterns. While incorrect protein identifications also showed distinctive score patterns, indicating that protein must be identified by other means. These techniques allow large-scale screening of the protein complement of simple organisms, or tissues in normal and disease states. The computer program described here is accessible via the World Wide Web at URL address (http:@expasy.hcuge.ch/).     

Induced candidosis in mice with artificially established oral flora

The aim of this study was to gauge the effect of an artificially established flora, unnatural for mice, on the induction of oral candidosis in mice. Four groups of BALB/c mice were compared; conventional Candida albicans-free mice, "germ-free" mice which had been inoculated with Candida-free human saliva, germ-free mice which had been exposed to a cocktail of Streptococcus mitis, S. sobrinus and S. sanguis, and uncontaminated germ-free mice. After exposure to C. albicans via drinking water, the four groups of mice were killed and their oral cavities examined for candidal growth and oral lesions. Conventional mice yielded significantly less candidal growth and exhibited significantly fewer oral lesions than the other three groups. Candidal lesions in the two groups of contaminated germ-free mice were significantly fewer than in the uncontaminated germ-free mice. The latter exhibited extensive candidal lesions with little inflammatory infiltrate. It is concluded that mice with human oral micro-organisms have some resistance against candidal infection albeit at a reduced level, that mice with natural oral flora are highly resistant, and that germ-free mice are extremely susceptible to C. albicans infection.     

Yearly stepwise increments of the growth hormone dose results in a better growth response after four years in girls with Turner syndrome. Dutch Working Group on Growth Hormone

To optimize the growth promoting effect of growth hormone (GH), 65 previously untreated girls with Turner syndrome (TS), chronological age (CA) 2-11 yr, were randomized into 3 dosage regimen groups: A, B, and C, with a daily recombinant-human GH dose during 4 study years of 4-4-4-4, 4-6-6-6, and 4-6-8-8 IU/m2 b.s. The first GH dosage increase in groups B and C resulted in a significantly higher mean height velocity (HV) compared with constant dose group A. During the third year, when the dose was raised again only in group C, mean HV was significantly higher in groups B and C than in group A, and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA (Dutch-Swedish-Danish Turner references) was identical; however, in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment, the following was determined. 1) The mean delta HSDSCA was significantly higher for groups B and C compared with group A, but not significantly different between groups B and C. 2) Although significantly higher compared with estimated values for untreated Dutch girls with TS, bone maturation of the GH treated girls was not significantly different between groups. 3) It was positively related with the degree of bone age (BA) retardation at start of study and negatively with baseline CA. 4) Both the modified Index of Potential Height (mIPHRUS) and a recently developed Turner-specific final height (FH) prediction method (PTSRUS), based on regression coefficients for H, CA, and bone age, showed significant increases in mean FH prediction, without significant differences between groups. PTSRUS values were markedly higher than the mIPHRUS values. Dose dependency could be shown for the area under the curve (AUC) for GH, but delta HSDSCA was not linearly related with AUC. Baseline GH binding protein (BP) levels were in 84% of the cases within the normal age range; the decrease in mean levels after 6 months GH was not significant. Mean insulin-like growth factor I (IGF-I) and IGFBP-3 plasma levels increased significantly, without significant differences between groups. delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period, beta-0.002 and beta-0.0004. Thus, a stepwise GH-dosing approach reduced the "waning" effect of the growth response after 4 yr treatment without undue bone maturation. FH prediction was not significantly different between treatment groups. Irrespective of the GH dose used, initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction, but was not statistically significant when expressed as delta HSDSCA over the study period.     

The use of coevolution and the artificial immune system for ensemble learning

This paper presents two new approaches for constructing an ensemble of neural networks (NN) using coevolution and the artificial immune system (AIS). These approaches are extensions of the CLONal Selection Algorithm for building ENSembles (CLONENS) algorithm. An explicit diversity promotion technique was added to CLONENS and a novel coevolutionary approach to build neural ensembles is introduced, whereby two populations representing the gates and the individual NN are coevolved. The former population is responsible for defining the ensemble size and selecting the members of the ensemble. This population is evolved using the differential evolution algorithm. The latter population supplies the best individuals for building the ensemble, which is evolved by AIS. Results show that it is possible to automatically define the ensemble size being also possible to find smaller ensembles with good generalization performance on the tested benchmark regression problems. More interestingly, the use of the diversity measure during the evolutionary process did not necessarily improve generalization. In this case, diverse ensembles may be found using only implicit diversity promotion techniques.     

Understanding the ways in which design features of educational websites impact upon student learning outcomes in blended learning environments

This study investigated the effectiveness, in terms of the attainment of relevant learning outcomes, of the types of learning promoted by educational features commonly incorporated in course management systems. Twenty-one courses with significant use of the Internet, but with face-to-face teaching as the predominant instructional mode, were investigated. Five hundred and ninety-five students taking these 21 courses completed a questionnaire which gave feedback on the extent of use of and quality of implementation of internet features, as well as their perception of the attainment of outcomes relating to approaches to learning, communication skills and understanding of content. A confirmatory factor analysis of scales pertinent to information presentation and constructive dialogue features showed a very poor fit to the data, indicating that the two types of function did not act in concert. Structural equation modelling was used to test instructional models in presage–process–product format for ‘information’ and ‘dialogue’ features. The information one showed a marginal fit to the data, but the dialogue one a very good fit. This shows that using the Internet for presenting information in a blended environment does not seem to effectively help students achieve learning outcomes. Using features which promote constructive dialogue and interactive learning activities encourages a deep approach to learning, the development of communication skills and enhanced understanding of content.     

Robust admissibility and admissibilisation of uncertain discrete singular time-delay systems

This paper is concerned with the characterisation of robust admissibility and admissibilisation for uncertain discrete-time singular system with interval time-varying delay. Considering the norm-bounded uncertainty and the interval time-varying delay, a new comparison model is introduced to transform the original singular system into two connected subsystems. After this transformation, a singular system without uncertainty and delay can be handled by the Lyapunov–Krasovskii functional method. By virtue of the scaled small gain theorem, an admissibility condition of the original singular system is proposed in terms of linear matrix inequalities. Moreover, the problem of robust admissibilisation of uncertain discrete singular time-varying system is also studied by iterative linear matrix inequality algorithm with initial condition optimisation. Several numerical examples are used to illustrate that the results are less conservative than existing ones.     

Containment control of multi-agent systems with unbounded communication delays

In this paper, we address the containment control problem for multi-agent systems under heterogeneous unbounded communication delays with emphasis on the convergence rate analysis. Different from most works on multi-agent systems, we resort to a viewpoint from the area of positive delay systems. We first cast the containment control problem into the stability analysis of an associated error system. In order to capture the convergence rate, we introduce a nondecreasing positive function whose reciprocal represents the decay rate of the associated error system. Under the assumption that each follower has access to at least one leader and some mild hypotheses on the communication delays, an explicit condition is given to characterise the decay rate of the associated error system in terms of linear programming. In addition, we provide several special cases when the communication delays are restricted by linear, sublinear and logarithmic growth rates, respectively. Finally, through numerical examples, it is shown that the convergence rate is dominated by the delays being the highest order infinitely large quantity.