Search results for: Margarita S. Tikhonova

Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

Abstract:

In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

Procedia PDF Downloads 50

Authors: Ferentinos George, Papatheodorou George, Belmonte Genuario, Geraga Maria, Christodoulou Dimitris, Fakiris Elias, Iatrou Margarita, Kordella Stravroula, Prevenios Michail, Mentogianis Vassilis, Sotiropoulos Makis

Abstract:

The Ionian Sea Aquarium-Museum in Kefallinia Island, Greece and its twinning with that of Santa Maria al Bagno in the Salento peninsula, Italy, are recently established Hubs in the Ionian Sea funded by the European Territorial Cooperation Programme, Greece-Italy 2007-2013. The objectives of the Ionian Sea Aquarium-Museum are: (i) exhibiting to the public the underwater natural and cultural treasures of the seas surrounding the island, (ii) the functioning of a recreational/vocational hub for all educational levels but also for sea users and stakeholders, to raise their awareness of the seas and engage them in the European notion of the Blue Growth of the Seas and (iii) setting up diving parks in sites of natural and cultural importance. The natural heritage in the Aquarium-Museum is exhibited in five tanks displaying the two most important benthic habitats in the Mediterranean Sea, that is, the Posidonia oceanica and the Coralligene assemblages with the associated rich fauna. The cultural heritage is exhibited in: (i) Dioramas displaying scale model replicas of the three best preserved ancient and historic wrecks. -The Fiscardo Roman wreck dating between 1st cent B.C. and 2nd cent. A.D., which is one of the largest and best preserved in the Mediterranean Sea. -The HMS PERSEUS British submarine, which is known for the second deepest submarine escape from all sunken submarines in WW II, and -A wooden wreck, the Italian ship Alma probably, which was requisitioned by the German army and used for transporting supplies and ammunition. (ii) Documentaries: The first two present the complete story from launching to sinking of: the HMS PERSEUS British submarine, the SS Ardena which is associated with the Italian Aqui Division killed by the German forces in Kefallinia and made known from the book and film “Captain Corelli’s Mandolin” and the third documentary deals with the birth place of seafaring in the world, which took place in the Greek. Archipelago by Neanderthals and modern humans between 115 and 35 thousand years ago. The Aquarium-Museum starts from next year (a) educational programmes for schools and tourists to discover the natural and cultural treasures around Kefallinia island, (b) recreational/vocational holiday activities centered on eco-diving and get involved in mapping and monitoring NATURA 2000 sites around the island and thus actively engaged in the Blue Growth of the seas and (c) summer schools aimed at under/post-graduate students, who are interested in marine archaeology and geo-habitat mapping and are looking for a job in the sustainable management of the seas. The exhibition themes in the Aquarium-Museum as well as the recreational /vocational and educational activities are prepared by the Oceanus Net laboratories of Patras University and were selected after surveying the seafloor using the latest state of art sonar and camera technologies.

Keywords: aquarium-museum, cultural and natural treasures, ionian sea, Kefallinia Island

Procedia PDF Downloads 553

Authors: Margarita Dufresne

Abstract:

This study devoted to development TPS for small space re-usable launchers. We have used SIRIUS design for S1 prototype. Multiphysics coupling for hypersonic reactive flow and thermos-structural analysis with and without ablation is provided by -CCM+ and COMSOL Multiphysics and FASTRAN and ACE+. Flow around hypersonic flight vehicles is the interaction of multiple shocks and the interaction of shocks with boundary layers. These interactions can have a very strong impact on the aeroheating experienced by the flight vehicle. A real gas implies the existence of a gas in equilibrium, non-equilibrium. Mach number ranged from 5 to 10 for first stage flight.The goals of this effort are to provide validation of the iterative coupling of hypersonic physics models in STAR-CCM+ and FASTRAN with COMSOL Multiphysics and ACE+. COMSOL Multiphysics and ACE+ are used for thermal structure analysis to simulate Conjugate Heat Transfer, with Conduction, Free Convection and Radiation to simulate Heat Flux from hypersonic flow. The reactive simulations involve an air chemical model of five species: N, N2, NO, O and O2. Seventeen chemical reactions, involving dissociation and recombination probabilities calculation include in the Dunn/Kang mechanism. Forward reaction rate coefficients based on a modified Arrhenius equation are computed for each reaction. The algorithms employed to solve the reactive equations used the second-order numerical scheme is obtained by a “MUSCL” (Monotone Upstream-cantered Schemes for Conservation Laws) extrapolation process in the structured case. Coupled inviscid flux: AUSM+ flux-vector splitting The MUSCL third-order scheme in STAR-CCM+ provides third-order spatial accuracy, except in the vicinity of strong shocks, where, due to limiting, the spatial accuracy is reduced to second-order and provides improved (i.e., reduced) dissipation compared to the second-order discretization scheme. initial unstructured mesh is refined made using this initial pressure gradient technique for the shock/shock interaction test case. The suggested by NASA turbulence models are the K-Omega SST with a1 = 0.355 and QCR (quadratic) as the constitutive option. Specified k and omega explicitly in initial conditions and in regions – k = 1E-6 *Uinf^2 and omega = 5*Uinf/ (mean aerodynamic chord or characteristic length). We put into practice modelling tips for hypersonic flow as automatic coupled solver, adaptative mesh refinement to capture and refine shock front, using advancing Layer Mesher and larger prism layer thickness to capture shock front on blunt surfaces. The temperature range from 300K to 30 000 K and pressure between 1e-4 and 100 atm. FASTRAN and ACE+ are coupled to provide high-fidelity solution for hot hypersonic reactive flow and Conjugate Heat Transfer. The results of both approaches meet the CIRCA wind tunnel results.

Keywords: hypersonic, first stage, high speed compressible flow, shock wave, aerodynamic heating, conugate heat transfer, conduction, free convection, radiation, fastran, ace+, comsol multiphysics, star-ccm+, thermal protection system (tps), space launcher, wind tunnel

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