Los dispositivos CCDs (por las siglas en inglés de Charge Coupled Devices) son aún hoy en día la tecnología líder para la toma de imágenes de baja distorsión y son ampliamente utilizados en aplicaciones de astronomía en el rango de la luz visible y en el infrarrojo cercano. En esta tesis se estudia y desarrolla su utilización para la detección de otras partículas diferentes a los fotones de luz, en particular para partículas con muy poca probabilidad de detección y muy poca deposición de energía logrando que esta nueva tecnología presente una ventaja respecto a detectores disponibles hoy en día. Los resultados de esta tesis son la base del desarrollo de una aplicación de un sistema de CCDs para la detección de neutrinos provenientes de un reactor nuclear. Se estudian las características principales de los CCDs que los hacen aptos para esta novedosa aplicación, y se encuentra que la mayor limitante de su rendimiento es el ruido de lectura agregado por su etapa de salida. Se desarrolla una técnica para reducir su incidencia, y mejorar así la capacidad de detección. A partir de estas características se analiza la capacidad de los CCD para detectar neutrinos provenientes de un reactor nuclear por medio de la interacción coherente entre el neutrino y los núcleos de los átomos de silicio. Para optimizar la detección de eventos de este tipo en las imágenes de salida, se deriva un modelo matemático que estudia el mecanismo de generación de carga en el CCD y se desarrolla una técnica de calibración que permite obtener información de la profundidad a la que se produce la ionización Estos resultados se plasmaron en el desarrollo de un prototipo instalado en la Central Nuclear Almirante Álvaro Alberto, en Angra dos Reis, Brasil. Se muestran algunos resultados preliminares obtenidos con este prototipo, y se comentan las mejoras que se realizarán próximamente en este sistema. / Charge Coupled Devices are still nowadays the best available technology for low distortion digital imaging applications and are extensively used for ground and spacebased astronomy for visible light and near infrared. In this thesis, studies to extent its use to applications for the detection of particles different to light photons are presented, in particular for those particles having low probability of interaction and small deposition of energy for which this technology presents advantages over available detectors. These studies are the base for the development of a CCD system aiming the detection of low energy neutrinos coming out from a nuclear reactor. The most important aspects of scientific CCDs for particle detection are revisited, and its main detection limitation produced by the readout noise added by the output amplifier of the device is explained. A technique to reduce the effect of this noise and to improve the detection performance is developed. The main features of CCDs are then used to analyze the feasibility of detecting low energy neutrinos through their coherent scattering with nuclei. A mathematical model of the expected signal in the output images is obtained and a new technique for the calibration of the CCDs to obtained the depth of the interaction in the silicon is developed. This result is used to improve the detection performance of the system The first CCD system prototype for this application is presented together with some details of its installation at Central Nuclear Almirante Alvaro Alberto in Angra dos Reis, Brazil, and some preliminary results are discuSSED.

<p>Ligand binding can modulate function of proteins and nucleic acids by changing both the populations of functionally distinct conformational states and the timescales on which they interconvert. For this reason, both thermodynamic and kinetic details of coupling can be important to proper function. How tightly does ligand bind to the different conformational states? What effect does ligand binding have on the conformational equilibrium and conformational kinetics? On what timescales and in what order do binding and conformational change occur? Using a combination of stopped-flow kinetics, isothermal titration calorimetry, and x-ray crystallography, we determine the mechanisms of coupled binding and conformational change in protein (Bacillus subtilis RNase P protein) and RNA (DP17 biosensor) systems. </p><p>The results demonstrate that rigorous kinetic analysis can be used to estimate the equilibrium and rate constants for conformational changes, as well as the affinities of ligands for different conformational states. A single ligand can bind to different conformational states of the same protein or nucleic acid with affinities that differ by orders of magnitude. This binding shifts the conformational equilibrium towards the higher affinity state through a combination of increasing rate constants for the forward conformational change and decreasing rate constants for the reverse conformational change. Using a flux-based analysis of the mechanisms we show that molecular recognition is kinetically partitioned between a number of pathways that differ by the order in which binding and conformational change occur. The absolute and relative flux through these pathways varies with ligand concentration, the affinities of the ligand for the various conformational states, and the ability of ligand to accelerate the conformational change. Together, the results give insights into how biological function depends on the kinetic and thermodynamic details of coupled binding and conformational change.</p> / Dissertation

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

The theory of non-orthogonal spin-adaptation for closed-shell molecular systems is presented, with an emphasis on application to the coupled cluster family of electronic structure methods. To aid in the derivation of efficient and compact working equations, a new diagrammatic interpretation of the Goldstone diagrams is derived which only requires a small number of the many distinct diagrams and which directly produces equations in a factored form in terms of “spin-summed” tensor elements. This diagrammatic interpretation is applied to coupled cluster methods with quadruple excitations (CCSDTQ), including coupled cluster with a perturbative correction for quadruple excitations (CCSDT(Q)) and to CCSDTQ gradients and properties. The advantages of the non-orthogonal spin-adaption with respect to simplification and factorization of the working equations and to efficient implementation are presented and discussed. Additionally, specific optimizations of the implementation for often-overlooked issues such as tensor transposition, disk access, and removal of redundant and/or unnecessary operations are detailed. The resulting algorithm is implemented for the CCSDTQ and CCSDT(Q) methods and compared to existing codes, where a one to two order-of-magnitude improvement in efficiency is observed. The new implementation is also used for calculations on several larger molecular systems to illustrate the scalability of the method. / text

The prostaglandins comprise a group of bioactive lipids generated from arachidonic acid by cyclooxygenases and cell type-specific prostaglandin and thromboxane synthases. Prostaglandins mediate local cell signaling interactions by activation of G-protein coupled prostanoid receptors. Because the prostaglandins and their receptors are active in all tissues, they have an extraordinarily broad spectrum of physiological and pathophysiological functions that have hampered the development of safe prostanoid-based medications. This situation has emphasized the importance of understanding the functional properties of the prostanoid receptors and developing selective ligands capable of being used in patient care.The aims of this project were to identify novel regulatory functions of endogenous EP and FP prostanoid receptors in cultured human cells. Our results show that activation of EP₂ receptors in human microglia and astrocytes led to increased secretion of BDNF, a growth factor that regulates the survival of neurons. In the same cell lines, FP receptors regulate the induction of TNF-&alpha; gene expression through a classic G_q-PKC pathway. In microglia these FP receptors also stimulate a novel signaling crosstalk mechanism involving the up-regulation of TCF transcriptional function by Raf kinases, which culminates in the expression of the angiogenic inducer Cyr61. FP receptors also regulate the induction of angiogenic immediate early genes in cultured ciliary muscle cells, which may constitute the early steps in a mechanism by which commercial FP agonists reduce intraocular pressure in glaucoma therapy.The up-regulation of BDNF through glial EP₂ receptors constitutes a mechanism by which elevated PGE₂ in the inflamed brain might elicit either healing processes in the brain or neuronal apoptosis. On the other hand, induction of TNF-&alpha; and Cyr61 by glial FP receptors may mediate neuroinflammation and may also contribute to glioma tumor growth. Stimulation of FP receptors in the ciliary muscle leads to the induction of immediate early genes capable of coordinating tissue remodeling processes that have been previously documented. The results of these studies suggest novel regulatory functions of the prostanoid receptors in the brain and eye. Furthermore, these findings provide insight on how the selective modulation of the EP₂ and FP receptors might be therapeutically advantageous.

No description available.

In this thesis, convergence of time averages near statistical attractors of continuous flows are investigated. A relation between statistical attractor and essential Ω-limit set is proved, and using this a general definition for statistical attractor is given. Sufficient conditions are given for an observable to admit a convergent time average along the orbits of the flow. The general results are applied to flows on a torus, and in particular to systems of coupled phase oscillators that admit attracting heteroclinic networks in their phase space. A particular heteroclinic network that we call heteroclinic ratchet is observed and analysed in detail. Heteroclinic ratchets give rise to a novel phenomenon, unidirectional desynchronization of oscillators (ratcheting). The results obtained about the convergence of time averages near statistical attractors implies that heteroclinic ratchets induce, besides its other interesting consequences, frequency synchronization without phase synchronization. Different coupling structures that can give rise to ratcheting of oscillators are also investigated.

Objectives: Discuss use of a linear incision for placement of a magnetically coupled bone anchored hearing implant. Methods: Case series. Results: Two patients underwent placement of magnetically coupled bone-anchored hearing implants (BAHI) through linear incisions. The first, a 40-year-old female with congenital single-sided deafness, previously had successful implantation of a percutaneous bone anchored hearing implant through a linear incision; unfortunately, she developed pain and intermittent drainage at her abutment site with time, resulting in a request for removal of her device. As an alternative to complete removal, we offered to replace the percutaneous implant with a magnetically coupled BAHI, employing the same linear incision previously. The second patient, a 53-year-old obese female with limited neck mobility and mixed hearing loss, underwent primary placement of a magnetically coupled BAHI through a linear incision. Limitations in neck mobility and patient body habitus precluded use of a traditional C-shaped incision. Both patients underwent surgery successfully, healed without incident, had their devices activated 6 weeks after their procedures, and are able to wear their implants more than 8 hours per day without discomfort. Conclusion: Surgical techniques for bone-anchored implants continue to evolve. Though manufacturers of magnetically coupled devices recommend using C-shaped incisions with large skin flaps, our first reported cases suggest that a small linear incision immediately overlying the implant magnet may be an acceptable alternative. Potential benefits include a smaller incision, less hair removal, smaller flap, decreased surgical time, and less postoperative pain.

Inductively Coupled Plasma (ICP) facilities create high enthalpy ows to recreate atmospheric entry conditions. Although no condition has been duplicated exactly in a ground test facility, it is important to characterize the condition to understand how close a facility can come to doing so. An ICP facility was constructed at the University of Vermont for aerospace material testing in 2010. The current setup can operate using air, carbon dioxide, nitrogen, and argon to test samples in a chamber. In this work we investigate di erent ways to increase measured heat ux and expand our facility to operate supersonically. To do so, a water cooled injection system was designed to overcome failure points of the prior system. An investigation of heat ux methods that provide a baseline for the facility were also examined and tested. A nozzle con guration was also developed with an overall goal of increasing the plasma ow to reach sonic and supersonic velocities, allowing it to be compared with the existing subsonic system. An iterative approach was taken to develop a nozzle design that is robust enough to handle the harsh environment, yet adaptable to the pre-existing facility components. The current design uses interchangeable sonic and supersonic nozzles which also allow for appropriate plasma gas expansion. Data are taken through retractable and goose-neck probe sample holders during testing. Heat ux can be determined by use of a Gardon gage, slug calorimeter, and water cooled calorimeter. Total and static pressure are determined from a pitot tube and pressure tap, which are then manipulated into a velocity measurement. A comparison between subsonic and supersonic operation is then made with these data. Existing literature uses correlations between jet diameter and velocity gradients to determine the e ective heat ux. This investigation found that the experimental and theoretical heat ux results scale correctly according to the correlations.