245 research outputs found
Investigation on reconstruction methods applied to 3D terahertz computed tomography
International audience3D terahertz computed tomography has been performed using a monochromatic millimeter wave imaging system coupled with an infrared temperature sensor. Three different reconstruction methods (standard back-projection algorithm and two iterative analysis) have been compared in order to reconstruct large size 3D objects. The quality (intensity, contrast and geometric preservation) of reconstructed cross-sectional images has been discussed together with the optimization of the number of projections. Final demonstration to real-life 3D objects has been processed to illustrate the potential of the reconstruction methods for applied terahertz tomography
Streaming instability of slime mold amoebae: An analytical model
During the aggregation of amoebae of the cellular slime mould Dictyostelium, the interaction of chemical waves of the signaling molecule cAMP with cAMP-directed cell movement causes the breakup of a uniform cell layer into branching patterns of cell streams. Recent numerical and experimental investigations emphasize the pivotal role of the cell-density dependence of the chemical wave speed for the occurrence of the streaming instability. A simple, analytically tractable, model of Dictyostelium aggregation is developed to test this idea. The interaction of cAMP waves with cAMP-directed cell movement is studied in the form of coupled dynamics of wave front geometries and cell density. Comparing the resulting explicit instability criterion and dispersion relation for cell streaming with the previous findings of model simulations and numerical stability analyses, a unifying interpretation of the streaming instability as a cAMP wave-driven chemotactic instability is proposed
Stochastic analysis of three-dimensional hydraulic conductivity upscaling in a heterogeneous tropical soil
[EN] Hydraulic conductivity (K) heterogeneity is seldom considered in geotechnical practice for the impossibility of sampling the entire area of interest and for the difficulty of accounting for scale effects. Stochastic three-dimensional K upscaling can tackle these two problems, and a workflow is described with an application in a tropical soil. The application shows that K heterogeneity can be incorporated in the daily practice of the geotechnical modeler while discussing the aspects to consider when performing the upscaling so that the upscaled models reproduce the average fluxes at the fine scale.The authors thank the financial support by the Brazilian National Council for Scientific and Technological Development (CNPq) (Project 401441/2014-8). The doctoral fellowship award to the first author by the Coordination of Improvement of Higher Level Personnel (CAPES) is gratefully acknowledged. The first author thanks the International Mobility Grant awarded by CNPq (200597/2015-9) and Santander mobility. The authors also thank DHI-WASI for providing a FEFLOW Software license.Almeida De-Godoy, V.; Zuquette, L.; Gómez-Hernández, JJ. (2018). Stochastic analysis of three-dimensional hydraulic conductivity upscaling in a heterogeneous tropical soil. Computers and Geotechnics. 100:174-187. https://doi.org/10.1016/j.compgeo.2018.03.004S17418710
Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with no clinical
biomarker. Aims of this study were to characterize a metabolic signature of ASD, and to
evaluate multi-platform analytical methodologies in order to develop predictive tools for
diagnosis and disease follow up.
Urines were analyzed using: 1H- and 1
H-13C-NMR-based approaches and LC-HRMS-based
approaches (ESI+ and ESI- on a HILIC and C18 chromatography column). Data tables
obtained from the six analytical modalities on a training set of 46 urines (22 autistic children
and 24 controls) were processed by multivariate analysis (OPLS-DA). Prediction of each of
these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic
children and 8 controls) and ROC curves. Thereafter, a data fusion block-scaling OPLS-DA
model was generated from the 6 best models obtained for each modality. This fused OPLSDA
model showed an enhanced performance (R
2Y(cum)=0.88, Q
2
(cum)=0.75) compared to
each analytical modality model, as well as a better predictive capacity (AUC=0.91, p-value
0.006). Metabolites that are most significantly different between autistic and control children
(p<0.05) are indoxyl sulfate, N-\u2329-Acetyl-L-arginine, methyl guanidine and
phenylacetylglutamine. This multi-modality approach has the potential to contribute to find
robust biomarkers and characterize a metabolic phenotype of the ASD population
Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology
Risk-Based Management of Contaminated Groundwater: The Role of Geologic Heterogeneity, Exposure and Cancer Risk in Determining the Performance of Aquifer Remediation
Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation
Stimulation of CD95/Fas/APO-1 results in the induction of both apoptotic and non-apoptotic signaling pathways. The processes regulating these two opposing pathways have not been thoroughly elucidated to date. In this study, using quantitative immunoblots, imaging, and mathematical modeling, we addressed the dynamics of the DED proteins of the death-inducing signaling complex (DISC), procaspase-8, and cellular FLICE inhibitory proteins (c-FLIPs) to the onset of CD95-mediated ERK1/2 and p38 mitogen-activated protein kinase (MAPK) activation. We found that CD95 DISC-induced caspase-8 activity is important for the initiation of ERK1/2 and p38 MAPK activation. The long c-FLIP isoform, c-FLIPL, and the short c-FLIP isoform, c-FLIPR, inhibited MAPK induction by blocking caspase-8 processing at the DISC. Furthermore, we built a mathematical model describing CD95 DISC-mediated MAPK activation and apoptosis. The model quantitatively defined the dynamics of DED proteins, procaspase-8, and c-FLIP, which lead to caspase-8 activation and induction of apoptotic and non-apoptotic signaling pathways. In conclusion, the combination of biochemical analysis with mathematical modeling provides evidence for an important role of caspase-8 in CD95-mediated activation of MAPKs, while c-FLIP exerts a regulatory function in this process
Fas/FasL-mediated apoptosis and inflammation are key features of acute human spinal cord injury: implications for translational, clinical application
The Fas/FasL system plays an important role in apoptosis, the inflammatory response and gliosis in a variety of neurologic disorders. A better understanding of these mechanisms could lead to effective therapeutic strategies following spinal cord injury (SCI). We explored these mechanisms by examining molecular changes in postmortem human spinal cord tissue from cases with acute and chronic SCI. Complementary studies were conducted using the in vivo Fejota™ clip compression model of SCI in Fas-deficient B6.MRL-Fas-lpr (lpr) and wild-type (Wt) mice to test Fas-mediated apoptosis, inflammation, gliosis and axonal degeneration by immunohistochemistry, Western blotting, gelatin zymography and ELISA with Mouse 32-plex cytokine/chemokine panel bead immunoassay. We report novel evidence that shows that Fas-mediated apoptosis of neurons and oligodendrocytes occurred in the injury epicenter in all cases of acute and subacute SCI and not in chronic SCI or in control cases. We also found significantly reduced apoptosis, expression of GFAP, NF-κB, p-IKappaB and iba1, increased number of CD4 positive T cells and MMP2 expression and reduced neurological dysfunction in lpr mice when compared with Wt mice after SCI. We found dramatically reduced inflammation and cytokines and chemokine expression in B6.MRL-Fas-lpr mice compared to Wt mice after SCI. In conclusion, we report multiple lines of evidence that Fas/FasL activation plays a pivotal role in mediating apoptosis, the inflammatory response and neurodegeneration after SCI, providing a compelling rationale for therapeutically targeting Fas in human SCI
Activation of the Fas/Fas ligand pathway in hypertensive renal disease in Dahl/Rapp rats
BACKGROUND: Hypertensive nephrosclerosis is the second most common cause of end-stage renal failure in the United States. The mechanism by which hypertension produces renal failure is incompletely understood. Recent evidence demonstrated that an unscheduled and inappropriate increase in apoptosis occurred in the Dahl/Rapp rat, an inbred strain of rat that uniformly develops hypertension and hypertensive nephrosclerosis; early correction of the hypertension prevents the renal injury. The present study examined the role of the Fas/FasL pathway in this process. METHODS: Young male Dahl/Rapp salt-sensitive (S) and Sprague-Dawley rats were fed diets that contained 0.3% or 8.0% NaCl diets. Kidneys were examined at days 7 and 21 of the study. RESULTS: An increase in Fas and FasL expression was observed in glomerular and tubular compartments of kidneys of hypertensive S rats, whereas dietary salt did not change expression of either of these molecules in normotensive Sprague-Dawley rats. Associated with this increase was cleavage of Bid and activation of caspase-8, the initiator caspase in this apoptotic pathway, by day 21 of the study. CONCLUSIONS: Augmented expression of apoptotic signaling by the Fas/FasL pathway occurred during development of end-stage renal failure in this model of hypertensive nephrosclerosis
Galectin-9 Controls CD40 Signaling through a Tim-3 Independent Mechanism and Redirects the Cytokine Profile of Pathogenic T Cells in Autoimmunity
While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its control. We demonstrated that CD40 is in fact several receptors occurring as constellations of differentially glycosylated forms of the protein that can sometimes form hybrid receptors with other proteins. An enticing area of autoimmunity is differential glycosylation of immune molecules leading to altered signaling. Galectins interact with carbohydrates on proteins to effect such signaling alterations. Studying autoimmune prone NOD and non-autoimmune BALB/c mice, here we reveal that in-vivo CD40 signals alter the glycosylation status of non-autoimmune derived CD4 T cells to resemble that of autoimmune derived CD4 T cells. Galectin-9 interacts with CD40 and, at higher concentrations, prevents CD40 induced proliferative responses of CD4loCD40+ effector T cells and induces cell death through a Tim-3 independent mechanism. Interestingly, galectin-9, at lower concentrations, alters the surface expression of CD3, CD4, and TCR, regulating access to those molecules and thereby redirects the inflammatory cytokine phenotype and CD3 induced proliferation of autoimmune CD4loCD40+ T cells. Understanding the dynamics of the CD40 receptor(s) and the impact of glycosylation status in immunity will gain insight into how to maintain useful CD40 signals while shutting down detrimental ones
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