1,260 research outputs found
A microstructure sensitive approach for the prediction of the creep behaviour and life under complex loading paths
International audienceThe prediction of the creep behaviour and life of components of aeronautic engines like high pressure turbine blades is still a challenging issue due to non-isothermal loadings. Indeed, certification procedures of turboshaft engines for helicopters consist of complex thermomechanical histories, sometimes including short and very high temperature excursions close to the γ'-solvus (T~1200°C) of the blade alloy. A better design of those components could be gained using a model that takes into account non-isothermal loadings inducing microstructural changes. Most of the commonly used models consider only a nearly constant (or slowly evolving) microstructure, i.e. far from the rapid microstructure evolutions encountered during close γ'-solvus overheatings where a rapid dissolution/precipitation of the γ'-phase and fast recovery mechanisms were observed by Cormier et al. (2007b). A new constitutive modelling approach was hence recently proposed in a crystal viscoplasticity framework to capture the transient effects of such rapid microstructure evolutions on the creep behaviour and life (Cormierand Cailletaud (2010a)). In this article, an updated version of this model is detailed. Special attention will be paid to (i) the effect of the accumulated plastic strain on the microstructure evolution, (ii) the introduction of an additional damage formulation, and (iii) the creep strain at failure. The performances of the model are illustrated on the basis of isothermal or complex non-isothermal creep experiments performed on nearly [001] oriented samples
A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination
Mutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. These phosphorylations stimulate the binding of the protein phosphatase PP2A-B56 to BRCA2 through a conserved binding motif. We show that the phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at sites of DNA damage and HR-mediated DNA repair. Moreover, we find that several cancer-associated mutations in BRCA2 deregulate the BRCA2-PP2A-B56 interaction and sensitize cells to PARP inhibition. Collectively, our work uncovers PP2A-B56 as a positive regulator of BRCA2 function in HR with clinical implications for BRCA2 and PP2A-B56 mutated cancers
Jet disc coupling in black hole binaries
In the last decade multi-wavelength observations have demonstrated the
importance of jets in the energy output of accreting black hole binaries. The
observed correlations between the presence of a jet and the state of the
accretion flow provide important information on the coupling between accretion
and ejection processes. After a brief review of the properties of black hole
binaries, I illustrate the connection between accretion and ejection through
two particularly interesting examples. First, an INTEGRAL observation of Cygnus
X-1 during a 'mini-' state transition reveals disc jet coupling on time scales
of orders of hours. Second, the black hole XTEJ1118+480 shows complex
correlations between the X-ray and optical emission. Those correlations are
interpreted in terms of coupling between disc and jet on time scales of seconds
or less. Those observations are discussed in the framework of current models.Comment: Invited talk at the Fifth Stromlo Symposium: Disks, Winds & Jets -
from Planets to Quasars. Accepted for publication in Astrophysics & Space
Scienc
Prior exercise training and experimental myocardial infarction: A systematic review and meta-analysis
Exercising prior to experimental infarction may have beneficial effects on the heart. The objective of this study was to analyze studies on animals that had exercised prior to myocardial infarction and to examine any benefits through a systematic review and meta-analysis. The databases MEDLINE, Google Scholar, and Cochrane were consulted. We analyzed articles published between January 1978 and November 2018. From a total of 858 articles, 13 manuscripts were selected in this review. When animals exercised before experimental infarction, there was a reduction in mortality, a reduction in infarct size, improvements in cardiac function, and a better molecular balance between genes and proteins that exhibit cardiac protective effects. Analyzing heart weight/body weight, we observed the following results - Mean difference 95% CI - -0.02 [-0.61,0.57]. Metaanalysis of the infarct size (% of the left ventricle) revealed a statistically significant decrease in the size of the infarction in animals that exercised before myocardial infarction, in comparison with the sedentary animals -5.05 [-7.68, -2.40]. Analysis of the ejection fraction, measured by echo (%), revealed that animals that exercised before myocardial infarction exhibited higher and statistically significant measures, compared with sedentary animals 8.77 [3.87,13.66]. We conclude that exercise performed prior to experimental myocardial infarction confers cardiac benefits to animals
Where words meet numbers:Comprehension of measurement unit terms in posterior cortical atrophy
Units of measurement (e.g., metre, week, gram) are critically important concepts in everyday life. Little is known about how knowledge of units is represented in the brain or how this relates to other forms of semantic knowledge. As unit terms are intimately connected with numerical quantity, we might expect knowledge for these concepts to be supported by parietally-mediated representations of space, time and magnitude. We investigated knowledge for measurement units in patients with posterior cortical atrophy (PCA), who display profound impairments of spatial and numerical cognition associated with occipital and parietal lobe atrophy. Relative to healthy controls, PCA patients displayed impairments for a range of unit-based knowledge, including the ability to specify the dimension which a unit refers to (e.g., grams measure mass), to select the appropriate units to measure everyday quantities (grams for sugar) and to determine the relative magnitudes of different unit terms (gram is smaller than kilogram). In most cases, their performance was also significantly poorer than a patient control group diagnosed with typical Alzheimer's disease. Our results suggest that impairment to systems that code numerical and spatial magnitudes has an effect on non-numerical verbal knowledge for measurement units. Units of measurement appear to lie at the intersection of the brain's verbal and numerical semantic systems, making them a critical class of concepts in which to investigate how magnitude-based codes contribute to verbal semantic representation
The Dyad Symmetry Element of Epstein-Barr Virus Is a Dominant but Dispensable Replication Origin
OriP, the latent origin of Epstein-Barr virus (EBV), consists of two essential elements: the dyad symmetry (DS) and the family of repeats (FR). The function of these elements has been predominantly analyzed in plasmids transfected into transformed cells. Here, we examined the molecular functions of DS in its native genomic context and at an ectopic position in the mini-EBV episome. Mini-EBV plasmids contain 41% of the EBV genome including all information required for the proliferation of human B cells. Both FR and DS function independently of their genomic context. We show that DS is the most active origin of replication present in the mini-EBV genome regardless of its location, and it is characterized by the binding of the origin recognition complex (ORC) allowing subsequent replication initiation. Surprisingly, the integrity of oriP is not required for the formation of the pre-replicative complex (pre-RC) at or near DS. In addition we show that initiation events occurring at sites other than the DS are also limited to once per cell cycle and that they are ORC-dependent. The deletion of DS increases initiation from alternative origins, which are normally used very infrequently in the mini-EBV genome. The sequence-independent distribution of ORC-binding, pre-RC-assembly, and initiation patterns indicates that a large number of silent origins are present in the mini-EBV genome. We conclude that, in mini-EBV genomes lacking the DS element, the absence of a strong ORC binding site results in an increase of ORC binding at dispersed sites
Expansion of Nature Conservation Areas: Problems with Natura 2000 Implementation in Poland?
In spite of widespread support from most member countries’ societies for European Union policy, including support for the sustainable development idea, in many EU countries the levels of acceptance of new environmental protection programmes have been and, in particular in new member states, still are considerably low. The experience of the countries which were the first to implement union directives show that they cannot be effectively applied without widespread public participation. The goal of this study was, using the example of Poland, to assess public acceptance of the expansion of nature conservation in the context of sustainable development principles and to discover whether existing nature governance should be modified when establishing new protected areas. The increase in protected areas in Poland has become a hotbed of numerous conflicts. In spite of the generally favourable attitudes to nature which Polish people generally have, Natura 2000 is perceived as an unnecessary additional conservation tool. Both local authorities and communities residing in the Natura areas think that the programme is a hindrance, rather than a help in the economic development of municipalities or regions, as was initially supposed. This lack of acceptance results from many factors, mainly social, historic and economic. The implications of these findings for current approach to the nature governance in Poland are discussed
Semantic Dementia: a specific network-opathy
Semantic dementia (SD) is a unique syndrome in the frontotemporal lobar degeneration spectrum. Typically presenting as a progressive, fluent anomic aphasia, SD is the paradigmatic disorder of semantic memory with a characteristic anatomical profile of asymmetric, selective antero-inferior temporal lobe atrophy. Histopathologically, most cases show a specific pattern of abnormal deposition of protein TDP-43. This relatively close clinical, anatomical and pathological correspondence suggests SD as a promising target for future therapeutic trials. Here, we discuss outstanding nosological and neurobiological challenges posed by the syndrome and propose a pathophysiological model of SD based on sequential, regionally determined disintegration of a vulnerable neural network
The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase
The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray
spectrometer, studied since 2015 for flying in the mid-30s on the Athena space
X-ray Observatory, a versatile observatory designed to address the Hot and
Energetic Universe science theme, selected in November 2013 by the Survey
Science Committee. Based on a large format array of Transition Edge Sensors
(TES), it aims to provide spatially resolved X-ray spectroscopy, with a
spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of
5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement
Review (SRR) in June 2022, at about the same time when ESA called for an
overall X-IFU redesign (including the X-IFU cryostat and the cooling chain),
due to an unanticipated cost overrun of Athena. In this paper, after
illustrating the breakthrough capabilities of the X-IFU, we describe the
instrument as presented at its SRR, browsing through all the subsystems and
associated requirements. We then show the instrument budgets, with a particular
emphasis on the anticipated budgets of some of its key performance parameters.
Finally we briefly discuss on the ongoing key technology demonstration
activities, the calibration and the activities foreseen in the X-IFU Instrument
Science Center, and touch on communication and outreach activities, the
consortium organisation, and finally on the life cycle assessment of X-IFU
aiming at minimising the environmental footprint, associated with the
development of the instrument. Thanks to the studies conducted so far on X-IFU,
it is expected that along the design-to-cost exercise requested by ESA, the
X-IFU will maintain flagship capabilities in spatially resolved high resolution
X-ray spectroscopy, enabling most of the original X-IFU related scientific
objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental
Astronomy with minor editin
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