Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide

Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions

Recruiting and retaining children and families' social workers. The potential of work discussion groups

Current difficulties with the recruitment and retention of children and families' social workers have been formally acknowledged. However, although initiatives which focus on remuneration and career progression are clearly welcome, research and evidence from practice highlights how social workers themselves place high value on the availability of good quality supervision. Yet, questions remain about whether first-line managers have the time or are even in the best position to offer this support. This article draws on the experience and evaluation of one particular model of supervision — 'work discussion groups' —and explores its impact with residential social work staff and teachers as well as the potential for further developments of this kind

Testing equality of variances in the analysis of repeated measurements

The problem of comparing the precisions of two instruments using repeated measurements can be cast as an extension of the Pitman-Morgan problem of testing equality of variances of a bivariate normal distribution. Hawkins (1981) decomposes the hypothesis of equal variances in this model into two subhypotheses for which simple tests exist. For the overall hypothesis he proposes to combine the tests of the subhypotheses using Fisher's method and empirically compares the component tests and their combination with the likelihood ratio test. In this paper an attempt is made to resolve some discrepancies and puzzling conclusions in Hawkins's study and to propose simple modifications.\ud \ud The new tests are compared to the tests discussed by Hawkins and to each other both in terms of the finite sample power (estimated by Monte Carlo simulation) and theoretically in terms of asymptotic relative efficiencies

Four dimensional Lie symmetry algebras and fourth order ordinary differential equations

Realizations of four dimensional Lie algebras as vector fields in the plane are explicitly constructed. Fourth order ordinary differential equations which admit such Lie symmetry algebras are derived. The route to their integration is described.Comment: 12 page

Evolutionary history of the ADRB2 gene in humans

No abstract available

Assessing the Privacy Risks of Data Sharing in Genomics

The protection of identity of participants in medical research has traditionally been guaranteed by the maintenance of the confidentiality of health information through mechanisms such as only releasing data in an aggregated form or after identifying variables have been removed. This protection of privacy is regarded as a fundamental principle of research ethics, through which the support of research participants and the public is maintained. Whilst this traditional model was adopted for genetics and genomics research, and was generally considered broadly fit for purpose, we argue that this approach is increasingly untenable in genomics. Privacy risk assessments need to have regard to the whole data environment, not merely the quality of the dataset to be released in isolation. As sources of data proliferate, issues of privacy protection are increasingly problematic in relation to the release of genomic data. However, we conclude that, by paying careful attention to potential pitfalls, scientific funders and researchers can take an important part in attempts to safeguard the public and ensure the continuation of potentially important scientific research

A Study of CO Emission in High Redshift QSOs Using the Owens Valley Millimeter Array

Searches for CO emission in high-redshift objects have traditionally suffered from the accuracy of optically-derived redshifts due to lack of bandwidth in correlators at radio observatories. This problem has motivated the creation of the new COBRA continuum correlator, with 4 GHz available bandwidth, at the Owens Valley Radio Observatory Millimeter Array. Presented here are the first scientific results from COBRA. We report detections of redshifted CO(J=3-2) emission in the QSOs SMM J04135+10277 and VCV J140955.5+562827, as well as a probable detection in RX J0911.4+0551. At redshifts of z=2.846, z=2.585, and z=2.796, we find integrated CO flux densities of 5.4 Jy km/s, 2.4 Jy km/s, and 2.9 Jy km/s for SMM J04135+10277, VCV J140955.5+562827, and RX J0911.4+0551, respectively, over linewidths of Delta(V_{FWHM}) ~ 350 km/s. These measurements, when corrected for gravitational lensing, correspond to molecular gas masses of order M(H_2) ~ 10^{9.6-11.1} solar masses, and are consistent with previous CO observations of high-redshift QSOs. We also report 3-sigma upper limits on CO(3-2) emission in the QSO LBQS 0018-0220 of 1.3 Jy km/s. We do not detect significant 3mm continuum emission from any of the QSOs, with the exception of a tentative (3-sigma) detection in RX J0911.4+0551 of S_{3mm}=0.92 mJy/beam.Comment: 18 pages, 5 figures, 2 tables, accepted to ApJ. Changes made for version 2: citations added, 2 objects added to Table 2 and Figure

The X-ray Properties of z>4 Quasars

We report on a search for X-ray emission from quasars with redshifts greater than four using the ROSAT public database. Our search has doubled the number of z>4 quasars detected in X-rays from 6 to 12. Most of those known prior to this work were radio-loud and X-ray selected sources; our study increases the number of X-ray detected, optically selected z>4 quasars from one to seven. We present their basic X-ray properties and compare these to those of lower redshift quasars. We do not find any evidence for strong broad-band spectral differences between optically selected z>4 quasars and those at lower redshifts.Comment: 7 pages, 4 figures included, LaTeX emulateapj.sty, accepted for publication in the Astronomical Journa

Development and evaluation of predictive models for measuring the biological integrity of streams

The ratio of the number of observed taxa to that expected to occur in the absence of human-caused stress (OIE) is an intuitive and ecologically meaningful measure of biological integrity. We examined how OIE ratios derived from stream invertebrate data varied among 234 unimpaired reference sites and 254 test sites potentially impaired by past logging. Data were collected from streams in three montane ecoregions in California. Two sets of River Invertebrate Prediction and Classification System (RIVPACS) predictive models were built: one set of models was based on near-species taxonomic resolution; the other was based on family identifications. Two models were built for each level of taxonomic resolution: one calculated 0 and E based on all taxa with probabilities of capture (PC) \u3e 0; the other calculated 0 and E based on only those taxa with PC2 0.5. Evaluations of the performance of each model were based on three criteria: (1) how well models predicted the taxa found at unimpaired sites, (2) the degree to which OIE values differed among unimpaired reference sites and potentially impaired test sites, and (3) the degree to which test site OIE values were correlated with independent measures of watershed alteration. Predictions of species models were more accurate than those of family models, and predictions of the PC2 0.5 species model were more robust than predictions of the PC2 0 model. OIE values derived from both species models were related to land use variables, but only assessments based on the PC2 0.5 model were insensitive to naturally occurring differences among streams, ecoregions, and year

Optimum anatomic socket position and sizing for the direct anterior approach: impingement and instability

© 2019 A comprehensive strategy is important for ensuring reproducible and safe acetabular component sizing and positioning. Presented here is our approach for anatomic acetabular component positioning in direct anterior total hip arthroplasty. This strategy has evolved with our understanding of the ramifications of socket sizing and positioning on instability and impingement. Data collected by a single surgeon (J.A.R.) between 2009 and 2011 influenced our current paradigm. We compare the sizing and positioning parameters of the anterior and posterior approach, thus demonstrating how the 2 are different. By highlighting these differences, we hope to provide a clear, defined approach to acetabular placement and sizing for direct anterior-approach total hip arthroplasty