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The Gorda Basin is a young oceanic plate which comes in direct contact with the convergent margin of western North America. Two long sonobuoy refraction profiles crossing the basin provide nearly continuous data for computing the velocity structure of the crust and adjacent continental slope. Time-term analysis utilizing multiple receivers and overlapping profiles revealed a thick transition layer which averages 2.3 km but displays considerable lateral variation. The seismic compressional velocity of this layer is 5.3 km/sec. Th average thickness of Layer 3 is 3.4 km with a velocity of 6.9 km/sec. The base of the crust is marked by the seismic Moho, the velocity below which is 8.1 km/sec. Refraction and reflection studies of sediment cover indicate a thickening of turbidite deposits to the southeast from less than 100 meters to over 2.5 km along the continental margin. Ophiolite studies indicate that the top of Layer 3 marks the upper extent of amphibolite facies metamorphism of basaltic sheeted dikes. Lateral depth variations of this seismic boundary in the Gorda Basin may suggest the occurrence of isograd relief along the spreading center. The Moho marks the boundary between mafic and ultramafic rocks near the ridge but may represent the maximum depth of serpentinization in the crust after it moves away from the spreading axis. Thin crust (4-5 km) and deep bathymetry in the central portion of the basin have resulted from crustal formation processes occurring at ridge crest offsets and are coincident with recent seismicity in the area. The Gorda ridge offsets and asymmetrical fan spreading of magnetic anomalies are features observed in response to a regional change in spreading directions and encroachment of the Pacific and North American plates. The Gorda plate as a whole does not respond rigidly to the resulting north-south compression. Complex structures of the continental slope, revealed by seismic reflection, limited the reduction of refraction data using plane layer methods. A simplified seismic section was computed consisting of three probable sediment layers with velocities of 1.8, 2.5 and 4.0 km/sec overlying oceanic crust. The crust is observed to dip about two degrees towards the continent at the base of the slope. A model of subduction unique to the northern California margin is one whereby young crust is subducted slowly and quickly reheated so that no brittle portion remains at normal Benioff depths. Rapid sedimentation rates balance the subduction of the crust at the margin, preventing the formation of a deep trench. / Graduation date: 1981

Seismic properties (P, S velocities and Poisson's ratio) of young (0.75 m.y.) and mature (110 m.y.) oceanic crust are obtained by studying explosive refraction data collected in the Pacific Ocean using ocean bottom and downhole seismometers. A comparison of the results for the two regions indicates that the upper crustal velocities increase with age due to the cementation of cracks and fractures, the upper mantle velocities increase with age due to cooling, and the crust (mainly the lower crust) thickens with age. The Poisson's ratios obtained in this study are too small to be consistent with the presence of any serpentinization of the lower crust or upper mantle which therefore precludes upper mantle serpentinization as the cause for the thickening of the crust with age. When comparing seismic structures of young and mature oceanic crust with ophiolite models, we find close similarities between the Samail ophiolite and young oceanic crust, and between the Bay of Islands ophiolite and old oceanic crust. The 110 m.y. old crust of the northwest Pacific Basin is characterized by high velocity gradients in the upper crust, low velocity gradients in the lower crust, a smooth 1 km-thick crust-mantle transition zone and the presence of a minimum 14% anisotropy in the upper mantle compressional wave velocities. Velocities are highest in an east-west direction. The 0.75 m.y. old crust at the intersection of the East Pacific Rise and the Orozco fracture zone is characterized by a steady increase in velocity with depth. A delay time analysis shows a trend to large Layer 3 delay times in the Orozco fracture zone indicating a thicker Layer 2 and/or low Layer 2 velocities. An investigation of different model parameterizations for the tau-zeta travel time inversion using a synthetic data set indicates that the best velocity gradient solutions, based on the least deviation of the solution from the true model, are obtained from models in which the velocities of the layer bounds take on the values of the observed velocities of the refracted waves. A trade-off curve obtained from varying the number of layers in the model shows that a model with as many layers as observed data points represents a satisfactory compromise between model resolution and solution variance. / Graduation date: 1984

Cortical Spreading Depression (CSD) is characterized by a wave of neuronal and glial depolarization followed by depression of bioelectrical activity that slowly propagates through the cortex of many species, including humans. CSD is associated with brain disorders such as stroke, head trauma and migraine. Many earlier studies have provided compelling evidence that CSD is the underlying mechanism of aura in migraine; however, whether CSD can elicit headache associated with migraine is not fully understood. Cutaneous allodynia is highly prevalent in the peri-orbital area and extracephalic sites of migraine patients, suggesting that sensitization of primary afferents and central trigeminovascular neurons in these patients could be initiated by the underlying mechanism of aura.Unlike previous reports on the interaction between CSD and the trigeminal system, in which nociceptive behavior could not be measured since they employed anesthetized animals, we designed a model in which freely moving rats could be monitored for both CSD events and behavior responses due to pinprick plus KCl injection to the occipital cortex. We show that significant tactile hypersensitivity of the periorbital region of the face and hindpaws develop in a time-dependent manner following CSD. Enhanced expression of Fos protein and increased mRNA levels of the inflammatory cytokines IL-1beta and IL-6 are found within the trigeminal nucleus caudalis (TNC) two hours following cortical injection. We further show that systemic administration of anti-migraine drugs such as sumatriptan, naproxen and CGRP(8-37) (a CGRP antagonist) attenuate the generalized allodynia that ensue following cortical stimulation by KCl. Microinjection of bupivacaine in the ipsilateral trigeminal ganglion or in the rostral ventromedial medulla (RVM) prior to cortical pinprick plus KCl injection reversibly diminishes tactile hypersensitivity, suggesting that RVM pain-facilitating cells become activated by a trigeminal-RVM pathway following CSD. In addition we demonstrate that cortical pinprick plus KCl injection induced CSD events in 24/28 (85%) rats, among which 66% and 87% developed allodynia in the face and hindpaw, respectively.These studies suggest a potential association between CSD and development of hypersensitivity in rats, indicating that this model can be used to investigate the role of CSD-evoked migraine-related pain and to explore novel therapeutic strategies.

The analysis and modelling of magnetic anomalies at the conjugate rifted continental margins of the southern Iberia Abyssal Plain (TAP) and Newfoundland Basin have revealed that the sources of magnetic anomalies are distinctly different across both each margin and between the two margins. Analyses of synthetic anomalies and gridded sea surface magnetic anomaly charts west of Iberia and east of Newfoundland were accomplished by the methods of Euler deconvolution, forward and inverse modelling of the power spectrum, reduction-to-the-pole, and forward and inverse indirect methods. In addition, three near-bottom magnetometer profiles were analysed by the same methods in addition to the application of componental magnetometry. The results have revealed that oceanic crust, transitional basement and thinned continental crust are defined by magnetic sources with different characteristics. Over oceanic crust, magnetic sources are present as lava-flow-like bodies whose depths coincide with the top of acoustic basement seen on MCS profiles. Top-basement source depths are consistent with those determined in two other regions of oceanic crust. In the southern IAP, oceanic crust, ~4 km thick with magnetizations up to +1.5 A/m, generated by organized seafloor spreading was first accreted -126 Ma at the position of a N-S oriented segmented basement peridotite ridge. To the west, seafloor spreading anomalies can be modelled at spreading rates of 10 mm/yr or more. Immediately to the east, in a zone -10-20 km in width, I identify seafloor spreading anomahes which can only be modelled assuming variable spreading rates. In the OCT, sources of magnetic anomalies are present at the top of basement and up to -6 km beneath. I interpret the uppermost source as serpentinized peridotite, and the lowermost source as intruded gabbroic bodies which were impeded, whilst rising upwards, by the lower density serpentinized peridotites. Intrusion was accompanied by tectonism and a gradual change in conditions from rifting to seafloor spreading as the North Atlantic rift propagated northwards in Early Cretaceous times. Within thinned continental crust, sources are poorly lineated, and distributed in depth. Scaling relationships of susceptibility are consistent with the sources of magnetic anomalies within continental crust. OCT-type intrusions may be present in the mantle beneath continental crust. At the conjugate Newfoundland margin, seafloor spreading anomalies can be modelled at rates of 8 and 10 mm/yr suggesting an onset age consistent with that of the IAP. In the OCT there, I propose that magnetic anomalies are sourced in near top-basement serpentinized peridotites. An absence of magmatic material and the differences in basement character (with the IAP) suggest that conjugate margin evolution may have been asymmetric.

Magíster en Ciencias de la Ingeniería, Mención Recursos y Medio Ambiente Hídrico / Ingeniero Civil / Debido a su naturaleza geológica, los acuíferos presentan gran variabilidad de los parámetros hidrogeológicos en cortas distancias. Sin embargo, debido a restricciones computacionacionales y a la imposibilidad de medir parámetros a pequeña escala, la modelación de estos sistemas usualmente se realiza utilizando grillas numéricas con celdas de tamaño mucho mayor que la escala de la heterogeneidad del acuífero, lo que afecta la representación de los campos de velocidades simulados, los cuales no contienen toda la información de pequeña escala o alta frecuencia. El impacto en la simulación del transporte de solutos se traduce en menores tasas de mezcla y dilución, lo cual puede generar menores tasas de reacción en el caso de transporte reactivo. Actualmente, se afronta este problema a través de métodos basados en el enfoque estocástico, en donde se utilizan conceptos probabilísticos para describir el flujo y el transporte en acuíferos. La teoría de la macrodispersión se basa en la descripción del movimiento de los solutos a través de las propiedades estadísticas del medio y busca cuantificar los efectos no modelados numéricamente. El coeficiente de macrodispersión de bloque efectivo ($D_b(t)$) está basado en esta teoría, y está definido de manera de capturar solo las fluctuaciones de velocidad de la escala inferior a la grilla numérica, modelando el efecto de éstas sobre la tasa temporal de deformación de plumas de soluto. Mientras se ha comprobado que la utilización del $D_b(t)$ reproduce la deformación de plumas bajo ciertos supuestos, su uso para representar la mezcla de solutos no se ha intentado hasta ahora. El objetivo de esta tesis es estudiar la posibilidad de extender la teoría del coeficiente de macrodispersión de bloque efectivo a procesos de mezcla para diversas condiciones de transporte. Para ello, se proponen dos metodologías para obtener un coeficiente de macrodispersión efectivo basado en el concepto del $D_b(t)$ para caracterizar correctamente la tasa global de mezcla. La primera metodología propone un coeficiente de macrodispersión efectivo que es constante, mientras que la segunda metodología propone un coeficiente que evoluciona temporalmente con la simulación. Los resultados obtenidos señalan que ambas metodologías son aplicables y presentan mejoras a la estimación de los procesos relacionados a la mezcla ocurridos en el medio permeable cuando se utiliza campos de velocidad que han perdido parte de su variabilidad numérica, obteniendo resultados satisfactorios para una amplia cantidad de parámetros y condiciones de transporte. Este trabajo permitió extender el concepto del $D_b(t)$ a procesos de mezcla, donde la metodología de cálculo podría utilizarse con aplicaciones futuras en remediación o estudios de ingeniería. A futuro, el método propuesto podría ser verificado y mejorado con datos reales de sitios contaminados.

Die Kopplung zwischen neuronaler Aktivität und cerebralem Blutfluss ist ein fundamentaler Prozess, der alle cerebralen Funktionen begleitet. Das Thema meiner Habilitation ist die Entdeckung einer neuen Ischämievariante, bei der neuronale Aktivierung eine cerebrale Ischämie auslöst, indem sich die Kopplung zwischen neuronaler Aktivierung und cerebralem Blutfluss umkehrt. Diese Umkehrung wird durch Produkte roter Blutkörperchen im Subarachnoidalraum hervorgerufen. Die eigentümlichste Eigenschaft dieser Ischämievariante ist ihre Wanderung im cerebralen Cortex gemeinsam mit der Welle neuronaler Aktivierung. Deshalb habe ich das Phänomen cortical spreading ischaemia genannt. Das vorgestellte tierexperimentelle Modell könnte für die verzögerten ischämischen neurologischen Defizite nach Subarachnoidalblutung Implikationen besitzen. Die Verbindung mit diesem klinischen Syndrom basiert auf: (a) der Induktion der cortical spreading ischaemia durch Produkte roter Blutkörperchen im Subarachnoidalraum, (b) der Übereinstimmung im Läsionsmuster mit corticalen ischämischen Infarkten, und (c) den therapeutischen Effekten von Nimodipin und mässiger hypervolämischer Hämodilution im klinischen Syndrom und im Tiermodell. Mit Hilfe dieses Modells ist es zum ersten Mal gelungen, experimentell die Hypothese zu bestätigen, dass Produkte roter Blutkörperchen eine cerebrale Ischämie induzieren können. Ich hoffe, dass das Modell dazu beitragen wird, neue Strategien bei der Behandlung von Patienten mit Subarachnoidalblutung zu entwickeln. / The coupling between neuronal activity and cerebral blood flow is a fundamental process, which underpins all cerebral functions. The topic of my Habilitation is the discovery of a new variant of ischaemia in which neuronal activation triggers a cerebral ischaemic event through the inversion of the coupling between neuronal activation and cerebral blood flow. This inversion occurs when red blood cell products are present in the subarachnoid space. The most distinct feature of this variant of ischaemia is its propagation in the cerebral cortex together with the wave of neuronal activation. Therefore, I named the phenomenon cortical spreading ischaemia . The presented animal model may have implications for the delayed ischaemic neurological deficits after subarachnoid haemorrhage. The link with this clinical syndrome has been based: (a) on the induction of cortical spreading ischaemia by red blood cell products in the subarachnoid space, (b) the correspondence between the characteristic patterns of the cortical ischaemic lesions, and (c) the therapeutic effects of nimodipine and moderate hypervolaemic haemodilution in clinical syndrome and animal model. With the aid of this model, it was possible to experimentally confirm the hypothesis that red blood cell products can induce cerebral ischaemia. I hope that the model will contribute to develop new strategies for the treatment of patients with subarachnoid haemorrhage.

A very important aspect for the functioning of an organism is that cells adapt their behaviour to external stimuli. They continuously interact with their environment, and biochemical and physical cues can activate cellular signalling, which leads to changes in cell behaviour such as proliferation and shape. Understanding cells' interactions with their environment is also important for understanding diseases. For example mechanosensing, which is the sensing of the cell's mechanical environment, has been associated with cancer development. In order for a cell to be able to sense its mechanical environment, it needs to form attachments to the environment. In my thesis, I have worked on three different tasks: the development of a new measurement technique and the study of initial cell adhesion and of cell spreading. When a cell from suspension first comes into contact with a substrate, it forms initial attachment bonds with proteins on the substrate surface. These bonds are mediated through integrins, which are transmembrane heterodimers, binding to the cell's environment on one side and to the cell's cytoskeleton on the other side. I study this initial cell attachment by measuring the force needed to detach cells, called cell adhesion strength. For these experiments I built a detachment device, which allows the detachment of cells from a substrate by vibrating the substrate in liquid. The device combines cell incubation, detachment and imaging. I measured the dependence of initial integrin bond formation on external factors such as incubation temperature and substrate stiffness. Once initial integrin bonds are formed, many different proteins are recruited to the adhesion site in order to form stronger adhesions. Amongst these proteins are signalling proteins, which direct the behaviour of the cell as a whole. One of the first cellular reactions to a substrate after initial integrin binding is cell spreading. This can be seen by the cell changing its shape from spherical to dome-like on the substrate. Because cell spreading is a very early response of a cell to a substrate, the onset time of spreading can be used as a quantitative measure for the time it takes the cell to sense a substrate and signal shape change. In my work, I look at the distribution of the time of initial cell spreading in a population of cells. I measure this distribution under different growth conditions such as pH, change of incubation medium from DMEM to PBS, substrate stiffness and incubation temperature. In my detachment experiments, I observe that vibration accelerates cell spreading in those cells which remain on the substrate. This is a connection between the detachment experiments and the cell spreading experiments and it shows how cells react to external forces. By changing the medium temperature in the cell detachment and cell spreading experiments, I am able to analyse the kinetics of these two processes. I use a signalling network model to analyse the internal cellular signalling path that leads from a spherical to a spread cell.

Migraine affects ~15% of the US population (nearly 40 million people), making it one of the most common neurological disorders; however currently available therapeutic options for migraine relief are often ineffective. Moreover, acute and prophylactic drugs are both commonly associated with contraindications and serious side effects, and routine use of acute treatments may result in medication overuse-headaches. Elevated levels of the neuropeptide calcitonin gene-related peptide (CGRP) are known to be a primary factor in migraine pathogenesis, although the mechanisms by which CGRP expression becomes errantly modulated are unclear. CGRP is a product of the trigeminal ganglion and can be released both peripherally onto the dura mater, leading to neurogenic inflammation, and centrally at the spinal trigeminal nucleus, leading to neuromodulation. A great deal of CGRP-relevant migraine research has focused on the trigeminovascular system, but whether the cerebral cortex may have a role in migraine pathophysiology been less well studied. A subset of migraineurs experience a premonitory aura, which often manifests as a disturbance in one visual hemifield. An aberration called cortical spreading depression (CSD) is the likely electrophysiological substrate of the migraine aura, but whether CSD and CGRP are functionally related is not known. CSD is characterized by an initial transient wave of neuronal and glial depolarization, followed by a prolonged period of quiescence that is largely refractory to subsequent stimulation. Converging evidence supports a facilitatory role for cortical spreading depression (CSD) in migraine with and without aura, and CSD propagation has been shown to be dependent on functional CGRP receptors. Moreover, reported effects of CSD overlap with those of CGRP-mediated neurogenic inflammation. The experiments described herein seek to test the hypothesis that induction of CSD in vivo will lead to increased CGRP expression in the rodent cerebral cortex. Preliminary data in rats suggests that 3M KCl-induced CSD can trigger increased CGRP expression in the ipsilateral cortex. Preliminary data in mice has been less conclusive. Presented here are the data obtained from mice and rats, as well as speculation on the cause(s) of the differences in CGRP expression between species and how these findings relate to human studies.