Ingeniero Civil Eléctrico / El auge que ha presentado en los últimos años la Astronomía observacional en Chile, producto de las inigualables condiciones ambientales del desierto de Atacama, ha generado la necesidad de desarrollar tecnologías afines con este gran desafío. Este trabajo propone soluciones en el área de procesamiento digital de señales haciendo uso de procesadores de alta velocidad. En concreto, se diseña e implementa un espectrómetro de ancho de banda seleccionable para aplicaciones en espectrometría de alta resolución como lo es el estudio de estructuras moleculares híper finas. Además se diseña un bloque de control de datos, útil entre otras cosas para mejorar las mediciones de rechazo de banda lateral. El uso de procesadores FPGA (Field Programmable Gate Array) permite implementar espectrómetros digitales. Estos diseños son aplicables en procesadores cada vez más veloces. Existen arquitecturas prediseñadas para estos propósitos como por ejemplo la plataforma ROACH (Reconfigurale Open Architecture Computing Hardware) creada por CASPER (Collaboration for Astronomy Signal Processing and Electronic Research) y que se utiliza en este trabajo de título. Utilizando diseños en ambiente MATLAB Simulink se crea un ejecutable que da instrucciones al FPGA. Así, estos diseños son controlados y comandados por códigos en lenguaje Python, los que realizan un post procesamiento de los datos para su posterior análisis. Los diseños creados para mejorar el rechazo de banda lateral demuestran ser efectivos limitando la contaminación de banda adyacente a menos de -50dB. El bloque de control asegura el buen funcionamiento del sistema, incluso en presencia de alto ruido de fase. Por otro lado al realizar acercamiento a una porción del ancho de banda se logra una mejor resolución espectral logrando distinguir variaciones de energía en rangos pequeños de frecuencia. A futuro, todos los diseños creados en este trabajo pueden implementarse a mayor velocidad, utilizando procesadores más avanzados. Es posible enriquecer el zoom, reduciendo el ancho de banda desde dos hasta ocho veces, y utilizar mezcladores digitales para seleccionar una zona arbitraria del espectro.

En muchas universidades y centros de investigación a nivel mundial, se han realizado experimentos con elementos de concreto armado. Esto se ha hecho con el fin de poder investigar su comportamiento ante diversas variables planteadas. Con el ánimo de investigar el comportamiento no lineal de vigas de concreto armado, la presente tesis tiene como objetivo realizar ensayos monotónicos de flexión a cuatro vigas de concreto armado con distintas cuantías de acero negativo obtenidas mediante redistribución de momentos. Esto se realizará con el fin de poder lograr, en cada caso, un mecanismo plástico completo que nos permita estudiar las suposiciones teóricas respecto a la capacidad resistente de las vigas, mecanismos plásticos, comportamiento en estado de servicio y último. El estudio experimental estuvo conformado por cuatro vigas de concreto armado de 200x300 mm de sección y 2900 mm de longitud libre entre apoyos. Se asumió un modelo empotrado – apoyado con una carga puntual al centro de la luz. Esta se incrementó desde cero hasta la carga límite de falla en compresión del concreto. La variable de estudio fue la cuantía de acero negativo, la cual fue disminuida desde una viga base (3ϕ5/8’’) en un 20%,30% y -20% (aumentado en 20%) mediante redistribución de momentos. Los estribos para todas las vigas fueron de 6 mm espaciados cada 100 mm. Los resultados indican que incluso con un 30% de redistribución (superior al límite de la norma peruana) se puede lograr un comportamiento en servicio adecuado y similar a la viga sin redistribución en cuanto a deflexiones y agrietamiento, para los cuales se obtuvo 7.9 mm (menor a L/300) y 0.35 mm (menor a 0.40 mm) respectivamente. La resistencia máxima se vio reducida en un 5% respecto a la viga base pero fue reemplazada por una mayor capacidad de deformación ante carga última (deflexiones de hasta 92 mm) / Tesis

Amyotrophic Lateral Sclerosis (ALS) is a debilitating and fatal neurodegenerative disease affecting upper and lower motor neurons. Though studied for over two decades since the first ALS-associated genetic mutation was discovered, researchers have yet to uncover the pathological processes that lead to progressive degeneration of motor neurons in ALS, or to develop effective treatments. One prominent hypothesis proposes that excitotoxicity caused by increased motor neuron firing plays a role in ALS pathogenesis. While prior studies reported increased action potential firing in early postnatal ALS-model motor neurons in vivo, it remains unknown whether the increased activity stems from increased intrinsic excitability of ALS motor neurons or from increased excitatory drive, and whether these changes are transient or persist into adulthood, when ALS symptoms emerge. In this thesis, I circumvented the difficulties in standard measurement of electrophysiological properties of adult spinal motor neurons in vivo by relying on the visualization of the axon initial segment, a subcellular structure known to undergo compensatory structural changes in response to perturbations in excitatory input. I discovered that cultured motor neurons derived from stem cells of the SOD1G93A mouse model of ALS display shortened axon initial segments and hypoexcitable electrophysiological properties. The shortening of the axon initial segment is compensatory, as ALS motor neurons receive increased numbers of excitatory inputs and manifest increased spontaneous activity. Remarkably, similar shortening of the axon initial segment was detected in early presymptomatic spinal motor neurons in vivo. The shortened axon initial segment persists into the symptomatic stages and is particularly pronounced in motor neurons containing p62 immunoreactive aggregates and neurons exhibiting swollen mitochondria, two signs of stress and neurodegeneration in the disease. Based on these observations I propose that early in the presymptomatic stages of the disease, spinal motor neurons recruit excessive excitatory inputs, resulting in their increased activity that is in part compensated by shortening of the axon initial segment. This state persists and becomes even more pronounced in motor neurons exhibiting biochemical changes preceding neurodegeneration. While these observations support the potential role for excitotoxic stress in spinal ALS motor neurons, I paradoxically observed the opposite phenotype in ALS-vulnerable cranial motor neurons in the brainstem of the SOD1G93A animals, raising the possibility that the cellular stress that drives the neurodegeneration in ALS is motor neuron subtype specific.

The development of the diencephalon can be summarised as a process in which cells that initially appear similar give rise to a complex structure that contains a variety of cell groups called nuclei. It involves two stages: the early patterning of the diencephalic prosomeres and the later formation of the individual nuclei. It has been shown that transcription factors and morphogens regulate the first stage but their further effects on the second stage remain unclear. The ventral lateral geniculate nucleus (vLGN) is involved in the visual system and is shown to have complex origins from the thalamus, the zona limitans intrathalamica (ZLI) and the prethalamus. The transcription factor Pax6 is involved in the development of brain structures including the cortex, the diencephalon and the major axonal tracts in the forebrain by playing a multifaceted role in patterning, proliferation, differentiation, migration and axon guidance. It is known that Pax6 is essential in setting up the prosomeric boundaries in the developing diencephalon but its role in the formation of individual nuclei has not yet been explored. By using a conditional Pax6 knock-out mouse driven by Zic4Cre with a green fluorescent protein (GFP) reporter showing the Cre activity, the formation of the thalamic nuclei vLGN, dorsal lateral geniculate nucleus (dLGN) and VP (ventral posterior nuclei) was examined in postnatal day 0 (P0) Pax6+/+, Pax6fl/+ and Pax6fl/fl pups. Using this mouse model, I found an increase in nuclear volume at the rostral level and a global decrease in cell density in the P0 Pax6fl/fl vLGN, whereas in the dLGN an increase of GFP+ve cell proportion was observed. In Pax6fl/+, I found an increase in GFP+ve cell proportion in the caudal part of the vLGN and across the dLGN. No significant change was observed in the VP in either the Pax6fl/+ or the Pax6fl/fl. The defects in the vLGN and dLGN could be caused by: 1. disruption of the expression of patterning factors such as Shh and Nkx2.2; 2. cell proliferation defcts and abnormal apoptosis; 3. ocular developmental defects; 4. failure in cell sorting/migration; 5. cell fate change. During my PhD, I tested the first three theories and explored the fourth but was not able to pursue the last due to the time limit of the project. To test the hypothesized mechanisms underlying those defects seen in the vLGN and dLGN, I performed BrdU labelling to study the time origin of cells that contribute to these two nuclei and discovered that E11.5 and E12.5 are the main ages when these cells and the GFP+ve subpopulation are born. Then I carried out experiments to examine the cell proliferation and cell apoptosis in the thalamus (pTH-R, rostral part of the progenitor zone of the thalamus, and pTH-C, caudal part of the progenitor zone of the thalamus) and the prethalamus (Pth) from E11.5 to E13.5 and found: 1. the proliferation rate decreased in the pTH-R in Pax6fl/+ at E11.5; 2. the growth fraction decreased in both pTH-C and pTH-R in E12.5 Pax6fl/fl; 3. there is no change in cell proliferation in the GFP+ve subpopulation; 4. no abnormal apoptosis is observed in either the whole cell population or the GFP+ve subpopulation. Judging by the amplitude of the change in proliferation in the pTH-R and pTH-C at E11.5 and E12.5, it is unlikely that these changes alone are responsible for the phenotypes seen in P0 vLGN and dLGN. Then I examined the expression patterns of Shh and Nkx2.2 and the expansion of both was observed in Pax6fl/fl at both E12.5 and E13.5, which could explain the volume change of the vLGN but not the change in the proportion of GFP+ve subpopulation in both the vLGN and dLGN. Then I continued to examine if the ocular input from the retinal ganglionic cells are severely affected by the deletion of Pax6 and found no gross change in the conditional mutants, which rejected the ocular developmental defects theory. At the end of my PhD, I performed a BrdU short-term survival experiment and a brain slice culture combined with live imaging experiment to explore the possibility of abnormal cell migration causing the vLGN and dLGN phenotypes and found that the cells moving along the border of the thalamus and prethalamus move faster in the Pax6fl/fl than in the Pax6fl/+, but rather than moving directly toward the lateral surface of the diencephalon, they take a detour. These findings indicate that the deletion of Pax6 causes minor changes in the proliferation of E11.5 to E13.5 diencephalon and expansion of regional marker expression such as Shh and Nkx2.2, which could potenially affect the volume and change the proportion of GFP+ve cells in P0 vLGN and dLGN. Migration defects caused by Pax6 could also contribute to the phenotype observed in those two nuclei. Potential cell fate change caused by Pax6 deletion could be another factor that contributes to the defects in the conditional mutants. More work needs to be done to test the migration defect and cell fate change hypotheses in future.

Built-up steel I-girders are very commonly used in bridge construction. Their spans are typically very long, and they are susceptible to lateral torsional buckling if not enough lateral support is provided. This thesis includes guidelines for preventing lateral torsional buckling of steel I-girders under dead and wind load, accompanied with finite element analysis of double girder systems. The first portion includes capacity envelopes for single girders with single and double symmetric cross sections under various loading conditions and boundary conditions for double and single symmetric cross sections with double girders subjected to dead loads only. The second portion is dedicated to finite element analysis of double girders. Buckling analyses have been conducted on single symmetric double girders to verify their capacity equations and investigate the behavior of double girders subjected to wind load. The analyses focus on the weak axis bending of the double girder system as a whole and an evaluation of whether buckling of cross-bracing is an issue when lateral loads are present.

Driving a horizontal roadway curve requires a change in vehicle alignment and a potential reduction in speed. Curves may present a challenging situation during adverse conditions or to inattentive drivers. Chevron signs provide advanced warning and positive guidance throughout the curve. Some agencies place supplemental retroreflective material on sign posts to enhance the signs? conspicuity and visibility. The objective of this study was to determine any incremental benefits in vehicle speed and lateral lane position when retroreflective material was applied to Chevron sign posts (ChevFull). This study analyzed three separate evaluation scenarios in a before, after, and after-after experimental design. There was an existing Baseline evaluation with no vertical delineation, a standard Chevron evaluation, and an experimental ChevFull treatment evaluation. Data collection measured vehicle speed and lateral position data at the point of curvature and mid-point on two separate curves. Findings showed that both Chevrons and the ChevFull treatment moved vehicles away from oncoming traffic by about 15 inches. Overall, there was little difference between the lateral position findings of the two Chevron treatment scenarios. Chevrons achieved a 1.28 MPH reduction in mean vehicle speed from the Baseline evaluation and the ChevFull treatment obtained a 2.20 MPH reduction. The findings determined that the benefits of the ChevFull treatment were not substantial. The author recommends that the MUTCD should continue to present the ChevFull treatment as an optional delineation tool. Based on this research, the author does not recommend any changes to the MUTCD.

Thesis (M.S.)--Brigham Young University. Dept. of Civil and Environmental Engineering, 2004. / Includes bibliographical references (p. 215-220).

Anoplocephala perfoliata is a species of parasitic worm that belongs to a group known as cestodes, which specifically target equine animals. As with all types of tapeworms, these parasites infect the gastrointestinal tract of their host, with devastating and potentially fatal consequences. The current lack of a sensitive and specific test for this parasite means that it continues to go undetected, hense this project aims to develop a novel and rapid diagnostic test with high sensitivity and specificity to help increase detection, thus precluding economic loss in the equine industry. The project details the development of three unique detection platforms; an ELISA, a lateral flow assay and an impedimetric immunosensor, aimed to detect IgA in saliva, since IgA is the dominant immunoglobulin of the mucosal immune system. IgA was therefore believed to be the ideal marker for rapid, specific and early indication of infection with A. perfoliata. Diagnosis using saliva samples was an integral part of this project, since it would allow for non-invasive sampling, by non-skilled personnel. A highly sensitive ELISA-based detection system was developed in this project for the detection of 3 different types of IgA. The first ELISA was developed to detect non-specific or ‘total’ IgA levels. Using a sandwich ELISA format, IgA was detectable with a LoD of ~0.04 ng/ml. A second ELISA was developed using the crude excretory/secretory (E/S) antigen, cultured from A. perfoliata worms, which were obtained by a vet during post-mortem examination of infected horses. The crude antigen mix was then used to fabricate an ELISA to detect specific IgA in saliva, produced against the E/S antigens. The crude antigen was then employed in a series of SDS PAGE and western blot experiments, which revealed the 12/13 kDa antigen as the main antigen detected by IgA in saliva. The 12/13 kDa was then electroeluted and used to immunise rabbits, in order to obtain anti-12/13 kDa antibodies, which were later used to purify large quantities of the 12/13 kDa antigen from the crude antigen mix. This allowed for the fabrication of the third and final ELISA, to detect IgA specific to the 12/13 kDa antigen. The 3 ELISAs were optimised throughout this project to ensure the most ideal conditions, such as antibody concentrations, sample dilutions, sample diluents, incubation temperatures and times were employed to obtain maximum assay sensitivity, specificity and productivity in a commercial setting. Testing samples (n = 24) using all 3 ELISAs and then standardising the specific IgA levels against the non-specific IgA, allowed for a novel and reliable detection method for A. perfoliata to be developed. This diagnostic test was developed in partnership with Austin Davis Biologics Ltd., who in April 2014 launched a screening programme which now offers horse owners an accurate means of testing their horses for A. perfoliata infections accurately. The second detection platform developed during this project was a lateral flow assay, whereby an immunochromographic strip was used to measure IgA levels in saliva. The studies performed determined the optimal conditions as using 40 µl of a 1:1,000 dilution of saliva using PBS(T) 1% as the sample diluent. The capture and control antibody were used at a concentration of 0.2 mg/ml, which were coated on the nitrocellulose membrane using an automated dispensing system (BioDot). The conjugate was labelled using gold nanoparticles, since it does not require any substrates or wash steps and its aggregation allows for immediate visual detection. A LoD of ~47 ng/ml was obtained for this assay. The final detection system investigated as part of this project was a label-less impedimetric immunosensor, whereby IgA was detected by means of electrochemical impedance spectroscopy (EIS). Polyaniline was the conductive polymer chosen to coat the surface of the screen printed carbon electrode, since the amine groups could be utilised to immobilise biotin molecules. A biotin-avidin complex was employed to ensure the uniform immobilisation of the capture antibody. Using the capture and control antibody at a concentration of 50 µg/ml and 10 mM ferri-ferrocyanide as the redox solution, IgA concentrations over a range of 100 – 0 ng/ml were investigated by Electrochemical Impedance Spectroscopy (EIS).

Biocuration is manual scientific collection, annotation and validation of literary information of biological and model organisms into a single database. Successful biocuration processes involve those with an extensive collection of literature, a user-friendly database interfaces for entering and analyzing data from published papers, and highly regulated training and quality assurance protocols. Due to the rapid expansion of biomedical literature, an efficient and accurate biocuration process has become more valuable due to the magnitude of data available in published literature. As the biocuration process incorporates undergraduates, it is critical that the medium for data collection is simple, ergonomic, and infallible. A reconstructed FileMaker Pro database was introduced to previously trained undergraduate students for process evaluation. Streamlining the biocuration process and grouping data structure to be more intuitive were two goals the new database interface hoped to achieve. The creation of a rigorous training program and strict quality management protocol is needed to prepare the lab for the introduction of efficient biocuration processes. Through the database designing process, training protocols were drafted to effectively call the biocurator’s attention to important changes in the interface design. Upon prototyping the database, entry errors were reviewed, training protocols were adjusted, and the quality protocols were drafted. When the combination of undergraduate biocurators and the reconstructed database under these new protocols was compared to statistics in the biocuration field, results proved to show increase in both productivity rates as well as accuracy rates. By having such efficiency at the undergraduate level, subject matter experts will no longer be required to perform this type of research and can focus on analysis. This will increase research productivity and reduce costs in the overall biocuration process. With over 12,000 published papers regarding Amyotrophic Lateral Sclerosis on Pubmed in 2014 alone, this revolutionary combination could lead to quickly finding a suitable cure for these patients.

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