304 research outputs found
Computing Branching Distances Using Quantitative Games
We lay out a general method for computing branching distances between labeled
transition systems. We translate the quantitative games used for defining these
distances to other, path-building games which are amenable to methods from the
theory of quantitative games. We then show for all common types of branching
distances how the resulting path-building games can be solved. In the end, we
achieve a method which can be used to compute all branching distances in the
linear-time--branching-time spectrum
Cement-in-cement stem revision for Vancouver type B periprosthetic femoral fractures after total hip arthroplasty: A 3-year follow-up of 23 cases
Background and purpose Revision surgery for periprosthetic femoral fractures around an unstable cemented femoral stem traditionally requires removal of existing cement. We propose a new technique whereby a well-fixed cement mantle can be retained in cases with simple fractures that can be reduced anatomically when a cemented revision is planned. This technique is well established in femoral stem revision, but not in association with a fracture
DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-α, ER-β and androgen receptor status
BACKGROUND: So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-α and ER-β, and the androgen receptor (AR). METHODS: In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas. RESULTS: In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status. CONCLUSION: DAX-1 might modify the AR and ER-β intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies
The Gaia-ESO Survey: Chromospheric Emission, Accretion Properties, and Rotation in Velorum and Chamaeleon I
We use the fundamental parameters delivered by the GES consortium in the first internal data release to select the members of Vel and Cha I among the UVES and GIRAFFE spectroscopic observations. A total of 140 Vel members and 74 Cha I members were studied. We calculated stellar luminosities through spectral energy distributions, while stellar masses were derived by comparison with evolutionary tracks. The spectral subtraction of low-activity and slowly rotating templates, which are rotationally broadened to match the of the targets, enabled us to measure the equivalent widths (EWs) and the fluxes in the H and H lines. The H line was also used for identifying accreting objects and for evaluating the mass accretion rate (). The distribution of for the members of Vel displays a peak at about 10 km s with a tail toward faster rotators. There is also some indication of a different distribution for the members of its two kinematical populations. Only a handful of stars in Vel display signatures of accretion, while many more accretors were detected in the younger Cha~I. Accreting and active stars occupy two different regions in a -flux diagram and we propose a criterion for distinguishing them. We derive in the ranges -yr and -yr for Vel and Cha I accretors, respectively. We find less scatter in the relation derived through the H EWs, when compared to the H diagnostics, in agreement with other authors
Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation
O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/- mice which have an increased level of O-GlcNAcylation, and found that Oga+/- mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/- mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.ope
Longitudinal Molecular Trajectories of Diffuse Glioma in Adults
The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear ¹² . Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of difuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specifc gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at diferent rates across the glioma subtypes, and hypermutation was not associated with diferences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner
A mutant O-GlcNAcase enriches Drosophila developmental regulators
YesProtein O-GlcNAcylation is a reversible post-translational modification of serines/threonines on
nucleocytoplasmic proteins. It is cycled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase
(O-GlcNAcase or OGA). Genetic approaches in model organisms have revealed that protein O-GlcNAcylation is
essential for early embryogenesis. Drosophila melanogaster OGT/supersex combs (sxc) is a polycomb gene,
null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities
of the O-GlcNAcylated proteins involved, and the underlying mechanisms linking these phenotypes to embryonic
development, are poorly understood. Identification of O-GlcNAcylated proteins from biological samples is
hampered by the low stoichiometry of this modification and limited enrichment tools. Using a catalytically inactive
bacterial O-GlcNAcase mutant as a substrate trap, we have enriched the O-GlcNAc proteome of the developing
Drosophila embryo, identifying, amongst others, known regulators of Hox genes as candidate conveyors of OGT
function during embryonic development.Wellcome Trust Investigator Award (110061); MRC grant (MC_UU_12016/5); and Royal Society Research Grant
Are Hox Genes Ancestrally Involved in Axial Patterning? Evidence from the Hydrozoan Clytia hemisphaerica (Cnidaria)
Background: The early evolution and diversification of Hox-related genes in eumetazoans has been the subject of conflicting hypotheses concerning the evolutionary conservation of their role in axial patterning and the pre-bilaterian origin of the Hox and ParaHox clusters. The diversification of Hox/ParaHox genes clearly predates the origin of bilaterians. However, the existence of a "Hox code' predating the cnidarian-bilaterian ancestor and supporting the deep homology of axes is more controversial. This assumption was mainly based on the interpretation of Hox expression data from the sea anemone, but growing evidence from other cnidarian taxa puts into question this hypothesis. Methodology/Principal Findings: Hox, ParaHox and Hox-related genes have been investigated here by phylogenetic analysis and in situ hybridisation in Clytia hemisphaerica, an hydrozoan species with medusa and polyp stages alternating in the life cycle. Our phylogenetic analyses do not support an origin of ParaHox and Hox genes by duplication of an ancestral ProtoHox cluster, and reveal a diversification of the cnidarian HOX9-14 genes into three groups called A, B, C. Among the 7 examined genes, only those belonging to the HOX9-14 and the CDX groups exhibit a restricted expression along the oralaboral axis during development and in the planula larva, while the others are expressed in very specialised areas at the medusa stage. Conclusions/Significance: Cross species comparison reveals a strong variability of gene expression along the oral-aboral axis and during the life cycle among cnidarian lineages. The most parsimonious interpretation is that the Hox code, collinearity and conservative role along the antero-posterior axis are bilaterian innovations
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