Effects of high-dose atorvastatin treatment in plasma proteome after an acute coronary syndrome

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Estudio de la Estenosis Aórtica Valvular desde un punto de vista proteómico

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Characterization of individualized proteomic profiles in ST-segment elevation and no ST-segment elevation acute coronary syndrome

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Hazards Analysis and Failure Modes and Effects Criticality Analysis (FMECA) of Four Concept Vehicle Propulsion Systems

The primary objective of this research effort is to identify failure modes and hazards associated with the concept vehicles and to perform functional hazard analyses (FHA) and failure modes and effects criticality analyses (FMECA) for each. Boeing also created a Fault Tree Analysis (FTA) for each of the concept vehicles, as the FTA contains the connectivity between systems and is an accepted, top-down method to analyze the safety of an air-vehicle. Conceptual design of notional powertrain configuration for each of four (4) NASA RVLT (Revolutionary Vertical Lift Technology) Concept Vehicles were developed in as much detail as was necessary to support the reliability and safety analysis for this project. Functional block diagrams from each of the conceptual powertrain configurations were created and used to order the FHA, FMECA, and FTA. Hazards were identified and the severity of each were categorized in the FHA for use in a follow-up FMECA. The FTA took inputs from the FMECA and the functional block diagrams to develop the connectivity and develop a quantitative architecture that could be used to perform sensitivity studies, as related to vehicle safety.Guidelines for reliability targets for both the air vehicle and the operation in the UAM (Urban Air Mobility) mission are discussed. An industry literature search was performed in order to assess gaps in existing government regulations and industry specifications. The industry literature search led to air-vehicle and operational reliability discussions, as related to Distributed Electric/Hybrid-Electric Propulsion (DE/HEP) system operating in the UAM role. A discussion of results and recommendations for future work is also provided

Metabolómica: una nueva herramienta para el estudio conjunto de la aterosclerosis y la estenosis aórtica degenerativa

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Valvular Aortic Stenosis: A Proteomic Insight

Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area

Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction

Acute myocardial infarction with ST-segment elevation (STEMI) initiates with intraluminal thrombosis and results in total occlusion of the coronary artery. To date, characterization of the coronary thrombus proteome in STEMI patients has not been yet accomplished. Therefore, we aimed to perform an in-depth proteomic characterization of the human coronary thrombus by means of three different approaches: 2-DE followed by mass spectrometry (MALDI MS/MS), 1-DE combined either with liquid chromatography coupled to mass spectrometry in a MALDI TOF/TOF (LC-MALDI-MS/MS), or in a LTQ-Orbitrap (LC-ESI-MS/MS). This approach allowed us to identify a total of 708 proteins in the thrombus. Expression in coronary thrombi (n=20) of 14 proteins was verified, and the expression of fibrin and 6 cell markers (platelets, monocytes, neutrophils, eosinophils, T-cells and B-cells) quantified by selected reaction monitoring (SRM). A positive correlation of 5 proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) with CD41 was found, pointing out the potential activation of a focal adhesion pathway within thrombus platelets. DIDO1 protein was found to correlate negatively with thrombus fibrin, and was found up-regulated in the plasma of these STEMI patients, which may constitute a starting point for further analyses in the search for biomarkers of thrombosis. BIOLOGICAL SIGNIFICANCE: The proteomic characterization of the human coronary thrombus may contribute to a better understanding of the mechanisms involved in acute coronary syndrome, and thus pave the road for the identification of new therapeutic targets that may help addressing this and other thrombotic diseases. A novel methodology to characterize thrombus composition and expression of a sub-group of proteins is hereby described, which allowed linking protein expression with cellular and ECM matrix composition of the thrombus. Five proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) co-express within the human coronary thrombus with CD41, pointing out the potential activation of a focal adhesion pathway within thrombus platelets during thrombus formation. Besides, the protein death-inducer obliterator 1, found to be expressed within the human coronary thrombus, has been proved to increase in the plasma of STEMI patients, which constitutes an important starting point for further analyses in the search for biomarkers of thrombosis.This work was supported by grants from the Instituto de Salud Carlos III (FIS PI070537, PI11/02239), Fondos Feder, Redes temáticas de Investigación Cooperativa en Salud (RD12/0042/ 0071, RD06/0014/1015), and Fundación para la Investigación Sanitaria de Castilla-La Mancha (FISCAM PI2008-08, PI2008-28, PI2008-52). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP). The CNIC is supported by the Spanish Ministerio de Economia y Competitividad and the Fundacion Pro-CNIC. We would like to thank Dr. Gloria Alvarez-Llamas for her kind suggestions for the manuscript; Gemma Barroso from Proteomic Unit, Hospital Nacional de Paraplejicos, for her help and dedication to this work, as well as Veronica Moral and Ana Gallardo from the same Unit, and TamaraSastre andCarmenBermudez for their technical support.S

Patrimonio geopaleontológico de los depósitos aluviales situados sobre la terraza +28 m del Jarama. Nuevos datos micropaleontológicos y cronológicos (Solar de la Real Fábrica de Paños de San Fernando de Henares)

Trabajo presentado en la Reunión de Arqueología Madrileña, celebrada en Alcalá de Henares el 20 y 21 de noviembre de 2014.[ES] Durante los trabajos de vigilancia de los movimientos de tierras asociados a la obra de la construcción de viviendas en el solar de la Real Fábrica de Paños (en adelante RFP) de San Fernando de Henares se documentaron materiales geológicos de edad miocena y cuaternaria con un contacto lateral dinámico entre ellos, constituido por una falla extensional de dirección norte-sur. En los niveles cuaternarios se registraron numerosos restos paleontológicos y algunas piezas de industria lítica. Según los estudios preliminares geomorfológicos y de macromamíferos (Tapias y Arango 2008; Yravedra et al. 2008; Dones et al. 2011) se asignó una cronología genérica de Pleistoceno Medio, confirmada por la datación obtenida por racemización de aminoácidos de un molar de Equus caballus (304 ka). En este trabajo se aportan nuevos datos a partir de la revisión y estudio de los restos de micromamíferos recuperados en la unidad 3. La presencia de Microtus brecciensis y M. arvalis en la base de los depósitos aluviales posibilita su adscripción cronológica al Pleistoceno Medio avanzado (MIS 8 o MIS 6).[EN] During the monitoring of the movements of land associated with the work of the construction of homes in the Solar of the Royal Factory of Cloths of San Fernando de Henares, some geological materials of Miocene and Quaternary age were documented. Numerous paleontological remains and some stone tools have been registered in these quaternary levels. According to geomorphological preliminary studies and macromammals (Tapias y Arango 2008; Yravedra et al. 2008; Dones et al. 2011) a generic Middle Pleistocene chronology was assigned. This was confirmed by the aminoacids racemization dating of Equus caballus molar (304 ka) This paper provides new data of the remains of micromammals recovered. The faunal assemblage, with Microtus brecciensis and M arvalis found at the base of the alluvial deposits, has allowed reviewing previous studies. It could be more specific on the geochronological and paleoenviromental contextualization of remains and materials that could be assigned to advanced Middle Pleistocene (MIS 8 or MIS 6).Peer reviewe

Aproximación a la patogenia de la aterosclerosis.Análisis del secretoma de arterias humanas sanas y con distintos grados de afección

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