5,180 research outputs found
Impact of three multimodal countrywide campaigns to promote hand hygiene in Belgian hospitals
Spectroscopic analysis of finite size effects around a Kondo quantum dot
We consider a simple setup in which a small quantum dot is strongly connected
to a finite size box. This box can be either a metallic box or a finite size
quantum wire.The formation of the Kondo screening cloud in the box strongly
depends on the ratio between the Kondo temperature and the box level spacing.
By weakly connecting two metallic reservoirs to the quantum dot, a detailed
spectroscopic analysis can be performed. Since the transport channels and the
screening channels are almost decoupled, such a setup allows an easier access
to the measure of finite-size effects associated with the finite extension of
the Kondo cloud.Comment: contribution to Les Houches proceeding, ``Quantum magnetism'' 200
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The human CTF4-orthologue AND-1 interacts with DNA polymerase α/primase via its unique C-terminal HMG box
A dynamic multi-protein assembly known as the replisome is responsible for DNA synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA helicase and DNA polymerase and recruits factors with roles in metabolic processes coupled to DNA replication. An important question in DNA replication is the extent to which the molecular architecture of the replisome is conserved between yeast and higher eukaryotes. Here we describe the biochemical basis for the interaction of the human CTF4-orthologue AND-1 with Pol α/primase, the replicative polymerase that
initiates DNA synthesis. AND-1 has maintained the trimeric structure of yeast Ctf4, driven by its conserved SepB domain. However, the primary interaction of AND-1 with Pol α/primase is mediated by its C-terminal HMG box, unique to mammalian AND-1, which binds the B subunit, at the same site targeted by the SV40 T antigen for viral replication. In addition, we report a novel DNA-binding activity in AND-1, which might promote the correct positioning of Pol α/primase on the lagging-strand template at the replication fork. Our findings provide a biochemical basis for the specific interaction between two critical components of the human replisome, and
indicate that important principles of replisome architecture have changed
significantly in evolution.This work was supported by a Wellcome Trust investigator award to L.P. (104641/Z/14/Z), a Cambridge Gates PhD scholarship to A.C.S., a PhD fellowship of the Boehringer-Ingelheim Fonds and awards from the Janggen-Pöhn-Stiftung and the Swiss National Science Foundation to S.H
Genetic background influences tumour development in heterozygous Men1 knockout mice
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1
The beta-Oslo method: experimentally constrained () reaction rates relevant to the -process
Unknown neutron-capture reaction rates remain a significant source of
uncertainty in state-of-the-art -process nucleosynthesis reaction network
calculations. As the -process involves highly neutron-rich nuclei for which
direct () cross-section measurements are virtually impossible,
indirect methods are called for to constrain () cross sections used
as input for the -process nuclear network. Here we discuss the newly
developed beta-Oslo method, which is capable of providing experimental input
for calculating () rates of neutron-rich nuclei. The beta-Oslo method
represents a first step towards constraining neutron-capture rates of
importance to the -process.Comment: 4 pages, 1 figure, conference proceedings Nuclei in the Cosmos XV
2018, Italy
An investigation of minimisation criteria
Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way
The Limits of Anthropocene Narratives
The rapidly growing transdisciplinary enthusiasm about developing new kinds of Anthropocene stories is based on the shared assumption that the Anthropocene predicament is best made sense of by narrative means. Against this assumption, this article argues that the challenge we are facing today does not merely lie in telling either scientific, socio-political, or entangled Anthropocene narratives to come to terms with our current condition. Instead, the challenge lies in coming to grips with how the stories we can tell in the Anthropocene relate to the radical novelty of the Anthropocene condition about which no stories can be told. What we need to find are meaningful ways to reconcile an inherited commitment to narrativization and the collapse of storytelling as a vehicle of understanding the Anthropocene as our current predicament
Individual repeatability of avian migration phenology: a systematic review and meta-analysis
Changes in phenology and distribution are being widely reported for many migratory species in response to shifting environmental conditions. Understanding these changes and the situations in which they occur can be aided by understanding consistent individual differences in phenology and distribution and the situations in which consistency varies in strength or detectability. Studies tracking the same individuals over consecutive years are increasingly reporting migratory timings to be a repeatable trait, suggesting that flexible individual responses to environmental conditions may contribute little to population-level changes in phenology and distribution. However, how this varies across species and sexes, across the annual cycle and in relation to study (tracking method, study design) and/or ecosystem characteristics is not yet clear. Here, we take advantage of the growing number of publications in movement ecology to perform a phylogenetic multilevel meta-analysis of repeatability estimates for avian migratory timings to investigate these questions. Of 2,433 reviewed studies, 54 contained suitable information for meta-analysis, resulting in 177 effect sizes from 47 species. Individual repeatability of avian migratory timings averaged 0.414 (95% confidence interval: 0.3-0.5) across landbirds, waterbirds and seabirds, suggesting consistent individual differences in migratory timings is a common feature of migratory systems. Timing of departure from the non-breeding grounds was more repeatable than timings of arrival at or departure from breeding grounds, suggesting that conditions encountered on migratory journeys and outcome of breeding attempts can influence individual variation. Population-level shifts in phenology could arise through individual timings changing with environmental conditions and/or through shifts in the numbers of individuals with different timings. Our findings suggest that, in addition to identifying the conditions associated with individual variation in phenology, exploring the causes of between-individual variation will be key in predicting future rates and directions of changes in migratory timings. We therefore encourage researchers to report the within- and between- individual variance components underpinning the reported repeatability estimates to aid interpretation of migration behaviour. In addition, the lack of studies in the tropics means that levels of repeatability in less strongly seasonal environments are not yet clear
Application of Portsmouth modification of physiological and operative severity scoring system for enumeration of morbidity and mortality (P-POSSUM) in pancreatic surgery
<p>Abstract</p> <p>Background</p> <p>Pancreatoduodenectomy (PD) is associated with high incidence of morbidity and mortality. We have applied P-POSSUM in predicting the incidence of outcome after PD to identify those who are at the highest risk of developing complications.</p> <p>Method</p> <p>A prospective database of 241 consecutive patients who had PD from January 2002 to September 2005 was retrospectively updated and analysed. P-POSSUM score was calculated for each patient and correlated with observed morbidity and mortality.</p> <p>Results</p> <p>30 days mortality was 7.8% and morbidity was 44.8%. Mean physiological score was 16.07 ± 3.30. Mean operative score was 13.67 ± 3.42. Mean operative score rose to 20.28 ± 2.52 for the complex major operation (p < 0.001) with 2 fold increase in morbidity and 3.5 fold increase in mortality. For groups of patients with a physiological score of (less than or equal to) 18, the O:P (observed to Predicted) morbidity ratio was 1.3–1.4 and, with a physiological score of >18, the O:P ratio was nearer to 1. Physiological score and white cell count were significant in a multivariate model.</p> <p>Conclusion</p> <p>P-POSSUM underestimated the mortality rate. While P-POSSUM analysis gave a truer prediction of morbidity, underestimation of morbidity and potential for systematic inaccuracy in prediction of complications at lower risk levels is a significant issue for pancreatic surgery</p
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