2,987 research outputs found

    Tributyltin (TBT) and the decline of the Norfolk Broads

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    This is the final report to the Department for Environment, Food & Rural Affairs (DEFRA) on the contract "Tributyltin (TBT) and the decline of the Norfolk Broads"

    The Chiral Dipolar Hard Sphere Model

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    A simple molecular model of chiral molecules is presented in this paper : the chiral dipolar hard sphere model. The discriminatory interaction between enantiomers is represented by electrostatic (or magnetic) dipoles-dipoles interactions : short ranged steric repulsion are represented by hard sphere potential and, in each molecule, two point dipoles are located inside the sphere. The model is described in detail and some of its elementary properties are given ; in particular, it is shown that the that the knowledge of only three multipole spherical components (namely : Q10Q_{10}, Q21Q_{21} and Q22Q_{22}) allows to compute all multipole spherical components of the model. Despite, the simplicity of the model, it is shown also that the energy landscape of the interaction between two enantiomers is quite rich, this renders systems of chiral dipolar hard sphere very interesting and complicated to study. Few preliminary Monte Carlo simulation results are also reported in the paper. Last, but not least, this paper is dedicated to Jean-Jacques Weis.Comment: 28 pages, 14 Figures, 3 Tables. To appear in Molecular Physic

    Spatial and topological organization of DNA chains induced by gene co-localization

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    Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close-by. This is motivated by recurrent evidence that there exists physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on http://dx.doi.org/10.1371/journal.pcbi.100067

    Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

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    BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

    Pedigree analysis of Czech Holstein calves with schistosoma reflexum

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    <p>Abstract</p> <p>Background</p> <p>Schistosoma reflexum (SR) is congenital syndrome briefly characterized by visceral eventration, severe dorsoflexion and ankylosis of the spine and arthrogryposis. A genetic etiology has been proposed, but conclusive evidence has not yet been provided.</p> <p>Methods</p> <p>Pedigree analysis was carried out in 29 cases of SR in Czech Holsteins and Holstein crosses. Genetic relationship was evaluated and inbreeding coefficients calculated. Pedigrees of 15 Czech Holsteins fathering non-SR affected calves were used for comparison.</p> <p>Results</p> <p>Twenty-one cases occurred in one pedigree founded by three sires while three SR calves occurred in another pedigree with a common grandfather. The sex ratio between affected males and females was 11:6. Affected calves shared common ancestors different from those shared by the unaffected calves. The inbreeding coefficient in the SR affected calves was not increased compared to unaffected calves.</p> <p>Conclusions</p> <p>The findings are consistent with SR being inherited autosomal recessively. Further studies are however needed to confirm this and therefore a breeding trial is recommended where a suspected heterozygous sire is mated to closely related females.</p

    Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs

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    Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate hotspots, large igneous provinces and hence considerable dynamic topography. However, the active role of mantle plumes on subducting slabs remains poorly understood. Here we show that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau. Our findings are based on comparisons between 3D anisotropic tomography images and 3D petrological-thermo-mechanical models, which self-consistently explain several unique features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab (VSH4VSV) with thermo-mechanical calculations

    An instability criterion for nonlinear standing waves on nonzero backgrounds

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    A nonlinear Schr\"odinger equation with repulsive (defocusing) nonlinearity is considered. As an example, a system with a spatially varying coefficient of the nonlinear term is studied. The nonlinearity is chosen to be repelling except on a finite interval. Localized standing wave solutions on a non-zero background, e.g., dark solitons trapped by the inhomogeneity, are identified and studied. A novel instability criterion for such states is established through a topological argument. This allows instability to be determined quickly in many cases by considering simple geometric properties of the standing waves as viewed in the composite phase plane. Numerical calculations accompany the analytical results.Comment: 20 pages, 11 figure

    Sagittal jaw position in relation to body posture in adult humans – a rasterstereographic study

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    BACKGROUND: The correlations between the sagittal jaw position and the cranio – cervical inclination are described in literature. Only few studies focus on the sagittal jaw position and the body posture using valid and objective orthopaedic examination methods. The aim of this study was to test the hypothesis that patients with malocclusions reveal significant differences in body posture compared to those without (upper thoracic inclination, kyphotic angle, lordotic angle and lower lumbar inclination). METHODS: Eighty-four healthy adult patients (with a mean age = 25.6 years and ranging from 16.1 to 55.8 years) were examined with informed consent. The orthodontic examination horizontal overjet (distance between upper and lower incisors) was determined by using an orthodontic digital sliding calliper. The subjects were subdivided in respect of the overjet with the following results: 18 revealed a normal overjet (Class I), 38 had an increased overjet (Class II) and 28 had an reversed overjet (Class III). Rasterstereography was used to carry out a three – dimensional back shape analysis. This method is based on photogrammetry. A three-dimensional shape was produced by analysing the distortion of parallel horizontal white light lines projected on the patient's back, followed by mathematical modelling. On the basis of the sagittal profile the upper thoracic inclination, the thoracic angle, the lordotic angle and the pelvic inclination were determined with a reported accuracy of 2.8° and the correlations to the sagittal jaw position were calculated by means of ANOVA, Scheffé and Kruskal-Wallis procedures. RESULTS: Between the different overjet groups, no statistically significant differences or correlations regarding the analysed back shape parameters could be obtained. However, comparing males and females there were statistically significant differences in view of the parameters 'lordotic angle' and 'pelvic inclination'. CONCLUSION: No correlations between overjet and variables of the thoracic, lordotic or the pelvic inclination could be observed
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