Evidence for Novel Action at the Cell‐Binding Site of Human Angiogenin Revealed by Heteronuclear NMR Spectroscopy,in silico and in vivo Studies

A member of the ribonuclease A superfamily, human angiogenin (hAng) is a potent angiogenic factor. Heteronuclear NMR spectroscopy combined with induced‐fit docking revealed a dual binding mode for the most antiangiogenic compound of a series of ribofuranosyl pyrimidine nucleosides that strongly inhibit hAng's angiogenic activity in vivo. While modeling suggests the potential for simultaneous binding of the inhibitors at the active and cell‐binding sites, NMR studies indicate greater affinity for the cell‐binding site than for the active site. Additionally, molecular dynamics simulations at 100 ns confirmed the stability of binding at the cell‐binding site with the predicted protein–ligand interactions, in excellent agreement with the NMR data. This is the first time that a nucleoside inhibitor is reported to completely inhibit the angiogenic activity of hAng in vivo by exerting dual inhibitory activity on hAng, blocking both the entrance of hAng into the cell and its ribonucleolytic activity.     

Hyperthermostable mutants of Bacillus licheniformis {alpha}-amylase: multiple amino acid replacements and molecular modelling

We have identified previously two critical positions for thethermostability of the highly thermostable -amylase from Bacilluslicheniformis. We have now introduced all 19 possible aminoacid residues to these two positions, His 133 and Ala209. Themost favourable substitutions were to Ile and Val, respectively,which both increased the half-life of the enzyme at 80°Cby a factor of 3. At both positions a stabilizing effect ofhydrophobic residues was observed, although only in the caseof position 133 could a clear correlation be drawn between thehydrophobicity of the inserted amino acid and the gain in proteinstability. The construction of double mutants showed a cumulativeeffect of the most favourable and/or deleterious substitutions.Computer modelling was used to generate a 3-D structure of thewild-type protein and to model substitutions at position 209,which lies in the conserved (/ß)₈ barrel domain of-amylase; Ala209 would be located at the beginning of the thirdhelix of the barrel, in the bottom of a small cavity facingthe fourth helix. The model suggests that replacement by, forexample, a valine could fill this cavity and therefore increaseintra- and interhelical compactness and hydrophobic interactions.     

Comparaison de la fiabilité opérationnelle des modules optiques équipant les systémes à 34 Mbit/s de France télécom

The purpose of the joint research programme conducted by the CNET and Alcatel CIT on various France Telecom 34 Mbit/s multimode optical links (0.85 and 1.3 μm) is to assess their behaviour versus time, compare their operational reliability and the different types of optoelectronic components used. Traceability on the entire product life cycle was performed using a micro-computer data base. Data was recorded from the begin-ning (January 1985) until the end of the first quarter of 1990. Analysis of the results obtained has taken into account the influence of storage and the failure analyses carried out on rejected components. The results obtained on 0.85 μm optical transmit modules have been used to elaborate a modelling procedure for reliability predictions.     

The advantages of directly identifying continuous-time transfer function models in practical applications

The direct identification and estimation of continuous-time models from sampled data is now mature. This paper does not present any new methodology, nor does it compare the performance of existing methods. Its main aim is to discuss the advantages of direct, continuous-time model identification with the help of illustrative examples that are all based on real data from practical applications. Although the specific method of statistical parameter estimation is relatively unimportant in this regard, the latest and most sophisticated time domain identification algorithm that is freely available to the reader is used in these examples in order to ensure that the results reflect the best performance that can be achieved at this time by time-domain identification.     

Determinants of e-consumer productivity in product retrieval on a commercial website: An experimental approach

This article investigates what determines e-consumer productivity, in the specific case of product retrieval, on a commercial website. With a 2 × 2 × 2 factorial design on 292 participants, an online experiment reveals that productivity in product retrieval (measured in terms of effectiveness, efficiency, and time) relates to website design (e.g., abstraction level of labels, animation), user characteristics (e.g., Internet experience, product category familiarity, cognitive absorption), and situational characteristics (e.g., task nature). The results also confirm interactive effects among the type of strategy used, the nature of the task, and the website design. These findings have notable implications for both research and practice.     

THE INVERSE FLUIDIZATION AIRLIFT BIOREACTOR, PART I: HYDRODYNAMIC STUDIES

The inverse fiuidization airlift bioreactor offers a simple solution to the problem of handling shear sensitive cultures and/or systems requiring biofilm growth control. This unit combines in a single vessel the hydrodynamic behavior of concentric tube airlift aerators or contactors and liquid-solid fluidized beds. The effects of the diameter of the concentric tubes, liquid level, bed properties and gas flow rate on gas holdup, bed expansion and liquid circulation velocity were investigated in this study. The Zuber and Findlay relation (1965) gives satisfactory results for gas holdup. The inverse bed expansion can be predicted by the Richardson and Zaki correlation (1953). The liquid circulation velocity can be calculated using a mechanical energy balance