1,301 research outputs found
TCO evaluation in physical asset management : benefits and limitations for industrial adoption
Part 1: Knowledge-Based Performance ImprovementInternational audienceNowadays, the evaluation of the total cost of ownership (TCO) of an asset for supporting informed decision-making both for investments and managerial issues within the asset management framework is gaining increasing attention in industry. Nevertheless its application in practice is still limited. The aim of this paper is to analyze the benefits and limitations of the adoption of TCO evaluation in asset management. Based on a literature review, the paper defines a framework that categorizes the benefits and potential applications that a TCO model can have for different stakeholders. Together with that, industry related issues that influence its implementation are also considered. Finally, empirical evidences are analyzed through a multiple case study to understand if those benefits are recognized in practice and which are the limitations for the practical adoption of a TCO model that should allow exploiting such benefits
Contrasting levels of absorption of intense femtosecond laser pulses by solids
The absorption of ultraintense, femtosecond laser pulses by a solid unleashes relativistic electrons, thereby creating a regime of relativistic optics. This has enabled exciting applications of relativistic particle beams and coherent X-ray radiation, and fundamental leaps in high energy density science and laboratory astrophysics. Obviously, central to these possibilities lies the basic problem of understanding and if possible, manipulating laser absorption. Surprisingly, the absorption of intense light largely remains an open question, despite the extensive variations in target and laser pulse structures. Moreover, there are only few experimental measurements of laser absorption carried out under very limited parameter ranges. Here we present an extensive investigation of absorption of intense 30 femtosecond laser pulses by solid metal targets. The study, performed under varying laser intensity and contrast ratio over four orders of magnitude, reveals a significant and non-intuitive dependence on these parameters. For contrast ratio of 10-9 and intensity of 2 Γ 1019W cm-2, three observations are revealed: preferential acceleration of electrons along the laser axis, a ponderomotive scaling of electron temperature, and red shifting of emitted second-harmonic. These point towards the role of J Γ B absorption mechanism at relativistic intensity. The experimental results are supported by particle-in-cell simulations
Filamins Regulate Cell Spreading and Initiation of Cell Migration
Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration
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Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of Ο-Oxidation
Peroxisomal fatty acid Ξ±-oxidation is an essential pathway for the degradation of Ξ²-carbon methylated fatty acids such as phytanic acid. One enzyme in this pathway is 2-hydroxyacyl CoA lyase (HACL1), which is responsible for the cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA. Hacl1 deficient mice do not present with a severe phenotype, unlike mice deficient in other Ξ±-oxidation enzymes such as phytanoyl-CoA hydroxylase deficiency (Refsum disease) in which neuropathy and ataxia are present. Tissues from wild-type and Hacl1β/β mice fed a high phytol diet were obtained for proteomic and lipidomic analysis. There was no phenotype observed in these mice. Liver, brain, and kidney tissues underwent trypsin digestion for untargeted proteomic liquid chromatography-mass spectrometry analysis, while liver tissues also underwent fatty acid hydrolysis, extraction, and derivatisation for fatty acid gas chromatography-mass spectrometry analysis. The liver fatty acid profile demonstrated an accumulation of phytanic and 2-hydroxyphytanic acid in the Hacl1β/β liver and significant decrease in heptadecanoic acid. The liver proteome showed a significant decrease in the abundance of Hacl1 and a significant increase in the abundance of proteins involved in PPAR signalling, peroxisome proliferation, and omega oxidation, particularly Cyp4a10 and Cyp4a14. In addition, the pathway associated with arachidonic acid metabolism was affected; Cyp2c55 was upregulated and Cyp4f14 and Cyp2b9 were downregulated. The kidney proteome revealed fewer significantly upregulated peroxisomal proteins and the brain proteome was not significantly different in Hacl1β/β mice. This study demonstrates the powerful insight brought by proteomic and metabolomic profiling of Hacl1β/β mice in better understanding disease mechanism in fatty acid Ξ±-oxidation disorders
Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of Ο-Oxidation
Peroxisomal fatty acid Ξ±-oxidation is an essential pathway for the degradation of Ξ²-carbon methylated fatty acids such as phytanic acid. One enzyme in this pathway is 2-hydroxyacyl CoA lyase (HACL1), which is responsible for the cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA. Hacl1 deficient mice do not present with a severe phenotype, unlike mice deficient in other Ξ±-oxidation enzymes such as phytanoyl-CoA hydroxylase deficiency (Refsum disease) in which neuropathy and ataxia are present. Tissues from wild-type and Hacl1β/β mice fed a high phytol diet were obtained for proteomic and lipidomic analysis. There was no phenotype observed in these mice. Liver, brain, and kidney tissues underwent trypsin digestion for untargeted proteomic liquid chromatography-mass spectrometry analysis, while liver tissues also underwent fatty acid hydrolysis, extraction, and derivatisation for fatty acid gas chromatography-mass spectrometry analysis. The liver fatty acid profile demonstrated an accumulation of phytanic and 2-hydroxyphytanic acid in the Hacl1β/β liver and significant decrease in heptadecanoic acid. The liver proteome showed a significant decrease in the abundance of Hacl1 and a significant increase in the abundance of proteins involved in PPAR signalling, peroxisome proliferation, and omega oxidation, particularly Cyp4a10 and Cyp4a14. In addition, the pathway associated with arachidonic acid metabolism was affected; Cyp2c55 was upregulated and Cyp4f14 and Cyp2b9 were downregulated. The kidney proteome revealed fewer significantly upregulated peroxisomal proteins and the brain proteome was not significantly different in Hacl1β/β mice. This study demonstrates the powerful insight brought by proteomic and metabolomic profiling of Hacl1β/β mice in better understanding disease mechanism in fatty acid Ξ±-oxidation disorders
Dynamical mean-field approach to materials with strong electronic correlations
We review recent results on the properties of materials with correlated
electrons obtained within the LDA+DMFT approach, a combination of a
conventional band structure approach based on the local density approximation
(LDA) and the dynamical mean-field theory (DMFT). The application to four
outstanding problems in this field is discussed: (i) we compute the full
valence band structure of the charge-transfer insulator NiO by explicitly
including the p-d hybridization, (ii) we explain the origin for the
simultaneously occuring metal-insulator transition and collapse of the magnetic
moment in MnO and Fe2O3, (iii) we describe a novel GGA+DMFT scheme in terms of
plane-wave pseudopotentials which allows us to compute the orbital order and
cooperative Jahn-Teller distortion in KCuF3 and LaMnO3, and (iv) we provide a
general explanation for the appearance of kinks in the effective dispersion of
correlated electrons in systems with a pronounced three-peak spectral function
without having to resort to the coupling of electrons to bosonic excitations.
These results provide a considerable progress in the fully microscopic
investigations of correlated electron materials.Comment: 24 pages, 14 figures, final version, submitted to Eur. Phys. J. for
publication in the Special Topics volume "Cooperative Phenomena in Solids:
Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom
Branch Mode Selection during Early Lung Development
Many organs of higher organisms, such as the vascular system, lung, kidney,
pancreas, liver and glands, are heavily branched structures. The branching
process during lung development has been studied in great detail and is
remarkably stereotyped. The branched tree is generated by the sequential,
non-random use of three geometrically simple modes of branching (domain
branching, planar and orthogonal bifurcation). While many regulatory components
and local interactions have been defined an integrated understanding of the
regulatory network that controls the branching process is lacking. We have
developed a deterministic, spatio-temporal differential-equation based model of
the core signaling network that governs lung branching morphogenesis. The model
focuses on the two key signaling factors that have been identified in
experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well
as the SHH receptor patched (Ptc). We show that the reported biochemical
interactions give rise to a Schnakenberg-type Turing patterning mechanisms that
allows us to reproduce experimental observations in wildtype and mutant mice.
The kinetic parameters as well as the domain shape are based on experimental
data where available. The developed model is robust to small absolute and large
relative changes in the parameter values. At the same time there is a strong
regulatory potential in that the switching between branching modes can be
achieved by targeted changes in the parameter values. We note that the sequence
of different branching events may also be the result of different growth
speeds: fast growth triggers lateral branching while slow growth favours
bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is
sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio
Binding Properties and Stability of the Ras-Association Domain of Rap1-GTP Interacting Adapter Molecule (RIAM)
The Rap1-GTP interacting adapter protein (RIAM) is an important protein in Rap1-mediated integrin activation. By binding to both Rap1 GTPase and talin, RIAM recruits talin to the cell membrane, thus facilitating talin-dependent integrin activation. In this article, we studied the role of the RIAM Ras-association (RA) and pleckstrin-homology (PH) domains in the interaction with Rap1. We found that the RA domain was sufficient for GTP-dependent interaction with Rap1B, and the addition of the PH domain did not change the binding affinity. We also detected GTP-independent interaction of Rap1B with the N-terminus of RIAM. In addition, we found that the PH domain stabilized the RA domain both in vitro and in cells
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