In the Basin and Range province of southwestern North America, Oligocene and Miocene normal faults are superimposed upon the Late Cretaceous-early Tertiary magmatic arc. This study examines tilted fault blocks containing dismembered pieces of porphyry systems, including pieces below and peripheral to ore bodies, that are exposed at the modern surface. Features in the magmatic-hydrothermal porphyry systems are used to place constraints on the style of extension in Arizona, and reconstructions of extension are used to examine the deep and peripheral portions of porphyry systems to provide a more complete understanding of porphyry systems as a whole. The Eagle Pass, Tea Cup, and Sheep Mountain porphyry systems of Arizona are examined in this study. In all the study areas, previous interpretations of the style of extension involved strongly listric normal faults. However, similar amounts of tilting observed in hanging wall and footwall rocks, as well as structure contour maps of fault planes, require that down dip curvature on faults was minimal (<1°/km. Instead, extension is shown here to have occurred as sets of nearly planar, "domino-style" normal faults were superimposed upon one another, including in the Pinaleño metamorphic core complex. Reconstructions of Tertiary extension reveal that sodic (-calcic) alteration is occurs 2-4 km peripheral to, and greisen alteration is found structurally below and overlapping with, potassic alteration. In addition, a preliminary reconstruction of extension across the Laramide magmatic arc reveals that the geometry, as revealed by known porphyry systems, is of similar scale to that of other magmatic arcs. These results help further the debate surrounding competing models of continental extension, and combine with previous work to provide a more complete understanding of the geometries of Arizona porphyry systems at the district and arc scale.

In Chapter 2, we consider the hydrostatic equilibrium figure of a rotating earth model with arbitrary radial density profile. We derive an exact non-linear partial differential equation describing the equilibrium figure. Perturbation theory is used to obtain approximate forms of this equation, and we show that the first-order theory is equivalent to Clairaut's equation. In Chapter 3, a method for parametrizing the possible equilibrium stress fields of a laterally heterogeneous earth model is described. In this method a solution of the equilibrium equations is first found that satisfies some desirable physical property. All other solutions can be written as the sum of this equilibrium stress field and a divergence-free stress tensor field whose boundary tractions vanish. In Chapter 4, we consider the minor vector method for the stable numerical solution of systems of linear ordinary differential equations. Results are presented for the application of the method to the calculation of seismic displacement fields in spherically symmetric, self-gravitating earth models. In Chapter 5, we present a new implementation of the direct solution method for calculating normal mode spectra in laterally heterogeneous earth models. Numerical tests are presented to demonstrate the validity and effectiveness of this method for performing large mode coupling calculations. In Chapter 6, we consider the theoretical basis for the viscoelastic normal mode method which is used in studies of seismic wave propagation, post-glacial rebound, and post-seismic deformation. We show how the time-domain solution to the viscoelastodynamic equation can be written as a normal mode sum in a rigorous manner.

Since its introduction in 1999, bounded model checking (BMC) has quickly become a serious and indispensable tool for the formal verification of hardware designs and, more recently, software. By leveraging propositional satisfiability (SAT) solvers, BMC overcomes some of the shortcomings of more conventional model checking methods. In model checking we automatically verify whether a state transition system (STS) describing a design has some property, commonly expressed in linear temporal logic (LTL). BMC is the restriction to only checking the looping and non-looping runs of the system that have bounded descriptions. The conventional BMC approach is to translate the STS runs and LTL formulae into propositional logic and then conjunctive normal form (CNF). This CNF expression is then checked by a SAT solver. In this thesis we study the effect on the performance of BMC of changing the translation to propositional logic. One novelty is to use a normal form for LTL which originates in resolution theorem provers. We introduce the normal form conversion early on in the encoding process and examine the simplifications that it brings to the generation of propositional logic. We further enhance the encoding by specialising the normal form to take advantage of the types of runs peculiar to BMC. We also improve the conversion from propositional logic to CNF. We investigate the behaviour of the new encodings by a series of detailed experimental comparisons using both hand-crafted and industrial benchmarks from a variety of sources. These reveal that the new normal form based encodings can reduce the solving time by a half in most cases, and up to an order of magnitude in some cases, the size of the improvement corresponding to the complexity of the LTL expression. We also compare our method to the popular automata-based methods for model checking and BMC.

G protein-coupled receptors (GPCRs) form a link between the cell and their environment when signaling pathways are activated upon ligand binding. However, the ligands and functions for many GPCRs remain to be determined. G protein-coupled receptor 50 (GPR50) is one such orphan, and its exact role is yet unknown. There is however emerging functional and genetic evidence suggesting a function for GPR50 in psychiatric illness and lipid metabolism. It was hypothesised that investigating GPR50’s protein-protein interactions would lead to a greater understanding of the role of GPR50 in normal brain functioning and in mental illness. Putative protein interactors were initially isolated by a yeast two-hybid study and were further tested here. To address GPR50’s links to mental illness, the GPR50∆502-505 deletion variant associated with mood disorders was also investigated. To test this hypothesis I sought to confirm some of the key yeast two-hybrid interactions. Using co-immunoprecipitation and immunocytochemistry the interaction of GPR50 with reticulon family members Nogo-A, Nogo-C and RTN3, and with cell-cell adhesion molecule CDH8 and lipid-associated protein ABCA2 were validated. In order to identify the location of interactions, subcellular fractionation of mouse brain and rt-PCR and immunohistochemistry in developing and adult mouse brain were performed. GPR50 and several interactors were found to be enriched at the synapse by subcellular fractionation of whole adult brain, and at embryonic day 18 (E18) and 5 weeks by rt-PCR. Colocalisation of GPR50 and interactors was found in the amygdala, hypothalamus, cortex and specific brain stem nuclei by immunohistochemistry. The discovery of GPR50 expression in noradrenergic, serotonergic and dopaminergic nuclei in the adult brain stem suggests a further role for GPR50 in neurotransmitter signaling and stress. To investigate the function of GPR50 two assays were performed that measure processes which are known to be affected by Nogo and RTN3: The first assay was a neurite outgrowth assay in Neuroscreen-1 cells, a PC12 cell clone. A significant increase in neurite length was detected after transient overexpression of GPR50 and this effect was increased in the GPR50∆502-505/T532A variant. Additionally GPR50-overexpression resulted in an increase in filopodia formation suggesting a role in actin dynamics. As a second functional assay in vitro BACE1 activity assays were performed in HEK293 cells. GPR50 but not GPR50∆502-505/T532A overexpression resulted in a significant increase in BACE1 activity. Lastly a final series of pilot experiments were performed to gain insight into the secondary structure of the C-terminal domain and the effects of the polymorphisms on structure. The 35kDa GPR50 C-terminal domain was purified and Circular Dichroism studies indicated a predominantly unstructured protein with increased a- helical content in the GPR50∆502-505 variant. The results in this thesis indicate a role for GPR50 in neuronal development and synaptic functioning. The results also strengthen an association with major mental illness, with links to several disease mechanisms.

Very long and noisy sequence data arise from biological sciences to social science including high throughput data in genomics and stock prices in econometrics. Often such data are collected in order to identify and understand shifts in trends, for example, from a bull market to a bear market in finance or from a normal number of chromosome copies to an excessive number of chromosome copies in genetics. Thus, identifying multiple change points in a long, possibly very long, sequence is an important problem. In this article, we review both classical and new multiple change-point detection strategies. Considering the long history and the extensive literature on the change-point detection, we provide an in-depth discussion on a normal mean change-point model from aspects of regression analysis, hypothesis testing, consistency and inference. In particular, we present a strategy to gather and aggregate local information for change-point detection that has become the cornerstone of several emerging methods because of its attractiveness in both computational and theoretical properties.

<p>For any Legendrian knot in R^3 with the standard contact structure, we show that the existence of an augmentation to any field of the Chekanov-Eliashberg differential graded algebra over Z[t,t^{-1}] is equivalent to the existence of a normal ruling of the front diagram, generalizing results of Fuchs, Ishkhanov, and Sabloff. We also show that any even graded augmentation must send t to -1.</p><p>We extend the definition of a normal ruling from J^1(S^1) given by Lavrov and Rutherford to a normal ruling for Legendrian links in #^k(S^1\times S^2). We then show that for Legendrian links in J^1(S^1) and #^k(S^1\times S^2), the existence of an augmentation to any field of the Chekanov-Eliashberg differential graded algebra over Z[t,t^{-1}] is equivalent to the existence of a normal ruling of the front diagram. For Legendrian knots, we also show that any even graded augmentation must send t to -1. We use the correspondence to give nonvanishing results for the symplectic homology of certain Weinstein 4-manifolds.</p> / Dissertation

El proyecto de Título respaldado en esta Memoria consiste en un conjunto urbano emplazado en la ciudad de Santiago. Más que el proyecto en sí, lo más valioso que se propone es establecer un nuevo vínculo entre el medio construído y el medio natural circundante, a través de una debida comprensión de los componentes y fenómenos propios de la cuenca de Santiago. Los ejes naturales de este valle donde se emplaza la ciudad, son sus Cursos de Agua. Por lo mismo el objetivo es establecer integración, con las herramientas propias de la Arquitectura. Los espacios y recintos propuestos para esta integración contemplan distintos grados de aproximación a esta intervención, entendiendo que usuarios ajenos al borde del rio, tienen una relación distinta a la de un residente del conjunto. Es en estos últimos donde se enfatiza la experiencia de vivir “en la ribera” y no en otro lugar de la ciudad, construyendo así una suerte de “conciencia colectiva” de residir en un subsistema del río. Entendiendo la tendencia a la escasez de agua como problemática global, y las consecuente estrategias para su preservación, es que se entiende un Sistema de Reciclaje de Aguas Domicialiarias, como órgano irrigador de una serie de instalaciones en la línea de esta temática: “La Arquitectura del Agua”. La disponibilidad permanente de agua es aprovechada en dos frentes: _ en usos recreativos (como bañadores, piletas, caídas de agua, estanques, etc.) _ para un amplio abanico de posibilidades de diseño, vinculados a las áreas verdes, las especies de alta demanda (como superficies de pasto y arbolado en altura), como la disponibilidad de vegetación asociada a estructuras habitables, como fachadas verdes, etc.

Pathogenic gain-of-function mutations associated with increased paternal age, albeit harmful to embryonic development, are paradoxically enriched in the normal testis. Evidence from previous studies indicates that these so-called paternal age-effect mutations confer a proliferative advantage to the spermatogonia in which they arise, leading to clonal expansion within the normal testis over time. Recently, spermatocytic seminoma (SS; a rare testicular germ cell tumour that occurs mainly in older men) has emerged as a key link between the processes of somatic and germline mutation (Goriely et al, Nat Genet. 41:1247-52, 2009), suggesting that the proposed clonal expansion events can in some cases lead to testicular tumourigenesis. In this thesis, I have used immunohistochemistry to seek evidence for putative clones of cells in the normal adult testis. To address this, a screening approach was developed using markers chosen from analysis of normal testicular tissues and SS. The ontogeny of OCT2 and SSX expression in human testis, from embryonic development to adulthood, identified distinct subpopulations of spermatogonia at different maturation stages. Together, these data reveal the potential of OCT2 as a novel marker of A_dark spermatogonia (human reserve spermatogonial stem cells). In parallel with these observations, two distinct types of SS characterised by differential OCT2 and SSX immunoexpression were identified, providing new evidence for heterogeneity of this tumour. This work provided the backdrop to the detailed immunohistochemical study of normal adult testis by characterising in serial sections the expression of five spermatogonial markers, MAGEA4, SSX, FGFR3, OCT2 and SAGE1, and a proliferation marker, Ki67. Independent sections were screened with predetermined criteria set to identify unusual positively-stained cellular clusters within the seminiferous tubules. Several antigenic combinations previously described in SS were observed in a subset of these clones, suggesting differing genetic origins and a possible link with early events of testicular tumourigenesis. The size (minimum number of cells) of each clonal event was estimated and its correlation with the staining pattern of the molecular markers was investigated. In summary, the data presented in this thesis convincingly identify for the first time the previously hypothesised clonal events in the testis using immunohistochemical markers. My research will pave the way for future work involving genetic analysis of microdissected cells from these putative clones, aimed at identifying the underlying mutational events thought to be present.

This thesis is designed to emphasize and illustrate that marginal costing is a tool of management that can make clear the how, when, why, and wherefor of the price determining affect and its results.

In the present study, parameter estimates, standard errors and chi-square statistics were compared using normal and elliptical estimation methods given three research conditions: population data contamination (10%, 20%, and 30%), sample size (100, 400, and 1000), and kurtosis (kappa =1,10, 20).