134 research outputs found
Thermal Conductivity of Liquid Metals
Over the last decades, many experimental methods have been developed and improved to measure thermophysical properties of matter. This chapter gives an overview over the most common techniques to obtain thermal conductivity λ as a function of temperature T. These methods can be divided into steady state and transient methods. At the Institute of Experimental Physics at Graz University of Technology, an ohmic pulse-heating apparatus was installed in the 1980s, and has been further improved over the years, which allows the investigation of thermal conductivity and thermal diffusivity for the end of the solid phase and especially for the liquid phase of metals and alloys. This apparatus will be described in more detail. To determine thermal conductivity and thermal diffusivity with the ohmic pulse-heating method, the Wiedemann-Franz law is used. There are electronic as well as lattice contributions to thermal conductivity. As the materials examined at Graz University of Technology, are mostly in the liquid phase, the lattice contribution to thermal conductivity is negligibly small in most cases. Uncertainties for thermal conductivity for aluminum have been estimated ±6% in the solid phase and ±5% in the liquid phase
High-tech imaging and molecular biomarkers of fibrosis in hypertension-induced left ventricular hypertrophy
La hipertensión arterial (HTA) es el factor de riesgo cardiovascular más importante según la organización mundial de salud. La enfermedad cardiovascular (ECV) es la principal causa de mortalidad en todo el mundo, y representa 17 millones de muertes al año. Se estima que las complicaciones relacionadas con la HTA representan 9,4 millones de eventos cardiovasculares mortales por año. Aproximadamente la mitad de las muertes mundiales debidas a enfermedades cardíacas, accidentes cerebrovasculares e insuficiencia cardíaca se pueden atribuir a la HTA.
El sistema cardiovascular es sensible a los estimulantes fisiológicos y patológicos. La elevación de la presión arterial (PA) y el consiguiente estrés mecánico provocan cambios en el corazón y los vasos sanguíneos. La HTA es la causa más importante de sobrecarga de presión en el sistema cardiovascular. El principal mecanismo compensador para sobrecargar la sobrecarga en el corazón es la remodelación del tejido miocárdico. La remodelación cardíaca se acompaña de un aumento en la masa del ventrículo izquierdo (VI) y una hipertrofia concéntrica de las cámaras del miocardio, con alteraciones consecutivas en el tamaño, la forma, la estructura y el funcionamiento del corazón.
El crecimiento desproporcionado del ventrículo izquierdo involucra a todos los tipos de células cardíacas y está mediado por una serie compleja de estímulos mecánicos, neurohumorales, inflamatorios y oxidativos. Sin embargo, el estrés biomecánico relacionado con la carga hemodinámica mediada por HTA parece ser el elemento clave de la remodelación miocárdica. La adaptación del VI a la HTA en última instancia es la hipertrofia ventricular izquierda (HVI), el sello anatómico de la enfermedad cardíaca hipertensiva (ECH). La prevalencia de la ECH es alta, hasta el 60% de las personas con HTA no complicada tienen evidencia de aumento de la masa del VI en la ecocardiografía.
Un cambio en la forma o masa ventricular induce inevitablemente una alteración en las propiedades contráctiles y de relajación cardíacas. Por lo tanto, la HVI está directamente relacionada con la función cardíaca. La HVI también es un fuerte predictor independiente de supervivencia tanto en pacientes con enfermedad cardíaca previa como en la población general. De hecho, la HVI aumenta el riesgo de eventos cardiovasculares fatales y no fatales, que incluyen insuficiencia cardíaca, enfermedad coronaria, accidente cerebrovascular, arritmia y muerte súbita. La magnitud de los valores iniciales de la HVI determina la magnitud del riesgo cardiovascular de un individuo dado. Además, el tratamiento adecuado en pacientes con HVI ralentiza la progresión natural a la insuficiencia cardíaca y reduce la mortalidad posterior. En consecuencia, LVH es un predictor para la insuficiencia cardíaca y otros eventos cardíacos adversos. Es importante destacar que los pacientes con insuficiencia cardíaca generalmente progresan desde una fase asintomática (cuando la HVI ya podría estar presente) hasta las fases sintomáticas. Por lo tanto, es clínicamente relevante comprender las vías que conducen desde HTA a HVI, y la identificación temprana de estos individuos es obligatoria para iniciar o intensificar el tratamiento médico y, en consecuencia, reducir la morbilidad y la mortalidad.
El desarrollo de HVI involucra todos los tipos de células cardíacas, y conlleva un aumento de colágeno en el espacio intersticial cardíaco, denominado fibrosis cardíaca. Nuevas tecnologías en el campo de la cardiorresonancia magnética (CRM), incluyendo el análisis de strain (deformación miocárdica) y la cuantificación de fibrosis con mapeo T1, así como biomarcadores moleculares de fibrosis, podrían ayudar a identificar sujetos con HVI en un estadio precoz.
La hipótesis de la presente tesis fue que los parámetros de geometría, strain y fibrosis cardíaca derivados de la CMR están relacionados con la hemodinámica vascular y biomarcadores moleculares de fibrosis en pacientes hipertensos con HVI.
El objetivo principal de la presente tesis fue el siguiente: investigar la relación entre strain miocárdico y fibrosis cardíaca derivados de la CMR con biomarcadores moleculares de fibrosis en pacientes hipertensos con LVH.
Los objetivos secundarios fueron investigar la asociación entre la hemodinámica periférica con geometría, strain y fibrosis cardíaca derivados de la CMR y biomarcadores moleculares de fibrosis cardíaca; investigar la asociación entre la hemodinámica central con geometría, strain y fibrosis cardíaca derivados de la CMR y biomarcadores moleculares de fibrosis cardíaca; explorar los factores independientes asociados con strain miocárdico; explorar los factores independientes asociados con fibrosis cardíaca; investigar la asociación entre biomarcadores de estiramiento y daño miocárdico con geometría, strain y fibrosis cardíaca derivados de la CMR y biomarcadores moleculares de fibrosis cardíaca.
Se incluyeron a 46 pacientes hipertensos con HVI identificada por electrocardiograma, pero sin otra cardiopatía estructural. Se realizaron pruebas para la medición de parámetros de la hemodinámica periférica (presión arterial, monitorización ambulatoria de la presión arterial) y de la hemodinámica central (presión arterial central, velocidad de la onda de pulso). Así mismo, se realizó CMR con las técnicas SSFP y “feature tracking” para determinar los parámetros de strain, un determinante de la función cardíaca, así como la técnica “mapeo T1” para determinar la fracción de volumen extracelular (FVE), un determinador de la fibrosis cardíaca. Además, se determinaron biomarcadores de fibrosis (PICP, PIIINP, CITP, MMP-1) y de estiramiento y daño miocárdico (NT-proBNP, hs-Troponina T) en suero.
Para el análisis de asociación entre las variables disponibles se utilizaron la correlación de Pearson y modelos de regresión linear múltiple.
Los resultados principales y conclusiones fueron los siguientes:
La hemodinámica periférica se asoció con la masa ventricular y la función auricular.
La fibrosis cardíaca derivada de la CMR se relacionó con la geometría cardíaca y el strain: Un aumento de la fibrosis cardíaca se asoció a un aumento de las dimensiones cardíacas y una disminución del strain. La fibrosis cardíaca derivada de la CMR fue una componente relevante de cambios en la pared posterior del ventrículo izquierdo.
El strain miocárdico y los volúmenes cardíacos fueron directamente relacionados.
El strain radial se asoció inversamente con el volumen del ventrículo izquierdo al final de la sístole, un predictor de la contractilidad cardíaca.
El strain miocárdico se asoció con biomarcadores moleculares de fibrosis: Una reducción en strain longitudinal o circunferencial se relacionó con nivéles altos de CITP y con niveles bajos de MMP-1, respectivamente.
NT-proBNP y hs-Troponina T, biomarcadores establecidos de estiramiento y daño miocárdico, se asociaron con el grosor de la pared posterior del ventrículo izquierdo el diámetro de la aurícula izquierda.
En resumen, en hipertensos con HVI, las paredes del ventrículo izquierdo contienen una cantidad relevante de tejido fibroso identificado con CMR. La fibrosis miocárdica está asociada a una alteración de la deformidad miocárdica expresada en strain longitudinal, el cual a su vez está relacionado con biomarcadores moleculares de fibrosis. Además, cambios en la masa del ventrículo izquierdo, en el grosor de las paredes del ventrículo izquierdo, y en el diámetro de la aurícula izquierda modifican los niveles circulatorios de biomarcadores de estiramiento y daño miocárdico
Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.
The co-catabolism of multiple host-derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions. We applied metabolic flux analysis using stable isotopes and lipid fingerprinting to investigate the metabolic network of Mtb growing slowly in our steady-state chemostat system. We demonstrate that Mtb efficiently co-metabolises either cholesterol or glycerol, in combination with two-carbon generating substrates without any compartmentalisation of metabolism. We discovered that partitioning of flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle is the critical metabolic nodes which underlie the nutritional flexibility of Mtb. These findings provide novel insights into the metabolic architecture that affords adaptability of bacteria to divergent carbon substrates and expand our fundamental knowledge about the methyl citrate cycle and the glyoxylate shunt
Cohort profile: the Hortega Study for the evaluation of non-traditional risk factors of cardiometabolic and other chronic diseases in a general population from Spain.
PURPOSE: The Hortega Study is a prospective study, which investigates novel determinants of selected chronic conditions with an emphasis on cardiovascular health in a representative sample of a general population from Spain. PARTICIPANTS: In 1997, a mailed survey was sent to a random selection of public health system beneficiaries assigned to the University Hospital Rio Hortega's catchment area in Valladolid (Spain) (n=11 423, phase I), followed by a pilot examination in 1999-2000 of 495 phase I participants (phase II). In 2001-2003, the examination of 1502 individuals constituted the Hortega Study baseline examination visit (phase III, mean age 48.7 years, 49% men, 17% with obesity, 27% current smokers). Follow-up of phase III participants (also termed Hortega Follow-up Study) was obtained as of 30 November 2015 through review of health records (9.5% of participants without follow-up information). FINDINGS TO DATE: The Hortega Study integrates baseline information of traditional and non-traditional factors (metabolomic including lipidomic and oxidative stress metabolites, genetic variants and environmental factors, such as metals), with 14 years of follow-up for the assessment of mortality and incidence of chronic diseases. Preliminary analysis of time to event data shows that well-known cardiovascular risk factors are associated with cardiovascular incidence rates, which add robustness to our cohort. FUTURE PLANS: In 2020, we will review updated health and mortality records of this ongoing cohort for a 5-year follow-up extension. We will also re-examine elder survivors to evaluate specific aspects of ageing and conduct geolocation to study additional environmental exposures. Stored biological specimens are available for analysis of new biomarkers. The Hortega Study will, thus, enable the identification of novel factors based on time to event data, potentially contributing to the prevention and control of chronic diseases in ageing populations
LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.
The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. Methods: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. Results: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. Conclusions: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD
Perdeuteration of cholesterol for neutron scattering applications using recombinant Pichia pastoris
Deuteration of biomolecules has a great impact on both quality and scope of neutron scattering experiments. Cholesterol is a major component of mammalian cells, where it plays a critical role in membrane permeability, rigidity and dynamics, and contributes to specific membrane structures such as lipid rafts. Cholesterol is the main cargo in low and high-density lipoprotein complexes (i.e. LDL, HDL) and is directly implicated in several pathogenic conditions such as coronary artery disease which leads to 17 million deaths annually. Neutron scattering studies on membranes or lipid-protein complexes exploiting contrast variation have been limited by the lack of availability of fully deuterated biomolecules and especially perdeuterated cholesterol. The availability of perdeuterated cholesterol provides a unique way of probing the structural and dynamical properties of the lipoprotein complexes that underly many of these disease conditions. Here we describe a procedure for in vivo production of perdeuterated recombinant cholesterol in lipid-engineered Pichia pastoris. Using flask and fed-batch fermenter cultures in deuterated minimal medium perdeuteration of the purified cholesterol was verified by mass spectrometry and its use in a neutron scattering study was demonstrated using neutron reflectometry
The Socio-Economic Value of Natural Riverbanks in the Netherlands
Ecologists and economists both use a different approach to determine the value of nature. Its ecological value can be measured using criteria like rarity and diversity of species in an ecosystem. The economic value can be determined using non-market valuation techniques. This paper focuses on an empirical application of the Contingent Valuation Method (CVM) to find out whether this valuation method is a suitable method to estimate the economic value of natural riverbanks in the Netherlands. Natural riverbanks will provide habitat for species that particularly depend on the land water transit area. Since common riverbanks do not provide this habitat, natural river banks increase biodiversity in the Netherlands. On the basis of technical and ecological characteristics nine different types of natural riverbanks were distinguished. For each type a laymen description was made. This description served as a basis for economic valuation by means of CVM. The results of the CVM study shows that the average willingness to pay for non-use of a natural riverbank varied between 16 and 25 Dutch guilders per household year. The willingness to pay for recreational use ranged from 1,07 to 2,50 guilders per visit. The generated outcomes proved to be consistent with results from other studies. At first sight, the economic value of natural riverbanks seemed to be higher than their construction and maintenance cost
Emissions Trading, CDM, JI, and More - The Climate Strategy of the EU
The objective of this paper is to assess the likely allocation effects of the current cli-mate protection strategy as it is laid out in the National Allocation Plans (NAPs) for the European Emissions Trading Scheme (ETS). The multi-regional, multi-sectoral CGE-model DART is used to simulate the effects of the current policies in the year 2012 when the Kyoto targets need to be met. Different scenarios are simulated in or-der to highlight the effects of the grandfathering of permits to energy-intensive instal-lations, the use of the project-based mechanisms (CDM and JI), and the restriction imposed by the supplementarity criterion
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