Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Sensitive Mother-to-Adolescent Disclosures After Divorce: Is the Experience of Sons Different From That of Daughters?

This study addressed two main questions: (a) Are adolescent sons and daughters exposed to sensitive maternal disclosures after divorce with similar frequency and in similar detail? and (b) Does gender act as a moderator in the association between maternal disclosures and adolescent adjustment difficulties? Forced-choice and open-ended data were collected from 194 adolescents within 2 years after their parents' divorce. Quantitative analyses revealed that although the majority of adolescents experience some level of maternal disclosure, neither frequency nor detail of maternal disclosure differed as a function of adolescent gender. Frequent and detailed maternal disclosures were associated with adolescent adjustment difficulties, primarily psychological distress. Gender did not moderate that significant association. Qualitative analysis shed light on the link between maternal disclosures and adolescent distress, suggested the importance of how disclosures are made, and revealed several gender differences in reactions to maternal disclosures. Implications of the findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery of gold cyanide using inherently conducting polymers

Removal of gold from basic solutions containing [Au(CN)₂]^? has been demonstrated using the inherently conducting polymer polypyrrole. Polymers containing sulfonated aromatic dopants have been found to display a significant ability to remove gold from such solutions. Experiments performed in solutions containing both gold and copper cyanide complexes indicate that the recovery process is not highly selective. However, the polypyrroles used display significantly faster rates of gold recovery than activated carbon. © 2003 Society of Chemical Industry     

Understanding the differences between how novice and experienced designers approach design tasks

Research was undertaken to understand how to provide the most appropriate support for novice designers in engineering design. However, how designers apply their experience and knowledge is not understood and further research in this area is required. This paper describes an observational study to understand how novice and experienced designers approach design tasks. Electronic Publication     

Detecting and characterising returns in a pulsed ladar system

A new multi-spectral laser radar (ladar) system based on the time-correlated single photon counting, time-of-flight technique has been designed to detect and characterise distributed targets at ranges of several kilometres. The system uses six separated laser channels in the visible and near infrared part of the electromagnetic spectrum. The authors present a method to detect the numbers, positions, heights and shape parameters of returns from this system, used for range profiling and target classification. The algorithm has two principal stages: non-parametric bump hunting based on an analysis of the smoothed derivatives of the photon count histogram in scale space, and maximum likelihood estimation using Poisson statistics. The approach is demonstrated on simulated and real data from a multi-spectral ladar system, showing that the return parameters can be estimated to a high degree of accuracy.     

Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

Electromagnetic scattering by a straight thin wire

The traveling-wave energy, which multiply diffracts on a straight thin wire, is represented as a sum of terms, each with a distinct physical meaning, that can be individually examined in the time domain. Expressions for each scattering mechanism on a straight thin wire are cast in the form of four basic electromagnetic wave concepts: diffraction, attachment, launch, and reflection. Using the basic mechanisms from P.Ya. Ufimtsev (1962), each of the scattering mechanisms is included into the total scattered field for the straight thin wire. Scattering as a function of angle and frequency is then compared to the moment-method solution. These analytic expressions are then extended to a lossy wire with a simple approximate modification using the propagation velocity on the wire as derived from the Sommerfeld wave on a straight lossy wire. Both the perfectly conducting and lossy wire solutions are compared to moment-method results, and excellent agreement is found. As is common with asymptotic solutions, when the electrical length of wire is smaller than 0.2 λ the results lose accuracy. The expressions modified to approximate the scattering for the lossy thin wire yield excellent agreement even for lossy wires where the wire radius is on the order of skin depth     

Choice With Initial and Terminal Link Reinforcement: An Alternative Self-Control Paradigm.

Self-control is demonstrated when a less desirable immediate outcome is chosen to ensure a substantially better future. In a novel animal analogue of this situation, primary reinforcement was delivered in both the initial and terminal links of a concurrent chain schedule. Rats made initial link choices between equal amounts of ethanol-free or ethanol-containing milk. Choosing the ethanol-free reinforcer resulted in delivery of the larger terminal link reinforcer and was thus analogous to self-control. Self-control decreased as the delay between initial and terminal links increased. The results have implications for human choice situations where decisions are made between two immediately available reinforcement alternatives each associated with a different delayed outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature

Cerebral hemodynamic changes in infants with progressive hydrocephalus have been studied with the transcranial Doppler (TCD) technique. Several authors have referred to the correlation between the hemodynamic changes and increased intracranial pressure (ICP). Despite conflicting conclusions on the value of pulsatility index (PI) and resistance index (RI) measurements for monitoring infantile hydrocephalus, these pulsatility indices are the most commonly used for this purpose. Although clinical signs of raised ICP are highly variable and unreliable in infants, assumptions have been made in most of the studies about the presence of elevated ICP on the basis of the patient's clinical state. Few studies have reported on actual ICP values, however, and a direct relationship between ICP and TCD changes has never been adequately demonstrated. In the present study, this relationship was investigated in long-term simultaneous TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring the effect of ICP on intracranial hemodynamics. Two groups of data sets were established. Group I consisted of pre- and postoperative (shunt implantation) TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings showing significant ICP variations. In most of the postoperative measurements there was a decrease in the average PI and RI values. The correlation between PI or RI and ICP in the long-term simultaneous recordings, however, was generally poor. The risk of obtaining false positive or false negative PI or RI values in short-term measurements was also demonstrated. It can be concluded from our results, besides the wide range of reference values for the Doppler indices and extracranial influences upon them, that the present Doppler indices are inadequate for monitoring the complex intracranial dynamic responses in patients with raised ICP.