Identification of the region of non-A beta component (NAC) of alzheimer's disease amyloid responsible for its aggregation and toxicity

The non-beta-amyloid (Aß) component of Alzheimer's disease amyloid (NAC) and its precursor a-synuclein have been linked to amyloidogenesis in several neurodegenerative diseases. NAC and a-synuclein both form ß-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic. We recently established that a peptide comprising residues 3±18 of NAC retains these properties. To pinpoint the exact region responsible we have carried out assays of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity was measured by the ability of fresh and aged peptides to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells. On immediate dissolution, or after ageing, the fragments NAC(8±18) and NAC(8±16) are toxic, whereas NAC(12±18), NAC(9±16) and NAC(8±15) are not. Circular dichroism indicates that none of the peptides displays ß-sheet structure; rather all remain random coil throughout 24 h. However, in acetonitrile, an organic solvent known to induce ß sheet, fragments NAC(8±18) and NAC(8±16) both form ß-sheet structure. Only NAC(8±18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. These findings indicate that residues 8±16 of NAC, equivalent to residues 68±76 in a-synuclein, comprise the region crucial for toxicity.

A precisely-dated lake-level rise marked by diatomite formation in northeastern Ireland

The intercorrelation of palaeoclimate events from various studies is often hindered by a lack of precise chronological control. Tephra isochrons can overcome this problem by providing direct site linkages. This paper outlines a study of Holocene peat and diatomite deposits that accumulated within the floodplain of Lough Neagh, Northern Ireland. The Icelandic Hekla 4 tephra has been identified at the base of diatomite deposits at a number of sites and provides firm dating evidence for a widespread flooding event in the area at ca. 2300 BC. The evidence is consistent with other studies in Ireland and elsewhere for increased wetness at this time. The results demonstrate that the terrestrial deposits around Lough Neagh contain an important record of Holocene lake-level change. Dendrochronological evidence from the Lough Neagh area provides additional information about lake-level fluctuations over the past two millennia.

The “re-socialization” of Gypsy women in the literacy courses aimed to the recipients of the Social Integration Revenue Policy of the Region of Madrid

This article studies the gender values that are promoted both in the literacy courses for gypsy women beneficiaries of the Social Integration Revenue Policy of the Region of Madrid and in the events that are organized for this group by public institutions and NGOs. The process of “socialization” that occurs in the educative groups for Gypsy women is focused on constructing an image of what it is to be a “Gypsy modern woman”. Through multiple mechanisms and discursive techniques a specific conception of gender equality is transmitted in these educative spaces. In addition to this, Gypsy women are continually urged to assume certain values and social practices (of gender identity, of "citizenship", of parenting, etc..), while an archetype of "Gypsy Woman" which condenses powerful stereotypes and prejudices about the "Gypsy culture" and the gender relations characteristics of this group is constructed.

Radiocarbon peat chronologies and environmental change

Raised bog peat deposits form important archives for reconstructing past changes in climate. Precise and reliable age models are of vital importance for interpreting such archives. We propose enhanced, Markov chain Monte Carlo based methods for obtaining age models from radiocarbon-dated peat cores, based on the assumption of piecewise linear accumulation. Included are automatic choice of sections, a measure of the goodness of fit and outlier downweighting. The approach is illustrated by using a peat core from the Netherlands.

SuperWASP-N extrasolar planet candidates between 18 <RA <21h

The SuperWASP-I (Wide Angle Search for Planets-I) instrument observed 6.7 million stars between 8 and 15mag from La Palma during the 2004 May-September season. Our transit-hunting algorithm selected 11626 objects from the 184442 stars within the RA (right ascension) range 18-21h. We describe our thorough selection procedure whereby catalogue information is exploited along with careful study of the SuperWASP data to filter out, as far as possible, transit mimics. We have identified 35 candidates which we recommend for follow-up observations.

Characterization of a ligand-attenuated binding site on glycoprotein IIb/IIIa

We describe an epitope on the platelet integrin, GPIIb/IIIa, identified by the monoclonal antibody, 4F8, which is attenuated by small-molecule GPIIb/IIIa ligands. 4F8 did not bind to the ligand binding pocket as it did not compete with a radiolabelled antagonist, H-3-SC-52012. This indicates that the 4F8 epitope behaves as a ligand-attenuated binding site (LABS). Ligand-induced attenuation of 4178 was an active process as it was prevented by pretreating platelets with cytochalasin D and reduced by prostaglandin E-1 or inhibition of protein kinase C. Disappearance of the epitope was required for full platelet activation as 4F8 prevented platelet aggregation without inhibiting fibrinogen binding. These results suggest a model where disappearance of the 4F8 epitope is a secondary event required for full

Imaging the cool stars in the interacting binaries AE Aqr, BV Cen and V426 Oph

It is well known that magnetic activity in late-type stars increases with increasing rotation rate. Using inversion techniques akin to medical imaging, the rotationally broadened profiles from such stars can be used to reconstruct `Doppler images' of the distribution of cool, dark starspots on their stellar surfaces. Interacting binaries, however, contain some of the most rapidly rotating late-type stars known and thus provide important tests of stellar dynamo models. Furthermore, magnetic activity is thought to play a key role in their evolution, behaviour and accretion dynamics. Despite this, we know comparatively little about the magnetic activity and its influence on such binaries. In this review we summarise the concepts behind indirect imaging of these systems, and present movies of the starspot distributions on the cool stars in some interacting binaries. We conclude with a look at the future opportunities that such studies may provide.

Asymmetric rhodium carbene insertion into the Si-H bond: identification of new dirhodium(II) carboxylate catalysts using parallel synthesis techniques

Decomposition of methyl 2-diazophenylacetate in the presence of silanes and a chiral dirhodium(11) catalyst results in Si-H insertion of the intermediate carbenoid with varying degrees of enantioselectivity. New chiral dirhodium(11) carboxylate catalysts were identified using solution phase parallel synthesis techniques. (C) 2003 Elsevier Science Ltd. All rights reserved.

Dynamic pricing model and algorithm for perishable products with fuzzy demand (ABS 2* Journal)

This paper studies the dynamic pricing problem of selling fixed stock of perishable items over a finite horizon, where the decision maker does not have the necessary historic data to estimate the distribution of uncertain demand, but has imprecise information about the quantity demand. We model this uncertainty using fuzzy variables. The dynamic pricing problem based on credibility theory is formulated using three fuzzy programming models, viz.: the fuzzy expected revenue maximization model, a-optimistic revenue maximization model, and credibility maximization model. Fuzzy simulations for functions with fuzzy parameters are given and embedded into a genetic algorithm to design a hybrid intelligent algorithm to solve these three models. Finally, a real-world example is presented to highlight the effectiveness of the developed model and algorithm.

Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers

Although cerebral palsy (CP) is the most common cause of motor deficiency in young children, it occurs in only 2 to 3 per 1000 live births. In order to monitor prevalence rates, especially within subgroups (birthweight, clinical type), it is necessary to study large populations. A network of CP surveys and registers was formed in 14 centres in eight countries across Europe. Differences in prevalence rates of CP in the centres prior to any work on harmonization of data are reported. The subsequent process to standardize the definition of CP, inclusion/exclusion criteria, classification, and description of children with CP is outlined. The consensus that was reached on these issues will make it possible to monitor trends in CP rate, to provide a framework for collaborative research, and a basis for services planning among European countries.