1,581 research outputs found
Mandatory public benefit reporting as a basis for charity accountability: findings from England & Wales
Charitable status is inherently linked in many jurisdictions with the requirement that an entity must be established for public benefit. But, until recently the public benefit principle had relatively little impact on the operations of most established charities. However, in England and Wales, reforms linked to the Charities Act 2006 led to a new requirement for public benefit reporting in the trustees’ annual report (TAR) of every registered charity. This new narrative reporting requirement had the potential to affect the understanding of accountability by charities. The paper investigates the impact of that requirement through a study of over 1400 sets of charity reports and account
11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle
OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud
RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud
RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer IRS1 decreased and pThr Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud
CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer IRS1, increases pThr Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action
The development of incorporated structures for charities:a 100 year comparison of England and New Zealand
This article contrasts the emergence of two specific incorporated structures for non-profit organizations which came into being more than a century apart. We compare the ability for charities to form as “incorporated societies” under the New Zealand Incorporated Societies Act 1908 (effective from 1909), and to form as “charitable incorporated organizations” (CIOs), which were enacted in England and Wales under the Charities Act 2006 (effective from 2013). The article emphasizes the need for charitable non-profit organizations to incorporate for effective operation. This issue is rarely discussed, but the chosen legal form brings specific financial accounting obligations, affecting organizations’ accountability to third parties. Taking a comparative international history approach and drawing on a range of sources, we explore the socio-legal processes which led to the relevant legislation in each country. In particular, this diffusion study investigates why a specific corporate form for charitable non-profit organizations came into effect more than 100 years later in England as compared to New Zealand, with “place” emerging as the most significant comparative dimension
Creativity out of chaos
Creativity is said to be highly desired in post-modern and post-industrial organizations Creativity and anarchy on the one hand, and managerialism, on the other, can be seen as different forms of knowledge, two opposed ideals. In many organizational as well as societal reforms we currently observe it is the managerialist ideal that wins over the anarchic. In this paper, we wonder if people fear anarchy? We reflect on the possible reasons for the fear, and we also try to explain why we believe that anarchic organizing should not be avoided or feared
The Pan-STARRS Moving Object Processing System
We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern
software package that produces automatic asteroid discoveries and
identifications from catalogs of transient detections from next-generation
astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing
orbits from a synthetic but realistic population of asteroids whose
measurements were simulated for a Pan-STARRS4-class telescope. Additionally,
using a non-physical grid population, we demonstrate that MOPS can detect
populations of currently unknown objects such as interstellar asteroids.
MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope
despite differences in expected false detection rates, fill-factor loss and
relatively sparse observing cadence compared to a hypothetical Pan-STARRS4
telescope and survey. MOPS remains >99.5% efficient at detecting objects on a
single night but drops to 80% efficiency at producing orbits for objects
detected on multiple nights. This loss is primarily due to configurable MOPS
processing limits that are not yet tuned for the Pan-STARRS1 mission.
The core MOPS software package is the product of more than 15 person-years of
software development and incorporates countless additional years of effort in
third-party software to perform lower-level functions such as spatial searching
or orbit determination. We describe the high-level design of MOPS and essential
subcomponents, the suitability of MOPS for other survey programs, and suggest a
road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table
Mapping local structural perturbations in the native state of stefin B (cystatin B) under amyloid forming conditions
Unlike a number of amyloid-forming proteins, stefins, and in particular stefin B (cystatin B) form amyloids under conditions where the native state predominates. In order to trigger oligomerization processes, the stability of the protein needs to be compromised, favoring structural re-arrangement however, accelerating fibril formation is not a simple function of protein stability. We report here on how optimal conditions for amyloid formation lead to the destabilization of dimeric and tetrameric states of the protein in favor of the monomer. Small, highly localized structural changes can be mapped out that allow us to visualize directly areas of the protein which eventually become responsible for triggering amyloid formation. These regions of the protein overlap with the Cu (II)-binding sites which we identify here for the first time. We hypothesize that in vivo modulators of amyloid formation may act similarly to painstakingly optimized solvent conditions developed in vitro. We discuss these data in the light of current structural models of stefin B amyloid fibrils based on H-exchange data, where the detachment of the helical part and the extension of loops were observed
Analysis induced reduction of a polyelectrolyte
The polymer, poly(diallyldimethylammonium chloride) (PDDA), is shown to undergo chemical change via a reduction mechanism during X-ray analysis. Examination of the N 1s spectrum of PDDA shows a time dependence on the degree of reduction, together with clear amplification of the extent of reduction through the charge compensation system and X-ray irradiation
Boronic acids for functionalisation of commercial multi-layer graphitic material as an alternative to diazonium salts
A novel radical-based functionalisation strategy for the synthesis of functionalised commercially obtained plasma-synthesised multi-layer graphitic material (MLG) is presented herein. 4-(trifluoromethyl)phenyl boronic acid was utilised as a source of 4-(trifluoromethyl)phenyl radicals to covalently graft upon the graphitic surface of MLG. Such a methodology provides a convenient and safer route towards aryl radical generation, serving as a potential alternative to hazardous diazonium salt precusors. The structure and morphology of the functionalised MLG (Arf-MLG) has been characterised using XPS, Raman, TGA, XRD, SEM, TEM and BET techniques. The XPS quantitative data and Raman spectra provide evidence of successful covalent attachment of 4-(trifluoromethyl)phenyl groups to MLG
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