822 research outputs found

    Semi-parametric estimation of the Wilshire creep life prediction model: an application to 2.25Cr-1Mo steel

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    The Wilshire equation is a recent addition to the literature on safe life prediction. While the effect of temperature on creep life is reasonably understood, the effect of stress isn’t. The Wilshire equation deals with this by partitioning over sub ranges of stress, but this approximation can lead to poor life time predictions. This paper introduces a semi-parametric procedure that allows the data itself to identify the stress relationship. When applied to 2.25Cr-1Mo steel it was found that the stress relationship is non-linear, and this semi-parametric version of the Wilshire model had better predictive performance compared to any partitioned Wilshire model. This approach contains a limit to valid extrapolation and the isothermal predictions for creep life have a more realistic pattern of behaviour

    The hand of Homo naledi

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    A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like wrist and palm indicate a significant degree of climbing, despite the derived nature of many aspects of the hand and other regions of the postcranial skeleton in H. naledi

    Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain

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    Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. Methodology/Principal Findings: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. Conclusions/Significance: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available

    Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

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    The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

    Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

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    Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

    Investigation of an Escherichia coli O145 outbreak in a child day-care centre - extensive sampling and characterization of eae- and stx1-positive E. coli yields epidemiological and socioeconomic insight

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    <p>Abstract</p> <p>Background</p> <p>On October 29<sup>th </sup>2009 the health authorities in the city of Trondheim, Norway were alerted about a case of Shiga toxin-positive <it>E. coli </it>(STEC) O145 in a child with bloody diarrhoea attending a day-care centre. Symptomatic children in this day-care centre were sampled, thereby identifying three more cases. This initiated an outbreak investigation.</p> <p>Methods</p> <p>A case was defined as a child attending the day-care centre, in whom <it>eae- </it>and <it>stx</it><sub>1</sub>- but not <it>stx</it><sub>2</sub>-positive <it>E. coli </it>O145:H28 was diagnosed from a faecal sample, with multilocus variable number of tandem repeat analysis (MLVA) profile identical to the index isolate. All 61 children, a staff of 14 in the day-care centre, and 74 close contacts submitted faecal samples. Staff and parents were interviewed about cases' exposure to foods and animals. Faecal samples from 31 ewes from a sheep herd to which the children were exposed were analyzed for <it>E. coli </it>O145.</p> <p>Results</p> <p>Sixteen cases were identified, from which nine presented diarrhoea but not haemolytic uremic syndrome (HUS). The attack rate was 0.26, and varied between age groups (0.13-0.40) and between the three day-care centre departments (0.20-0.50), and was significantly higher amongst the youngest children. Median duration of shedding was 20 days (0-71 days). Children were excluded from the day-care centre during shedding, requiring parents to take compassionate leave, estimated to be a minimum total of 406 days for all cases. Atypical enteropathogenic <it>E. coli </it>(aEPEC) were detected among 14 children other than cases. These isolates were genotypically different from the outbreak strain. Children in the day-care centre were exposed to faecal pollution from a sheep herd, but <it>E. coli </it>O145 was not detected in the sheep.</p> <p>Conclusions</p> <p>We report an outbreak of <it>stx</it><sub>1</sub>- and <it>eae-</it>positive STEC O145:H28 infection with mild symptoms among children in a day-care centre. Extensive sampling showed occurrence of the outbreak strain as well as other STEC and aEPEC strains in the outbreak population. MLVA-typing of the STEC-isolates strongly indicates a common source of infection. The study describes epidemiological aspects and socioeconomic consequences of a non-O157 STEC outbreak, which are less commonly reported than O157 outbreaks.</p

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  Όb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∌0) correlation that grows rapidly with increasing ÎŁETPb. A long-range “away-side” (Δϕ∌π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ÎŁETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁥2Δϕ modulation for all ÎŁETPb ranges and particle pT
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