Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?

The three-dimensional solution structure of the 40 residue amyloid beta-peptide, A beta(1-40), has been determined using NMR spectroscopy at pH 5.1, in aqueous sodium dodecyl sulfate (SDS) micelles, In this environment, which simulates to some extent a water-membrane medium, the peptide is unstructured between residues 1 and 14 which are mainly polar and likely solvated by water. However, the rest of the protein adopts an alpha-helical conformation between residues 15 and 36 with a kink or hinge at 25-27. This largely hydrophobic region is likely solvated by SDS. Based on the derived structures, evidence is provided in support of a possible new location for the transmembrane domain of A beta within the amyloid precursor protein (APP). Studies between pH 4.2 and 7.9 reveal a pH-dependent helix-coil conformational switch. At the lower pH values, where the carboxylate residues are protonated, the helix is uncharged, intact, and lipid-soluble. As the pH increases above 6.0, part of the helical region (15-24) becomes less structured, particularly near residues E22 and D23 where deprotonation appears to facilitate unwinding of the helix. This pH-dependent unfolding to a random coil conformation precedes any tendency of this peptide to aggregate to a beta-sheet as the pH increases. The structural biology described herein for A beta(1-40) suggests that (i) the C-terminal two-thirds of the peptide is an alpha-helix in membrane-like environments, (ii) deprotonation of two acidic amino acids in the helix promotes a helix-coil conformational transition that precedes aggregation, (iii) a mobile hinge exists in the helical region of A beta(1-40) and this may be relevant to its membrane-inserting properties and conformational rearrangements, and (iv) the location of the transmembrane domain of amyloid precursor proteins may be different from that accepted in the Literature. These results may provide new insight to the structural properties of amyloid beta-peptides of relevance to Alzheimer's disease.

Tailored advice on exercise - Does it make a difference?

Objectives: A controlled trial to compare the effectiveness of verbal advice from a family physician (FP) combined with either standard or tailored written information on physical activity in increasing the levels of physical activity in sedentary patients. Design: Sedentary patients (n = 763) were recruited through ten family practices and allocated to a control group or one of two intervention groups, Brief advice on physical activity was given by the FP during the consultation and either a standard or tailored pamphlet was mailed to the home address of patients assigned to the intervention groups within two days of their visit to the FP. Results: The response to follow-up, via a postal survey at one, six, and twelve months after the index consultation was 70%, 60%, and 57%, respectively. Treating all nonresponders as sedentary, the results revealed that although more tailored subjects reported some physical activity at each follow-up compared with the standard group, these differences were not significant, Furthermore, there was no significant difference in movement across the stages of readiness to exercise at follow-up between subjects in the tailored group who received material targeting their current stage (precontemplation or contemplation) and the standard group who received generic material that addressed both stages. Conclusion: These findings do not concur with the results from previous research in the areas of nutrition and smoking cessation where additional benefits were seen with a tailored intervention. Future research on the application of the principles of tailoring to the promotion of physical activity should focus on identifying which, if any, physical, social, psychological or environmental variables should be addressed to produce improved outcomes over and above the effects of well designed generic materials. (C) 1999 American Journal of Preventive Medicine.

Bioimpedance: Is it a predictor of true water volume?

Bioelectrical impedance analysis (BIA) has been reported to be insensitive to changes in water volumes in individual subjects, This study was designed to investigate the effect on the intra- and extracellular resistances (Ri and Re) of the segments of subjects for whom body water was changed without significant change to the total amount of electrolyte in the respective fluids, Twelve healthy adult subjects were recruited. Ri and Re of the leg, trunk, and arm of the subjects were determined from BIA measures prior to commencement of two separate studies that involved intervention, resulting in a loss/gain of body water effected either bt a sauna followed by water intake (study 1) or by ingestion (study 2). Ri and Re of the segments were also determined at a number of times following these interventions, The mean change in body water, expressed as a percentage of body weight, was 0.9% in study 1 and 1.25% in study 2. For each study, the results for each subject were normalized for each limb to the initial (prestudy) value and then the normalized results for each segment were pooled for all subjects, ANOVA of these pooled results failed to demonstrate any significant differences between the normalized mean values of Ri or Re of the segments measured through the course of each study, The failure to detect a change in Ri or Re is explained in terms of the basic theory of BIA.

Approach to designing rotating drum bioreactors for solid-state fermentation on the basis of dimensionless design factors

The development of large-scale solid-stale fermentation (SSF) processes is hampered by the lack of simple tools for the design of SSF bioreactors. The use of semifundamental mathematical models to design and operate SSF bioreactors can be complex. In this work, dimensionless design factors are used to predict the effects of scale and of operational variables on the performance of rotating drum bioreactors. The dimensionless design factor (DDF) is a ratio of the rate of heat generation to the rate of heat removal at the time of peak heat production. It can be used to predict maximum temperatures reached within the substrate bed for given operational variables. Alternatively, given the maximum temperature that can be tolerated during the fermentation, it can be used to explore the combinations of operating variables that prevent that temperature from being exceeded. Comparison of the predictions of the DDF approach with literature data for operation of rotating drums suggests that the DDF is a useful tool. The DDF approach was used to explore the consequences of three scale-up strategies on the required air flow rates and maximum temperatures achieved in the substrate bed as the bioreactor size was increased on the basis of geometric similarity. The first of these strategies was to maintain the superficial flow rate of the process air through the drum constant. The second was to maintain the ratio of volumes of air per volume of bioreactor constant. The third strategy was to adjust the air flow rate with increase in scale in such a manner as to maintain constant the maximum temperature attained in the substrate bed during the fermentation. (C) 2000 John Wiley & Sons, Inc.

The current status of psychological debriefing - It may do more harm than good

Despite the widespread use of psychological debriefing, serious concerns have been raised about its effectiveness and potential to do harm. 1 2 Psychological debriefing is broadly defined as a set of procedures including counselling and the giving of information aimed at preventing psychological morbidity and aiding recovery after a traumatic event. In 1995 Raphael and colleagues emphasised that there was an urgent need for reliable evidence from randomised controlled trials on the impact and worth of debriefing.3 Unfortunately, the news has not been good for debriefing. Debriefing is generally applied within the first few days after a traumatic event, lasts one to three hours, and usually includes procedures that encourage and normalise emotional expression. Debriefing can also be more narrowly defined in terms of the procedures used, the information provided and the target population. One example of this type of debriefing is known as critical incident stress debriefing.4

Humans, dogs and parasitic zoonoses - Unravelling the relationships in a remote endemic community in Northeast India using molecular tools

Canine parasitic zoonoses pose a continuing public health problem, especially in developing countries and communities that are socioeconomically disadvantaged. Our study combined the use of conventional and molecular epidemic, logical tools to determine the role of dogs in transmission of gastrointestinal (GI) parasites such as hookworms, Giardia and Ascaris in a parasite endemic teagrowing community in northeast India. A highly sensitive and specific molecular tool was developed to detect and differentiate the zoonotic species of canine hookworm eggs directly from faeces. This allowed epidemiological screening of canine hookworm species in this community to be conducted with ease and accuracy. The zoonotic potential of canine Giardia was also investigated by characterising Giardia duodenalis recovered from humans and dogs living in the same locality and households at three different loci. Phylogenetic and epidemiological analysis provided compelling evidence to support the zoonotic transmission of canine Giardia. Molecular tools were also used to identify the species of Ascaris egg present in over 30% of dog faecal samples. The results demonstrated the role of dogs as a significant disseminator and environmental contaminator of Ascaris lumbricoides in communities where promiscuous defecation practices exist. Our study demonstrated the usefulness of combining conventional and molecular parasitological and epidemiological tools to help solve unresolved relationships with regards to parasitic zoonoses.

Quantum technology: the second quantum revolution

We are currently in the midst of a second quantum revolution. The first quantum revolution gave us new rules that govern physical reality. The second quantum revolution will take these rules and use them to develop new technologies. In this review we discuss the principles upon which quantum technology is based and the tools required to develop it. We discuss a number of examples of research programs that could deliver quantum technologies in coming decades including: quantum information technology, quantum electromechanical systems, coherent quantum electronics, quantum optics and coherent matter technology.

Characterisation of the three-dimensional structure of earthworm burrow systems using image analysis and mathematical morphology

The aim of this work was to exemplify the specific contribution of both two- and three-dimensional (31)) X-ray computed tomography to characterise earthworm burrow systems. To achieve this purpose we used 3D mathematical morphology operators to characterise burrow systems resulting from the activity of an anecic (Aporrectodea noctunia), and an endogeic species (Allolobophora chlorotica), when both species were introduced either separately or together into artificial soil cores. Images of these soil cores were obtained using a medical X-ray tomography scanner. Three-dimensional reconstructions of burrow systems were obtained using a specifically developed segmentation algorithm. To study the differences between burrow systems, a set of classical tools of mathematical morphology (granulometries) were used. So-called granulometries based on different structuring elements clearly separated the different burrow systems. They enabled us to show that burrows made by the anecic species were fatter, longer, more vertical, more continuous but less sinuous than burrows of the endogeic species. The granulometry transform of the soil matrix showed that burrows made by A. nocturna were more evenly distributed than those of A. chlorotica. Although a good discrimination was possible when only one species was introduced into the soil cores, it was not possible to separate burrows of the two species from each other in cases where species were introduced into the same soil core. This limitation, partly due to the insufficient spatial resolution of the medical scanner, precluded the use of the morphological operators to study putative interactions between the two species.

Computational tools for the study of allergens

Allergy is a major cause of morbidity worldwide. The number of characterized allergens and related information is increasing rapidly creating demands for advanced information storage, retrieval and analysis. Bioinformatics provides useful tools for analysing allergens and these are complementary to traditional laboratory techniques for the study of allergens. Specific applications include structural analysis of allergens, identification of B- and T-cell epitopes, assessment of allergenicity and cross-reactivity, and genome analysis. In this paper, the most important bioinformatic tools and methods with relevance to the study of allergy have been reviewed.

Surface characterization of 6H-SiC (0001) substrates in indentation and abrasive machining

Surface characterization of 6H-SiC (0001) substrates in indentation and abrasive machining was carried out to investigate microfracture, residual damage, and surface roughness associated with material removal and surface generation. Brittle versus plastic deformation was studied using Vickers indention and nano-indentation. To characterize the abrasive machining response, the 6H-SiC (0001) substrates were ground using diamond wheels with grit sizes of 25, 15 and 7 mum, and then polished with diamond suspensions of 3 and 0.05 mum. It is found that in indentation, there was a scale effect for brittle versus plastic deformation in 6H-SiC substrates. Also, in grinding, the scales of fracture and surface roughness of the substrates decreased with a decrease in diamond grit size. However, in polishing, a reduction in grit size of diamond suspensions gave no significant improvement in surface roughness. Furthermore, the results showed that fracture-free 6H-SiC (0001) surfaces were generated in polishing with the existence of the residual crystal defects, which were associated with the origin of defects in single crystal growth. (C) 2003 Elsevier Ltd. All rights reserved.