A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles.

Representing spray zone with cross flow as a well-mixed compartment in a high shear granulator

The spray zone is an important region to control nucleation of granules in a high shear granulator. In this study, a spray zone with cross flow is quantified as a well-mixed compartment in a high shear granulator. Granulation kinetics is quantitatively derived at both particle-scale and spray zone-scale. Two spatial decay rates, DGSDR (droplet-granule spatial decay rate) ζDG and DPSDR (droplet-primary particle spatial decay rate) ζDP, which are functions of volume fraction and diameter of particulate species within the powder bed, are defined to simplify the deduction. It is concluded that in cross flow, explicit analytical results show that the droplet concentration is subject to exponential decay with depth which produces a numerically infinite depth of spray zone in a real penetration process. In a well-mixed spray zone, the depth of the spray zone is 4/(ζDG + ζDP) and π2/3(ζDG + ζDP) in cuboid and cylinder shape, respectively. The first-order droplet-based collision rates of, nucleation rate B0 and rewetting rate RW0 are uncorrelated with the flow pattern and shape of the spray zone. The second-order droplet-based collision rate, nucleated granule-granule collision rate RGG, is correlated with the mixing pattern. Finally, a real formulation case of a high shear granulation process is used to estimate the size of the spray zone. The results show that the spray zone is a thin layer at the powder bed surface. We present, for the first time, the spray zone as a well-mixed compartment. The granulation kinetics of a well-mixed spray zone could be integrated into a Population Balance Model (PBM), particularly to aid development of a distributed model for product quality prediction.

Energy conversion assessment of vacuum, slow and fast pyrolysis processes for low and high ash paper waste sludge

The performance of vacuum, slow and fast pyrolysis processes to transfer energy from the paper waste sludge (PWS) to liquid and solid products was compared. Paper waste sludges with low and high ash content (8.5 and 46.7 wt.%) were converted under optimised conditions for temperature and pellet size to maximise both product yields and energy content. Comparison of the gross energy conversions, as a combination of the bio-oil/tarry phase and char (ECsum), revealed that the fast pyrolysis performance was between 18.5% and 20.1% higher for the low ash PWS, and 18.4% and 36.5% higher for high ash PWS, when compared to the slow and vacuum pyrolysis processes respectively. For both PWSs, this finding was mainly attributed to higher production of condensable organic compounds and lower water yields during FP. The low ash PWS chars, fast pyrolysis bio-oils and vacuum pyrolysis tarry phase products had high calorific values (∼18-23 MJ kg-1) making them promising for energy applications. Considering the low calorific values of the chars from alternative pyrolysis processes (∼4-7 MJ kg-1), the high ash PWS should rather be converted to fast pyrolysis bio-oil to maximise the recovery of usable energy products.

Low- vs. high-glycemic load diets: effects on postprandial plasma free fatty acids

Thesis (Master's)--University of Washington, 2016-06

Effect of galactose metabolising and non-metabolising strains of Streptococcus thermophilus as a starter culture adjunct on the properties of Cheddar cheese made with low or high pH at whey drainage

Cheddar cheese was made using control culture (Lactococcus lactis subsp. lactis), or with control culture plus a galactose-metabolising (Gal+) or galactose-non-metabolising (Gal-) Streptococcus thermophilus adjunct; for each culture type, the pH at whey drainage was either low (pH 6.15) or high (pH 6.45). Sc. thermophilus affected the levels of residual lactose and galactose, and the volatile compound profile and sensory properties of the mature cheese (270 d) to an extent dependent on the drain pH and phenotype (Gal+ or Gal-). For all culture systems, reducing drain pH resulted in lower levels of moisture and lactic acid, a higher concentration of free amino acids, and higher firmness. The results indicate that Sc. thermophilus may be used to diversify the sensory properties of Cheddar cheese, for example from a fruity buttery odour and creamy flavour to a more acid taste, rancid odour, and a sweaty cheese flavour at high drain pH.

Material characterization and process development for indium-arsenide / indium-gallium-antimonide channel, high electron mobility transistors for low power, high speed applications

Efforts to push the performance of transistors for millimeter-wave and microwave applications have borne fruit through device size scaling and the use of novel material systems. III-V semiconductors and their alloys hold a distinct advantage over silicon because they have much higher electron mobility which is a prerequisite for high frequency operation. InGaAs/InP pseudomorphic heterojunction bipolar transistors (HBTs) have demonstrated fT of 765 GHz at room temperature and InP based high electron mobility transistors (HEMTs) have demonstrated fMax of 1.2 THz. The 6.1 A lattice family of InAs, GaSb, AlSb covers a wide variety of band gaps and is an attractive future material system for high speed device development. Extremely high electron mobilities ~ 30,000 cm^2 V^-1s^-1 have been achieved in modulation doped InAs-AlSb structures. The work described in this thesis involves material characterization and process development for HEMT fabrication on this material system.

Low-power high-performance SAR ADC design with digital calibration techniques

This dissertation presents the design of three high-performance successive-approximation-register (SAR) analog-to-digital converters (ADCs) using distinct digital background calibration techniques under the framework of a generalized code-domain linear equalizer. These digital calibration techniques effectively and efficiently remove the static mismatch errors in the analog-to-digital (A/D) conversion. They enable aggressive scaling of the capacitive digital-to-analog converter (DAC), which also serves as sampling capacitor, to the kT/C limit. As a result, outstanding conversion linearity, high signal-to-noise ratio (SNR), high conversion speed, robustness, superb energy efficiency, and minimal chip-area are accomplished simultaneously. The first design is a 12-bit 22.5/45-MS/s SAR ADC in 0.13-μm CMOS process. It employs a perturbation-based calibration based on the superposition property of linear systems to digitally correct the capacitor mismatch error in the weighted DAC. With 3.0-mW power dissipation at a 1.2-V power supply and a 22.5-MS/s sample rate, it achieves a 71.1-dB signal-to-noise-plus-distortion ratio (SNDR), and a 94.6-dB spurious free dynamic range (SFDR). At Nyquist frequency, the conversion figure of merit (FoM) is 50.8 fJ/conversion step, the best FoM up to date (2010) for 12-bit ADCs. The SAR ADC core occupies 0.06 mm2, while the estimated area the calibration circuits is 0.03 mm2. The second proposed digital calibration technique is a bit-wise-correlation-based digital calibration. It utilizes the statistical independence of an injected pseudo-random signal and the input signal to correct the DAC mismatch in SAR ADCs. This idea is experimentally verified in a 12-bit 37-MS/s SAR ADC fabricated in 65-nm CMOS implemented by Pingli Huang. This prototype chip achieves a 70.23-dB peak SNDR and an 81.02-dB peak SFDR, while occupying 0.12-mm2 silicon area and dissipating 9.14 mW from a 1.2-V supply with the synthesized digital calibration circuits included. The third work is an 8-bit, 600-MS/s, 10-way time-interleaved SAR ADC array fabricated in 0.13-μm CMOS process. This work employs an adaptive digital equalization approach to calibrate both intra-channel nonlinearities and inter-channel mismatch errors. The prototype chip achieves 47.4-dB SNDR, 63.6-dB SFDR, less than 0.30-LSB differential nonlinearity (DNL), and less than 0.23-LSB integral nonlinearity (INL). The ADC array occupies an active area of 1.35 mm2 and dissipates 30.3 mW, including synthesized digital calibration circuits and an on-chip dual-loop delay-locked loop (DLL) for clock generation and synchronization.

Heat transfer rates for cross flow of water through a tube bank at high Reynolds numbers.

Mode of access: Internet.

Efficiency of low versus high airline pressure on stunning cattle with penetrating captive bolt guns.

2016

Experimental analysis of coaxial jets: instability, flow and mixing characterization

The velocity and mixing field of two turbulent jets configurations have been experimentally characterized by means of cold- and hot-wire anemometry in order to investigate the effects of the initial conditions on the flow development. In particular, experiments have been focused on the effect of the separation wall between the two streams on the flow field. The results of the experiments have pointed out that the wake behind a thick wall separating wall has a strong influence on the flow field evolution. For instance, for nearly unitary velocity ratios, a clear vortex shedding from the wall is observable. This phenomenon enhances the mixing between the inner and outer shear layer. This enhancement in the fluctuating activity is a consequence of a local absolute instability of the flow which, for a small range of velocity ratios, behaves as an hydrodynamic oscillator with no sensibility to external perturbations. It has been suggested indeed that this absolute instability can be used as a passive method to control the flow evolution. Finally, acoustic excitation has been applied to the near field in order to verify whether or not the observed vortex shedding behind the separating wall is due to a global oscillating mode as predicted by the theory. A new scaling relationship has been also proposed to determine the preferred frequency for nearly unitary velocity ratios. The proposed law takes into account both the Reynolds number and the velocity ratio dependence of this frequency and, therefore, improves all the previously proposed relationships.

Experimental studies on transitional separated boundary layers

Separated transitional boundary layers appear on key aeronautical processes such as the flow around wings or turbomachinery blades. The aim of this thesis is the study of these flows in representative scenarios of technological applications, gaining knowledge about phenomenology and physical processes that occur there and, developing a simple model for scaling them. To achieve this goal, experimental measurements have been carried out in a low speed facility, ensuring the flow homogeneity and a low disturbances level such that unwanted transitional mechanisms are avoided. The studied boundary layers have been developed on a flat plate, by imposing a pressure gradient by means of contoured walls. They generate an initial acceleration region followed by a deceleration zone. The initial region is designed to obtain at the beginning of the deceleration the Blasius profile, characterized by its momentum thickness, and an edge boundary layer velocity, defining the problem characteristic velocity. The deceleration region is designed to obtain a linear evolution of the edge velocity, thereby defining the characteristic length of the problem. Several experimental techniques, both intrusive (hot wire anemometry, total pressure probes) as nonintrusive (PIV and LDV anemometry, high-speed filming), have been used in order to take advantage of each of them and allow cross-validation of the results. Once the boundary layer at the deceleration beginning has been characterized, ensuring the desired integral parameters and level of disturbance, the evolution of the laminar boundary layer up to the point of separation is studied. It has been compared with integral methods, and numerical simulations. In view of the results a new model for this evolution is proposed. Downstream from the separation, the flow near to the wall is configured as a shear layer that encloses low momentum recirculating fluid. The region where the shear layer remains laminar tends to be positioned to compensate the adverse pressure gradient associated with the imposed deceleration. Under these conditions, the momentum thickness remains almost constant. This laminar shear layer region extends up to where transitional phenomena appear, extension that scales with the momentum thickness at separation. These transitional phenomena are of inviscid type, similar to those found in free shear layers. The transitional region analysis begins with a study of the disturbances evolution in the linear growth region and the comparison of experimental results with a numerical model based on Linear Stability Theory for parallel flows and with data from other authors. The results’ coalescence for both the disturbances growth and the excited frequencies is stated. For the transition final stages the vorticity concentration into vortex blobs is found, analogously to what happens in free shear layers. Unlike these, the presence of the wall and the pressure gradient make the large scale structures to move towards the wall and quickly disappear under certain circumstances. In these cases, the recirculating flow is confined into a closed region saying the bubble is closed or the boundary layer reattaches. From the reattachment point, the fluid shows a configuration in the vicinity of the wall traditionally considered as turbulent. It has been observed that existing integral methods for turbulent boundary layers do not fit well to the experimental results, due to these methods being valid only for fully developed turbulent flow. Nevertheless, it has been found that downstream from the reattachment point the velocity profiles are self-similar, and a model has been proposed for the evolution of the integral parameters of the boundary layer in this region. Finally, the phenomenon known as bubble burst is analyzed. It has been checked the validity of existing models in literature and a new one is proposed. This phenomenon is blamed to the inability of the large scale structures formed after the transition to overcome with the adverse pressure gradient, move towards the wall and close the bubble. El estudio de capas límites transicionales con separación es de gran relevancia en distintas aplicaciones tecnológicas. Particularmente, en tecnología aeronáutica, aparecen en procesos claves, tales como el flujo alrededor de alas o álabes de turbomaquinaria. El objetivo de esta tesis es el estudio de estos flujos en situaciones representativas de las aplicaciones tecnológicas, ganando por un lado conocimiento sobre la fenomenología y los procesos físicos que aparecen y, por otra parte, desarrollando un modelo sencillo para el escalado de los mismos. Para conseguir este objetivo se han realizado ensayos en una instalación experimental de baja velocidad específicamente diseñada para asegurar un flujo homogéneo y con bajo nivel de perturbaciones, de modo que se evita el disparo de mecanismos transicionales no deseados. La capa límite bajo estudio se ha desarrollado sobre una placa plana, imponiendo un gradiente de presión a la misma por medio de paredes de geometría especificada. éstas generan una región inicial de aceleración seguida de una zona de deceleración. La región inicial se diseña para tener en al inicio de la deceleración un perfil de capa límite de Blasius, caracterizado por su espesor de cantidad de movimiento, y una cierta velocidad externa a la capa límite que se considera la velocidad característica del problema. La región de deceleración está concebida para que la variación de la velocidad externa a la capa límite sea lineal, definiendo de esta forma una longitud característica del problema. Los ensayos se han realizado explotando varias técnicas experimentales, tanto intrusivas (anemometría de hilo caliente, sondas de presión total) como no intrusivas (anemometrías láser y PIV, filmación de alta velocidad), de cara a aprovechar las ventajas de cada una de ellas y permitir validación cruzada de resultados entre las mismas. Caracterizada la capa límite al comienzo de la deceleración, y garantizados los parámetros integrales y niveles de perturbación deseados se procede al estudio de la zona de deceleración. Se presenta en la tesis un análisis de la evolución de la capa límite laminar desde el inicio de la misma hasta el punto de separación, comparando con métodos integrales, simulaciones numéricas, y proponiendo un nuevo modelo para esta evolución. Aguas abajo de la separación, el flujo en las proximidades de la pared se configura como una capa de cortadura que encierra una región de fluido recirculatorio de baja cantidad de movimiento. Se ha caracterizado la región en que dicha capa de cortadura permanece laminar, encontrando que se posiciona de modo que compensa el gradiente adverso de presión asociado a la deceleración de la corriente. En estas condiciones, el espesor de cantidad de movimiento permanece prácticamente constante y esta capa de cortadura laminar se extiende hasta que los fenómenos transicionales aparecen. Estos fenómenos son de tipo no viscoso, similares a los que aparecen en una capa de cortadura libre. El análisis de la región transicional comienza con un estudio de la evolución de las vii viii RESUMEN perturbaciones en la zona de crecimiento lineal de las mismas y la comparación de los resultados experimentales con un modelo numérico y con datos de otros autores. La coalescencia de los resultados tanto para el crecimiento de las perturbaciones como para las frecuencias excitadas queda demostrada. Para los estadios finales de la transición se observa la concentración de la vorticidad en torbellinos, de modo análogo a lo que ocurre en capas de cortadura libres. A diferencia de estas, la presencia de la pared y del gradiente de presión hace que, bajo ciertas condiciones, la gran escala se desplace hacia la pared y desaparezca rápidamente. En este caso el flujo recirculatorio queda confinado en una región cerrada y se habla de cierre de la burbuja o readherencia de la capa límite. A partir del punto de readherencia se tiene una configuración fluida en las proximidades de la pared que tradicionalmente se ha considerado turbulenta. Se ha observado que los métodos integrales existentes para capas límites turbulentas no ajustan bien a las medidas experimentales realizadas, hecho imputable a que no se obtiene en dicha región un flujo turbulento plenamente desarrollado. Se ha encontrado, sin embargo, que pasado el punto de readherencia los perfiles de velocidad próximos a la pared son autosemejantes entre sí y se ha propuesto un modelo para la evolución de los parámetros integrales de la capa límite en esta región. Finalmente, el fenómeno conocido como “estallido” de la burbuja se ha analizado. Se ha comprobado la validez de los modelos existentes en la literatura y se propone uno nuevo. Este fenómeno se achaca a la incapacidad de la gran estructura formada tras la transición para vencer el gradiente adverso de presión, desplazarse hacia la pared y cerrar la burbuja.

Temperature measurements in turbulent pipe flow with cold wire anemometry

Passive scalars measurements in turbulent pipe flows are difficult to perform and only few experimental data are available in literature. The present thesis deals with the experimental acquisition and study of the first turbulent temperature profile inside the CICLoPE wind tunnel through cold wire anemometry technique at Reτ = 6000 and Reτ = 9500. This type of measurements provides not only useful data on temperature (and passive scalars) behaviour and statistics in turbulent pipe flows, but could be used also for temperature correction of turbulent velocity profiles. In the present work, subsequent acquisitions of temperature and velocity profiles has been performed at the same Reynolds number and in the same points, through cold wire and hot wire techniques respectively. Taking as reference data from both DNS and experimental campaigns, the activity has been carried out obtaining satisfactory results. We have verified the presence of turbulent temperature profile inside the CICLoPE wind tunnel and then studied its statistical and spectral behaviours obtaining results in agreement with existing data from Hishida, Nagano, and Ferro. Cold wire temperature data were then used to correct hot wire velocity data, obtaining a slightly improvement in the near wall region.

Experimental study of a Tollmien-Schlichting wave interacting with a shallow 3D roughness element

The paper is devoted to an experimental study of the effect of a shallow 3D roughness element on the evolution of a 2D Tollmien-Schlichting wave in a Blasius boundary layer. The experiments were carried out under controlled disturbance conditions on an airfoil section which could provide a long run with zero pressure gradient flow. A pneumatically driven slit source was used to introduce the Tollmien-Schilichting wave upstream of the lower branch of the neutral stability curve. A few wavelengths downstream, the T-S wave interacts with a cylindrical roughness element. The height of the roughness was slowly oscillating in time, which allows a continuous measurement of the T-S wave response downstream the roughness. The oscillation frequency was approximately 1500 times lower than the frequency of the studied Tollmien-Schlichting wave and therefore, behaved as a steady roughness with respect to the T-S wave. Hot wire anemometry was used to measure wall normal profiles and spanwise scans close to the maximum of the eigenfunction of the T-S wave. The oscillation of the roughness and the synchronization of all-equipments permitted the use of ensemble average techniques. Two different amplitudes of T-S waves with a non-dimensional frequency of F120E-06 were studied. They show a strong amplification of the disturbances in a small spanwise wave number range. The analysis of the wall normal T-S profiles suggests the growth of oblique modes.

Analyse selbsterregter Strömungsfelder im Verdichter-Leitrad durch Kopplung von Particle Image Velocimetry und Hitzdrahtanemometrie mittels Fast Fourier Transformation

Der Einsatz der Particle Image Velocimetry (PIV) zur Analyse selbsterregter Strömungsphänomene und das dafür notwendige Auswerteverfahren werden in dieser Arbeit beschrieben. Zur Untersuchung von solchen Mechanismen, die in Turbo-Verdichtern als Rotierende Instabilitäten in Erscheinung treten, wird auf Datensätze zurückgegriffen, die anhand experimenteller Untersuchungen an einem ringförmigen Verdichter-Leitrad gewonnen wurden. Die Rotierenden Instabilitäten sind zeitabhängige Strömungsphänomene, die bei hohen aerodynamischen Belastungen in Verdichtergittern auftreten können. Aufgrund der fehlenden Phaseninformation kann diese instationäre Strömung mit konventionellen PIV-Systemen nicht erfasst werden. Die Kármánsche Wirbelstraße und Rotierende Instabilitäten stellen beide selbsterregte Strömungsvorgänge dar. Die Ähnlichkeit wird genutzt um die Funktionalität des Verfahrens anhand der Kármánschen Wirbelstraße nachzuweisen. Der mittels PIV zu visualisierende Wirbeltransport erfordert ein besonderes Verfahren, da ein externes Signal zur Festlegung des Phasenwinkels dieser selbsterregten Strömung nicht zur Verfügung steht. Die Methodik basiert auf der Kopplung der PIV-Technik mit der Hitzdrahtanemometrie. Die gleichzeitige Messung mittels einer zeitlich hochaufgelösten Hitzdraht-Messung ermöglicht den Zeitpunkten der PIV-Bilder einen Phasenwinkel zuzuordnen. Hierzu wird das Hitzdrahtsignal mit einem FFT-Verfahren analysiert, um die PIV-Bilder entsprechend ihrer Phasenwinkel zu gruppieren. Dafür werden die aufgenommenen Bilder auf der Zeitachse der Hitzdrahtmessungen markiert. Eine systematische Analyse des Hitzdrahtsignals in der Umgebung der PIV-Messung liefert Daten zur Festlegung der Grundfrequenz und erlaubt es, der markierten PIV-Position einen Phasenwinkel zuzuordnen. Die sich aus den PIV-Bildern einer Klasse ergebenden Geschwindigkeitskomponenten werden anschließend gemittelt. Aus den resultierenden Bildern jeder Klasse ergibt sich das zweidimensionale zeitabhängige Geschwindigkeitsfeld, in dem die Wirbelwanderung der Kármánschen Wirbelstraße ersichtlich wird. In hierauf aufbauenden Untersuchungen werden Zeitsignale aus Messungen in einem Verdichterringgitter analysiert. Dabei zeigt sich, dass zusätzlich Filterfunktionen erforderlich sind. Im Ergebnis wird schließlich deutlich, dass die Übertragung der anhand der Kármánschen Wirbelstraße entwickelten Methode nur teilweise gelingt und weitere Forschungsarbeiten erforderlich sind.