27,287 research outputs found
Co-constructing a new framework for evaluating social innovation in marginalized rural areas
The EU funded H2020 project \u2018Social Innovation in Marginalised Rural Areas\u2019 (SIMRA; www.simra-h2020.eu) has the overall objective of advancing the state-of-the-art in social innovation. This paper outlines the process for co- developing an evaluation framework with stakeholders, drawn from across Europe and the Mediterranean area, in the fields of agriculture, forestry and rural development. Preliminary results show the importance of integrating process and outcome-oriented evaluations, and implementing participatory approaches in evaluation practice. They also raise critical issues related to the comparability of primary data in diverse regional contexts and highlight the need for mixed methods approaches in evaluation
Delivering reform in English healthcare: an ideational perspective
A variety of perspectives has been put forward to understand reform across healthcare systems. Recently, some have called for these perspectives to give greater recognition to the role of ideational processes. The purpose of this article is to present an ideational approach to understanding the delivery of healthcare reform. It draws on a case of English healthcare reform – the Next Stage Review led by Lord Darzi – to show how the delivery of its reform proposals was associated with four ideational frames. These frames built on the idea of “progress” in responding to existing problems; the idea of “prevailing policy” in forming part of a bricolage of ideas within institutional contexts; the idea of “prescription” as top-down structural change at odds with local contexts; and the idea of “professional disputes” in challenging the notion of clinical engagement across professional groups. The article discusses the implications of these ideas in furthering our understanding of policy change, conflict and continuity across healthcare settings
Investigating white matter fibre density and morphology using fixel-based analysis
Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order diffusion models, parameters related to fibre density can be extracted for individual fibre populations within each voxel (‘fixels’), and recent advances in statistics enable the multi-subject analysis of such data. However, investigating within-voxel microscopic fibre density alone does not account for macroscopic differences in the white matter morphology (e.g. the calibre of a fibre bundle). In this work, we introduce a novel method to investigate the latter, which we call fixel-based morphometry (FBM). To obtain a more complete measure related to the total number of white matter axons, information from both within-voxel microscopic fibre density and macroscopic morphology must be combined. We therefore present the FBM method as an integral piece within a comprehensive fixel-based analysis framework to investigate measures of fibre density, fibre-bundle morphology (cross-section), and a combined measure of fibre density and cross-section. We performed simulations to demonstrate the proposed measures using various transformations of a numerical fibre bundle phantom. Finally, we provide an example of such an analysis by comparing a clinical patient group to a healthy control group, which demonstrates that all three measures provide distinct and complementary information. By capturing information from both sources, the combined fibre density and cross-section measure is likely to be more sensitive to certain pathologies and more directly interpretable
Infrared composition of the Large Magellanic Cloud
The evolution of galaxies and the history of star formation in the Universe
are among the most important topics in today's astrophysics. Especially, the
role of small, irregular galaxies in the star-formation history of the Universe
is not yet clear. Using the data from the AKARI IRC survey of the Large
Magellanic Cloud at 3.2, 7, 11, 15, and 24 {\mu}m wavelengths, i.e., at the
mid- and near-infrared, we have constructed a multiwavelength catalog
containing data from a cross-correlation with a number of other databases at
different wavelengths. We present the separation of different classes of stars
in the LMC in color-color, and color-magnitude, diagrams, and analyze their
contribution to the total LMC flux, related to point sources at different
infrared wavelengths
Structure formation in active networks
Structure formation and constant reorganization of the actin cytoskeleton are
key requirements for the function of living cells. Here we show that a minimal
reconstituted system consisting of actin filaments, crosslinking molecules and
molecular-motor filaments exhibits a generic mechanism of structure formation,
characterized by a broad distribution of cluster sizes. We demonstrate that the
growth of the structures depends on the intricate balance between
crosslinker-induced stabilization and simultaneous destabilization by molecular
motors, a mechanism analogous to nucleation and growth in passive systems. We
also show that the intricate interplay between force generation, coarsening and
connectivity is responsible for the highly dynamic process of structure
formation in this heterogeneous active gel, and that these competing mechanisms
result in anomalous transport, reminiscent of intracellular dynamics
Simultaneous Extraction of the Fermi constant and PMNS matrix elements in the presence of a fourth generation
Several recent studies performed on constraints of a fourth generation of
quarks and leptons suffer from the ad-hoc assumption that 3 x 3 unitarity holds
for the first three generations in the neutrino sector. Only under this
assumption one is able to determine the Fermi constant G_F from the muon
lifetime measurement with the claimed precision of G_F = 1.16637 (1) x 10^-5
GeV^-2. We study how well G_F can be extracted within the framework of four
generations from leptonic and radiative mu and tau decays, as well as from K_l3
decays and leptonic decays of charged pions, and we discuss the role of lepton
universality tests in this context. We emphasize that constraints on a fourth
generation from quark and lepton flavour observables and from electroweak
precision observables can only be obtained in a consistent way if these three
sectors are considered simultaneously. In the combined fit to leptonic and
radiative mu and tau decays, K_l3 decays and leptonic decays of charged pions
we find a p-value of 2.6% for the fourth generation matrix element |U_{e 4}|=0
of the neutrino mixing matrix.Comment: 19 pages, 3 figures with 16 subfigures, references and text added
refering to earlier related work, figures and text in discussion section
added, results and conclusions unchange
The Relationship Between HR Practices and Firm Performance: Examining Causal Order
Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed
Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study
Peer reviewedPublisher PD
Epidemic space
The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)
Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1
Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases
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