Neocortical hyperexcitability defect in a mutant mouse model of spike-wave epilepsy, {\it stargazer}

Single-locus mutations in mice can express epileptic phenotypes and provide critical insights into the naturally occurring defects that alter excitability and mediate synchronization in the central nervous system (CNS). One such recessive mutation (on chromosome (Chr) 15), stargazer(stg/stg) expresses frequent bilateral 6-7 cycles per second (c/sec) spike-wave seizures associated with behavioral arrest, and provides a valuable opportunity to examine the inherited lesion associated with spike-wave synchronization.^ The existence of distinct and heterogeneous defects mediating spike-wave discharge (SWD) generation has been demonstrated by the presence of multiple genetic loci expressing generalized spike-wave activity and the differential effects of pharmacological agents on SWDs in different spike-wave epilepsy models. Attempts at understanding the different basic mechanisms underlying spike-wave synchronization have focused on $\gamma$-aminobutyric acid (GABA) receptor-, low threshold T-type Ca$\sp{2+}$ channel-, and N-methyl-D-aspartate receptor (NMDA-R)-mediated transmission. It is believed that defects in these modes of transmission can mediate the conversion of normal oscillations in a trisynaptic circuit, which includes the neocortex, reticular nucleus and thalamus, into spike-wave activity. However, the underlying lesions involved in spike-wave synchronization have not been clearly identified.^ The purpose of this research project was to locate and characterize a distinct neuronal hyperexcitability defect favoring spike-wave synchronization in the stargazer brain. One experimental approach for anatomically locating areas of synchronization and hyperexcitability involved an attempt to map patterns of hypersynchronous activity with antibodies to activity-induced proteins.^ A second approach to characterizing the neuronal defect involved examining the neuronal responses in the mutant following application of pharmacological agents with well known sites of action.^ In order to test the hypothesis that an NMDA receptor mediated hyperexcitability defect exists in stargazer neocortex, extracellular field recordings were used to examine the effects of CPP and MK-801 on coronal neocortical brain slices of stargazer and wild type perfused with 0 Mg$\sp{2+}$ artificial cerebral spinal fluid (aCSF).^ To study how NMDA receptor antagonists might promote increased excitability in stargazer neocortex, two basic hypotheses were tested: (1) NMDA receptor antagonists directly activate deep layer principal pyramidal cells in the neocortex of stargazer, presumably by opening NMDA receptor channels altered by the stg mutation; and (2) NMDA receptor antagonists disinhibit the neocortical network by blocking recurrent excitatory synaptic inputs onto inhibitory interneurons in the deep layers of stargazer neocortex.^ In order to test whether CPP might disinhibit the 0 Mg$\sp{2+}$ bursting network in the mutant by acting on inhibitory interneurons, the inhibitory inputs were pharmacologically removed by application of GABA receptor antagonists to the cortical network, and the effects of CPP under 0 Mg$\sp{2+}$aCSF perfusion in layer V of stg/stg were then compared with those found in +/+ neocortex using in vitro extracellular field recordings. (Abstract shortened by UMI.) ^

Reduced order models for industrial thermo-fluid problems

A new method is presented to generate reduced order models (ROMs) in Fluid Dynamics problems of industrial interest. The method is based on the expansion of the flow variables in a Proper Orthogonal Decomposition (POD) basis, calculated from a limited number of snapshots, which are obtained via Computational Fluid Dynamics (CFD). Then, the POD-mode amplitudes are calculated as minimizers of a properly defined overall residual of the equations and boundary conditions. The method includes various ingredients that are new in this field. The residual can be calculated using only a limited number of points in the flow field, which can be scattered either all over the whole computational domain or over a smaller projection window. The resulting ROM is both computationally efficient(reconstructed flow fields require, in cases that do not present shock waves, less than 1 % of the time needed to compute a full CFD solution) and flexible(the projection window can avoid regions of large localized CFD errors).Also, for problems related with aerodynamics, POD modes are obtained from a set of snapshots calculated by a CFD method based on the compressible Navier Stokes equations and a turbulence model (which further more includes some unphysical stabilizing terms that are included for purely numerical reasons), but projection onto the POD manifold is made using the inviscid Euler equations, which makes the method independent of the CFD scheme. In addition, shock waves are treated specifically in the POD description, to avoid the need of using a too large number of snapshots. Various definitions of the residual are also discussed, along with the number and distribution of snapshots, the number of retained modes, and the effect of CFD errors. The method is checked and discussed on several test problems that describe (i) heat transfer in the recirculation region downstream of a backwards facing step, (ii) the flow past a two-dimensional airfoil in both the subsonic and transonic regimes, and (iii) the flow past a three-dimensional horizontal tail plane. The method is both efficient and numerically robust in the sense that the computational effort is quite small compared to CFD and results are both reasonably accurate and largely insensitive to the definition of the residual, to CFD errors, and to the CFD method itself, which may contain artificial stabilizing terms. Thus, the method is amenable for practical engineering applications. Resumen Se presenta un nuevo método para generar modelos de orden reducido (ROMs) aplicado a problemas fluidodinámicos de interés industrial. El nuevo método se basa en la expansión de las variables fluidas en una base POD, calculada a partir de un cierto número de snapshots, los cuales se han obtenido gracias a simulaciones numéricas (CFD). A continuación, las amplitudes de los modos POD se calculan minimizando un residual global adecuadamente definido que combina las ecuaciones y las condiciones de contorno. El método incluye varios ingredientes que son nuevos en este campo de estudio. El residual puede calcularse utilizando únicamente un número limitado de puntos del campo fluido. Estos puntos puede encontrarse dispersos a lo largo del dominio computacional completo o sobre una ventana de proyección. El modelo ROM obtenido es tanto computacionalmente eficiente (en aquellos casos que no presentan ondas de choque reconstruir los campos fluidos requiere menos del 1% del tiempo necesario para calcular una solución CFD) como flexible (la ventana de proyección puede escogerse de forma que evite contener regiones con errores en la solución CFD localizados y grandes). Además, en problemas aerodinámicos, los modos POD se obtienen de un conjunto de snapshots calculados utilizando un código CFD basado en la versión compresible de las ecuaciones de Navier Stokes y un modelo de turbulencia (el cual puede incluir algunos términos estabilizadores sin sentido físico que se añaden por razones puramente numéricas), aunque la proyección en la variedad POD se hace utilizando las ecuaciones de Euler, lo que hace al método independiente del esquema utilizado en el código CFD. Además, las ondas de choque se tratan específicamente en la descripción POD para evitar la necesidad de utilizar un número demasiado grande de snapshots. Varias definiciones del residual se discuten, así como el número y distribución de los snapshots,el número de modos retenidos y el efecto de los errores debidos al CFD. El método se comprueba y discute para varios problemas de evaluación que describen (i) la transferencia de calor en la región de recirculación aguas abajo de un escalón, (ii) el flujo alrededor de un perfil bidimensional en regímenes subsónico y transónico y (iii) el flujo alrededor de un estabilizador horizontal tridimensional. El método es tanto eficiente como numéricamente robusto en el sentido de que el esfuerzo computacional es muy pequeño comparado con el requerido por el CFD y los resultados son razonablemente precisos y muy insensibles a la definición del residual, los errores debidos al CFD y al método CFD en sí mismo, el cual puede contener términos estabilizadores artificiales. Por lo tanto, el método puede utilizarse en aplicaciones prácticas de ingeniería.

Ferromanganese nodules and micro-hardgrounds associated with the Cadiz Contourite Channel (NE Atlantic): Palaeoenvironmental records of fluid venting and bottom currents

Ferromanganese nodule fields and hardgrounds have recently been discovered in the Cadiz Contourite Channel in the Gulf of Cadiz (850–1000 m). This channel is part of a large contourite depositional system generated by the Mediterranean Outflow Water. Ferromanganese deposits linked to contourites are interesting tools for palaeoenviromental studies and show an increasing economic interest as potential mineral resources for base and strategic metals. We present a complete characterisation of these deposits based on submarine photographs and geophysical, petrographic, mineralogical and geochemical data. The genesis and growth of ferromanganese deposits, strongly enriched in Fe vs. Mn (av. 39% vs. 6%) in this contourite depositional system result from the combination of hydrogenetic and diagenetic processes. The interaction of the Mediterranean Outflow Water with the continental margin has led to the formation of Late Pleistocene–Holocene ferromanganese mineral deposits, in parallel to the evolution of the contourite depositional system triggered by climatic and tectonic events. The diagenetic growth was fuelled by the anaerobic oxidation of thermogenic hydrocarbons (δ13CPDB=−20 to −37‰) and organic matter within the channel floor sediments, promoting the formation of Fe–Mn carbonate nodules. High 87Sr/86Sr isotopic values (up to 0.70993±0.00025) observed in the inner parts of nodules are related to the influence of radiogenic fluids fuelled by deep-seated fluid venting across the fault systems in the diapirs below the Cadiz Contourite Channel. Erosive action of the Mediterranean Outflow Water undercurrent could have exhumed the Fe–Mn carbonate nodules, especially in the glacial periods, when the lower core of the undercurrent was more active in the study area. The growth rate determined by 230Thexcess/232Th was 113±11 mm/Ma, supporting the hypothesis that the growth of the nodules records palaeoenvironmental changes during the last 70 ka. Ca-rich layers in the nodules could point to the interaction between the Mediterranean Outflow Water and the North Atlantic Deep Water during the Heinrich events. Siderite–rhodochrosite nodules exposed to the oxidising seabottom waters were replaced by Fe–Mn oxyhydroxides. Slow hydrogenetic growth of goethite from the seawaters is observed in the outermost parts of the exhumed nodules and hardgrounds, which show imprints of the Mediterranean Outflow Water with low 87Sr/86Sr isotopic values (down to 0.70693±0.00081). We propose a new genetic and evolutionary model for ferromanganese oxide nodules derived from ferromanganese carbonate nodules formed on continental margins above the carbonate compensation depth and dominated by hydrocarbon seepage structures and strong erosive action of bottom currents. We also compare and discuss the generation of ferromanganese deposits in the Cadiz Contourite Channel with that in other locations and suggest that our model can be applied to ferromanganiferous deposits in other contouritic systems affected by fluid venting.

Comparison of turbulence models for the computational fluid dynamics simulation of wind turbine wakes in the atmospheric boundary layer

An elliptic computational fluid dynamics wake model based on the actuator disk concept is used to simulate a wind turbine, approximated by a disk upon which a distribution of forces, defined as axial momentum sources, is applied on an incoming non-uniform shear flow. The rotor is supposed to be uniformly loaded with the exerted forces estimated as a function of the incident wind speed, thrust coefficient and rotor diameter. The model is assessed in terms of wind speed deficit and added turbulence intensity for different turbulence models and is validated from experimental measurements of the Sexbierum wind turbine experiment.

Hexagonal patterns in a model for rotating convection

We study a model equation that mimics convection under rotation in a fluid with temperature- dependent properties (non-Boussinesq (NB)), high Prandtl number and idealized boundary conditions. It is based on a model equation proposed by Segel [1965] by adding rotation terms that lead to a Kuppers-Lortz instability [Kuppers & Lortz, 1969] and can develop into oscillating hexagons. We perform a weakly nonlinear analysis to find out explicitly the coefficients in the amplitude equation as functions of the rotation rate. These equations describe hexagons and os- cillating hexagons quite well, and include the Busse?Heikes (BH) model [Busse & Heikes, 1980] as a particular case. The sideband instabilities as well as short wavelength instabilities of such hexagonal patterns are discussed and the threshold for oscillating hexagons is determined.

Development of a wake model for wind farms based on an open source CFD solver. Strategies on parabolization and turbulence modeling

Wake effect represents one of the most important aspects to be analyzed at the engineering phase of every wind farm since it supposes an important power deficit and an increase of turbulence levels with the consequent decrease of the lifetime. It depends on the wind farm design, wind turbine type and the atmospheric conditions prevailing at the site. Traditionally industry has used analytical models, quick and robust, which allow carry out at the preliminary stages wind farm engineering in a flexible way. However, new models based on Computational Fluid Dynamics (CFD) are needed. These models must increase the accuracy of the output variables avoiding at the same time an increase in the computational time. Among them, the elliptic models based on the actuator disk technique have reached an extended use during the last years. These models present three important problems in case of being used by default for the solution of large wind farms: the estimation of the reference wind speed upstream of each rotor disk, turbulence modeling and computational time. In order to minimize the consequence of these problems, this PhD Thesis proposes solutions implemented under the open source CFD solver OpenFOAM and adapted for each type of site: a correction on the reference wind speed for the general elliptic models, the semi-parabollic model for large offshore wind farms and the hybrid model for wind farms in complex terrain. All the models are validated in terms of power ratios by means of experimental data derived from real operating wind farms.

Transport and mixing enhancement in fluid-thermal microsystems

En esta tesis se investiga de forma experimental el transporte pasivo de magnitudes físicas en micro-sistemas con carácter de inmediata aplicación industrial, usando métodos innovadores para mejorar la eficiencia de los mismos optimizando parámetros críticos del diseño o encontrar nuevos destinos de posible aplicación. Parte de los resultados obtenidos en estos experimentos han sido publicados en revistas con un índice de impacto tal que pertenecen al primer cuarto del JCR. Primero de todo se ha analizado el efecto que produce en un intercambiador de calor basado en micro-canales el hecho de dejar un espacio entre canales y tapa superior para la interconexión de los mismos. Esto genera efectos tridimensionales que mejoran la exracción de calor del intercambiador y reducen la caída de presión que aparece por el transcurso del fluido a través de los micro-canales, lo que tiene un gran impacto en la potencia que ha de suministrar la bomba de refrigerante. Se ha analizado también la mejora producida en términos de calor disipado de un micro-procesador refrigerado con un ampliamente usado plato de aletas al implementar en éste una cámara de vapor que almacena un fluido bifásico. Se ha desarrollado de forma paralela un modelo numérico para optimizar las nuevas dimensiones del plato de aletas modificado compatibles con una serie de requerimientos de diseño en el que tanto las dimensiones como el peso juegan un papel esencial. Por otro lado, se han estudiado los fenomenos fluido-dinámicos que aparecen aguas abajo de un cuerpo romo en el seno de un fluido fluyendo por un canal con una alta relación de bloqueo. Los resultados de este estudio confirman, de forma experimental, la existencia de un régimen intermedio, caracterizado por el desarrollo de una burbuja de recirculación oscilante entre los regímenes, bien diferenciados, de burbuja de recirculación estacionaria y calle de torbellinos de Karman, como función del número de Reynolds del flujo incidente. Para la obtención, análisis y post-proceso de los datos, se ha contado con la ayuda de un sistema de Velocimetría por Imágenes de Partículas (PIV). Finalmente y como adición a este último punto, se ha estudiado las vibraciones de un cuerpo romo producidas por el desprendimiento de torbellinos en un canal de alta relación de bloqueo con la base obtenida del estudio anterior. El prisma se mueve con un movimiento armónico simple para un intervalo de números de Reynolds y este movimiento se transforma en vibración alrededor de su eje a partir de un ciero número de Reynolds. En relación al fluido, el régimen de desprendimiento de torbellinos se alcanza a menores números de Reynolds que en el caso de tener el cuerpo romo fijo. Uniendo estos dos registros de movimientos y variando la relación de masas entre prisma y fluido se obtiene un mapa con diferentes estados globales del sistema. Esto no solo tiene aplicación como método para promover el mezclado sino también como método para obtener energía a partir del movimiento del cuerpo en el seno del fluido. Abstract In this thesis, experimental research focused on passive scalar transport is performed in micro-systems with marked sense of industrial application, using innovative methods in order to obtain better performances optimizing critical design parameters or finding new utilities. Part of the results obtained in these experiments have been published into high impact factor journals belonged to the first quarter of the Journal Citation Reports (JCR). First of all the effect of tip clearance in a micro-channel based heat sink is analyzed. Leaving a gap between channels and top cover, letting the channels communicate each other causes three-dimensional effects which improve the heat transfer between fluid and heat sink and also reducing the pressure drop caused by the fluid passing through the micro-channels which has a great impact on the total cooling pumping power needed. It is also analyzed the enhancement produced in terms of dissipated heat in a micro-processor cooling system by improving the predominantly used fin plate with a vapour chamber based heat spreader which contains a two-phase fluid inside. It has also been developed at the same time a numerical model to optimize the new fin plate dimensions compatible with a series of design requirements in which both size and wight plays a very restrictive role. On the other hand, fluid-dynamics phenomena that appears downstream of a bluff body in the bosom of a fluid flow with high blockage ratio has been studied. This research experimentally confirms the existence of an intermediate regime characterized by an oscillating closed recirculation bubble intermediate regime between the steady closed recirculation bubble regime and the vortex shedding regime (Karman street like regime) as a function of the incoming flow Reynolds number. A particle image velocimetry technique (PIV) has been used in order to obtain, analyze and post-process the fluid-dynamic data. Finally and as an addition to the last point, a study on the vortexinduced vibrations (VIV) of a bluff body inside a high blockage ratio channel has been carried out taking advantage of the results obtained with the fixed square prism. The prism moves with simple harmonic motion for a Reynolds number interval and this movement becomes vibrational around its axial axis after overcoming at definite Reynolds number. Regarding the fluid, vortex shedding regime is reached at Reynolds numbers lower than the previous critical ones. Merging both movement spectra and varying the square prism to fluid mass ratio, a map with different global states is reached. This is not only applicable as a mixing enhancement technique but as an energy harvesting method.

Spatial linear global instability analysis of the HIFiRE-5 elliptic cone model flow

The linear instability of the three-dimensional boundary-layer over the HIFiRE-5 flight test geometry, i.e. a rounded-tip 2:1 elliptic cone, at Mach 7, has been analyzed through spatial BiGlobal analysis, in a effort to understand transition and accurately predict local heat loads on next-generation ight vehicles. The results at an intermediate axial section of the cone, Re x = 8x10 5, show three different families of spatially amplied linear global modes, the attachment-line and cross- ow modes known from earlier analyses, and a new global mode, peaking in the vicinity of the minor axis of the cone, termed \center-line mode". We discover that a sequence of symmetric and anti-symmetric centerline modes exist and, for the basic ow at hand, are maximally amplied around F* = 130kHz. The wavenumbers and spatial distribution of amplitude functions of the centerline modes are documented

Dynamics of gas bubbles encapsulated by a viscoelastic fluid shell under acoustic fields

The dynamics of a gas-filled microbubble encapsulated by a viscoelastic fluid shell immersed in a Newtonian liquid and subject to an external pressure field is theoretically studied. The problem is formulated by considering a nonlinear Oldroyd type constitutive equation to model the rheological behavior of the fluid shell. Heat and mass transfer across the surface bubble have been neglected but radiation losses due to the compressibility of the surrounding liquid have been taken into account. Bubble collapse under sudden increase of the external pressure as well as nonlinear radial oscillations under ultrasound fields are investigated. The numerical results obtained show that the elasticity of the fluid coating intensifies oscillatory collapse and produces a strong increase of the amplitudes of radial oscillations which may become chaotic even for moderate driving pressure amplitudes. The role played by the elongational viscosity has also been analyzed and its influence on both, bubble collapse and radial oscillations, has been recognized. According to the theoretical predictions provided in the present work, a microbubble coated by a viscoelastic fluid shell is an oscillating system that, under acoustic driving, may experience volume oscillations of large amplitude, being, however, more stable than a free bubble. Thus, it could be expected that such a system may have a suitable behavior as an echogenic agent.

A gradient-enhanced continuum damage model with application to fibre-reinforced tissues at finite strains

A non-local gradient-based damage formulation within a geometrically non-linear set- ting is presented. The hyperelastic constitutive response at local material point level is governed by a strain energy function which is additively composed by an isotropic neo-Hookean matrix and by an anisotropic fibre-reinforced material based on the model proposed by T. Gasser, R. Ogden, and G. Holzapfel.

Effect of the pulse trajectory on ultrasonic fluid velocity measurement

In a general situation a non-uniform velocity field gives rise to a shift of the otherwise straight acoustic pulse trajectory between the transmitter and receiver transducers of a sonic anemometer. The aim of this paper is to determine the effects of trajectory shifts on the velocity as measured by the sonic anemometer. This determination has been accomplished by developing a mathematical model of the measuring process carried out by sonic anemometers; a model which includes the non-straight trajectory effect. The problem is solved by small perturbation techniques, based on the relevant small parameter of the problem, the Mach number of the reference flow, M. As part of the solution, a general analytical expression for the deviations of the computed measured speed from the nominal speed has been obtained. The correction terms of both the transit time and of the measured speed are of M 2 order in rotational velocity field. The method has been applied to three simple, paradigmatic flows: one-directional horizontal and vertical shear flows, and mixed with a uniform horizontal flow.

Discrete linear stability and sensitivity analysis of fluid flows

Este trabajo presenta un método discreto para el cálculo de estabilidad hidrodinámica y análisis de sensibilidad a perturbaciones externas para ecuaciones diferenciales y en particular para las ecuaciones de Navier-Stokes compressible. Se utiliza una aproximación con variable compleja para obtener una precisión analítica en la evaluación de la matriz Jacobiana. Además, mapas de sensibilidad para la sensibilidad a las modificaciones del flujo de base y a una fuerza constante permiten identificar las regiones del campo fluido donde una modificacin (ej. fuerza puntual) tiene un efecto estabilizador del flujo. Se presentan cuatro casos de prueba: (1) un caso analítico para comprobar la derivación discreta, (2) una cavidad cerrada a bajo Reynolds para mostrar la mayor precisión en el cálculo de los valores propios con la aproximación de paso complejo, (3) flujo 2D en un cilindro circular para validar la metodología, y (4) flujo en un cavidad abierta, presentado para validar el método en casos de inestabilidades convectivamente inestables. Los tres últimos casos mencionados (2-4) se resolvieron con las ecuaciones de Navier-Stokes compresibles, utilizando un método Discontinuous Galerkin Spectral Element Method. Se obtuvo una buena concordancia para el caso de validación (3), cuando se comparó el nuevo método con resultados de la literatura. Además, este trabajo muestra que para el cálculo de los modos propios directos y adjuntos, así como para los mapas de sensibilidad, el uso de variables complejas es de suprema importancia para obtener una predicción precisa. El método descrito es aplicado al análisis para la estabilización de la estela generada por un disco actuador, que representa un modelo sencillo para hélices, rotores de helicópteros o turbinas eólicas. Se explora la primera bifurcación del flujo para un disco actuador, y se sugiere que está asociada a una inestabilidad de tipo Kelvin-Helmholtz, cuya estabilidad se controla con en el número de Reynolds y en la resistencia del disco actuador (o fuerza resistente). En primer lugar, se verifica que la disminución de la resistencia del disco tiene un efecto estabilizador parecido a una disminución del Reynolds. En segundo lugar, el análisis hidrodinmico discreto identifica dos regiones para la colocación de una fuerza puntual que controle las inestabilidades, una cerca del disco y otra en una zona aguas abajo. En tercer lugar, se muestra que la inclusión de un forzamiento localizado cerca del actuador produce una estabilización más eficiente que al forzar aguas abajo. El análisis de los campos de flujo controlados confirma que modificando el gradiente de velocidad cerca del actuador es más eficiente para estabilizar la estela. Estos resultados podrían proporcionar nuevas directrices para la estabilización de la estela de turbinas de viento o de marea cuando estén instaladas en un parque eólico y minimizar las interacciones no estacionarias entre turbinas. ABSTRACT A discrete framework for computing the global stability and sensitivity analysis to external perturbations for any set of partial differential equations is presented. In particular, a complex-step approximation is used to achieve near analytical accuracy for the evaluation of the Jacobian matrix. Sensitivity maps for the sensitivity to base flow modifications and to a steady force are computed to identify regions of the flow field where an input could have a stabilising effect. Four test cases are presented: (1) an analytical test case to prove the theory of the discrete framework, (2) a lid-driven cavity at low Reynolds case to show the improved accuracy in the calculation of the eigenvalues when using the complex-step approximation, (3) the 2D flow past a circular cylinder at just below the critical Reynolds number is used to validate the methodology, and finally, (4) the flow past an open cavity is presented to give an example of the discrete method applied to a convectively unstable case. The latter three (2–4) of the aforementioned cases were solved with the 2D compressible Navier–Stokes equations using a Discontinuous Galerkin Spectral Element Method. Good agreement was obtained for the validation test case, (3), with appropriate results in the literature. Furthermore, it is shown that for the calculation of the direct and adjoint eigenmodes and their sensitivity maps to external perturbations, the use of complex variables is paramount for obtaining an accurate prediction. An analysis for stabilising the wake past an actuator disc, which represents a simple model for propellers, helicopter rotors or wind turbines is also presented. We explore the first flow bifurcation for an actuator disc and it suggests that it is associated to a Kelvin- Helmholtz type instability whose stability relies on the Reynolds number and the flow resistance applied through the disc (or actuator forcing). First, we report that decreasing the disc resistance has a similar stabilising effect to an decrease in the Reynolds number. Second, a discrete sensitivity analysis identifies two regions for suitable placement of flow control forcing, one close to the disc and one far downstream where the instability originates. Third, we show that adding a localised forcing close to the actuator provides more stabilisation that forcing far downstream. The analysis of the controlled flow fields, confirms that modifying the velocity gradient close to the actuator is more efficient to stabilise the wake than controlling the sheared flow far downstream. An interesting application of these results is to provide guidelines for stabilising the wake of wind or tidal turbines when placed in an energy farm to minimise unsteady interactions.

Fluid-solid interaction in arteries incorporating the autoregulation concept in boundary conditions

In pre-surgery decisions in hospital emergency cases, fast and reliable results of the solid and fluid mechanics problems are of great interest to clinicians. In the current investigation, an iterative process based on a pressure-type boundary condition is proposed in order to reduce the computational costs of blood flow simulations in arteries, without losing control of the important clinical parameters. The incorporation of cardiovascular autoregulation, together with the well-known impedance boundary condition, forms the basis of the proposed methodology. With autoregulation, the instabilities associated with conventional pressure-type or impedance boundary conditions are avoided without an excessive increase in computational costs. The general behaviour of pulsatile blood flow in arteries, which is important from the clinical point of view, is well reproduced through this new methodology. In addition, the interaction between the blood and the arterial walls occurs via a modified weak coupling, which makes the simulation more stable and computationally efficient. Based on in vitro experiments, the hyperelastic behaviour of the wall is characterised and modelled. The applications and benefits of the proposed pressure-type boundary condition are shown in a model of an idealised aortic arch with and without an ascending aorta dissection, which is a common cardiovascular disorder.

The elasticity and failure of fluid-filled cellular solids: Theory and experiment

We extend and apply theories of filled foam elasticity and failure to recently available data on foods. The predictions of elastic modulus and failure mode dependence on internal pressure and on wall integrity are borne out by photographic evidence of distortion and failure under compressive loading and under the localized stress applied by a knife blade, and by mechanical data on vegetables differing only in their turgor pressure. We calculate the dry modulus of plate-like cellular solids and the cross over between dry-like and fully fluid-filled elastic response. The bulk elastic properties of limp and aging cellular solids are calculated for model systems and compared with our mechanical data, which also show two regimes of response. The mechanics of an aged, limp beam is calculated, thus offering a practical procedure for comparing experiment and theory. This investigation also thereby offers explanations of the connection between turgor pressure and crispness and limpness of cellular materials.

Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers.

A soluble form of Alzheimer disease amyloid beta-protein (sA beta) is transported in the blood and cerebrospinal fluid mainly complexed with apolipoprotein J (apoJ). Using a well-characterized in situ perfused guinea pig brain model, we recently obtained preliminary evidence that apoJ facilitates transport of sA beta (1-40)-apoJ complexes across the blood-brain barrier and the blood-cerebrospinal fluid barrier, but the mechanisms remain poorly understood. In the present study, we examined the transport process in greater detail and investigated the possible role of glycoprotein 330 (gp330)/megalin, a receptor for multiple ligands, including apoJ. High-affinity transport systems with a Km of 0.2 and 0.5 nM were demonstrated for apoJ at the blood-brain barrier and the choroid epithelium in vivo, suggesting a specific receptor-mediated mechanism. The sA beta (1-40)-apoJ complex shared the same transport mechanism and exhibited 2.4- to 10.2-fold higher affinity than apoJ itself. Binding to microvessels, transport into brain parenchyma, and choroidal uptake of both apoJ and sA beta (1-40)-apoJ complexes were markedly inhibited (74-99%) in the presence of a monoclonal antibody to gp330/megalin and were virtually abolished by perfusion with the receptor-associated protein, which blocks binding of all known ligands to gp330. Western blot analysis of cerebral microvessels with the monoclonal antibody to gp330 revealed a protein with a mass identical to that in extracts of kidney membranes enriched with gp330/megalin, but in much lower concentration. The findings suggest that gp330/megalin mediates cellular uptake and transport of apoJ and sA beta (1-40)-apoJ complex at the cerebral vascular endothelium and choroid epithelium.