Dissertations / Theses on the topic 'X ray unit'

Este proyecto de doctorado se centra en la evaluación de calidad de una unidad de rayos X para aplicaciones dosimétricas. Esta tesis describe todo el proyecto en tres secciones diferentes. La primera parte puede considerarse una introducción para presentar los conceptos e instrumentos utilizados para este trabajo. La base teórica del principio de funcionamiento de un tubo de rayos X se explica en el Capítulo 1. El Capítulo 2 muestra las magnitudes y el sistema de unidades de Protección Radiológica. Estos dos primeros capítulos representan los antecedentes teóricos de mi tesis. El Capítulo 3 muestra el laboratorio montado durante la primera parte de mi trabajo de doctorado. La unidad de irradiación y el laboratorio relacionado se pusieron a punto en el marco de una colaboración entre los Laboratorios Nacionales de Frascati del INFN (INFN - LNF), la Agencia Espacial Italiana (ASI) y el Consorzio di ricerca Hypatia. El aparato de rayos X funciona entre 40 y 120 kV con corrientes de hasta 5 mA. Se pueden implementar diferentes filtraciones de acuerdo con la calidad de haz deseada. Un banco mecánico permite colocar dispositivos y muestras a diferentes distancias del ánodo del tubo de rayos X. La segunda parte muestra los principales resultados obtenidos con diferentes experimentos y pruebas para calificar la salida de radiación del tubo de rayos X: • diseño y desarrollo de una cámara de ionización para medir la salida dependiente del tiempo de la unidad de rayos X (Capítulo 4); • determinación de la posición del foco del tubo de rayos X, que es un punto de referencia importante de la línea de irradiación (Capítulo 5); • verificación experimental de la calidad del haz a través de mediciones HVL (Espesor de semireducción - Half Value Layer) con la cámara de ionización para la elección de combinaciones adecuadas de kilovoltios-filtración para lograr calidades de radiación bien identificadas, según lo especificado por las Normas Internacionales relevantes (ISO 4037). Los haces de la serie de espectro estrecho (serie ISO 4037 N) se seleccionaron porque su distribución de energía aproximadamente monoenergética es muy adecuada para estudiar la respuesta de los dispositivos en función de la energía del fotón. La concordancia entre los valores ISO y los experimentales es excelente: la discrepancia es inferior a aproximadamente el 5% (Tabla 6-3, Capítulo 6). • estudio sobre la uniformidad del campo de rayos X (Capítulo 7), que es una tarea importante que debe cumplir el haz de rayos X, ya que es importante que todas las áreas de campo sean equivalentes y que la dosis impartida al dispositivo bajo prueba sea independiente de la posición en que se coloque. Se utilizaron dos técnicas de medición diferentes para verificar la uniformidad. La primera se basa en un detector pasivo, película Gafchromica, y la segunda emplea un detector de silicio que funciona en modo corriente. La variabilidad total del campo es aproximadamente del 11% dentro de una región central de 8 cm de radio (párrafo 7.4, Capítulo 7). • medición espectral de los haces de rayos X utilizando espectrómetros de fotones basados en semiconductores (detectores de silicio y de telurato de cadmio). Estas mediciones son básicas para verificar la forma del espectro continuo de radiación de frenado y las energías de punto final de las componentes espectrales, además de las mediciones de calidad de HVL (Capítulo 8). Los espectros confirman lo que se esperaba de las mediciones de HVL: utilizando las combinaciones de kilovoltios-filtración adecuadas (escritas en la Tabla 6-3) es posible lograr las calidades de radiación bien identificadas de la serie N, la serie estrecha de ISO 4037, útil como referencia de calibración La actividad de la última parte de mi tesis doctoral se centró en un innovador detector activo para dosimetría de cristalino (Capítulo 9). Durante los últimos años se ha puesto de manifiesto la necesidad de una reevaluación detallada de la radiosensibilidad del cristalino. Varios estudios epidemiológicos han destacado una mayor incidencia de cataratas que la prevista previamente. Por estas razones, la ICRP redujo el límite de exposición para los trabajadores de 150 mSv por año a 20 mSv en un año promedio durante períodos definidos de cinco años consecutivos, sin que en ningún año se excedan los 50 mSv (ICRP 2011). Por lo tanto, el gran interés en este tema es la evaluación esencial de la dosis ocupacional en cristalino y la protección del ojo. Gracias a la calificación física del tubo de rayos X bajo un punto de vista metrológico, fue posible utilizar esta instalación de irradiación como banco de pruebas para el desarrollo y pruebas de tipo (estudio sobre energía y respuesta angular) de un prototipo de un dosímetro de cristalino basado en semiconductores y desarrollado dentro del equipo de trabajo. Esta parte innovadora de mi trabajo de doctorado representa un estudio de I + D sobre la necesidad de dosimetría operativa.
This PhD project is focused on the qualification of an X-ray unit for dosimetrical applications. This thesis describes all the project in three different sections. The first part can be considered an introduction for depicting concepts and instruments used for this work. The theorical basis of the working principle of an X-ray tube is explained in Chapter 1. Chapter 2 shows the quantities and units system on Radiation Protection. These first two chapters represent the theoretical background of my thesis. Chapter 3 depicts the laboratory assembled during the first part of my PhD work. The irradiation unit and the related laboratory were set up in the framework of a collaboration between INFN - Frascati National Laboratories (INFN - LNF), the Italian Space Agency (ASI) and Consorzio di ricerca Hypatia. The X-ray apparatus operates from 40 to 120 kV with currents up to 5 mA. Different filtrations can be implemented according to the desired beam quality. A mechanical bench allows positioning devices and samples at different distances from the anode of the X-ray tube. The second part shows the main results obtained with different experiments and tests to qualify the radiation output of the X-ray tube: • design and development of a monitor ion-chamber to measure the time-dependant output of the X-ray unit (Chapter 4); • determination the X-ray tube focus position, which is an important reference point of the irradiation line (Chapter 5); • experimental verification of the beam quality through HVL (Half Value Layer) measurements with ion-chamber for the best choice of adequate kilovolt-filtration combinations in order to achieve well-identified radiation qualities, as specified by relevant International Standards (ISO 4037). The beams from the narrow spectrum series (ISO 4037 N-series) were selected because their roughly mono-energetic energy distribution is well suited to study the response of devices as a function of the photon energy. The accordance between ISO values and experimental ones is excellent: the discrepancy is less than about 5% (Table 6-3, Chapter 6) . • study on the X-ray field uniformity (Chapter 7), which is an important task that the X-ray beam must comply with, because it is important that all the field areas are equivalent and wherever the device under test is placed, it is exposed to the same dose. Two different measurements techniques were involved to verify the uniformity. The first is based on a passive detector, Gafchromic film, and the second employs a silicon detector operating in current mode. The total field variability is about 11% within a central region of 8 cm radius (paragraph 7.4, Chapter 7). • spectral measurement of the X-ray beams using semiconductor-based photon spectrometers (Silicon and Cadmium-Telluride detector). These measurements lead a role for checking the continuum shape of bremsstrahlung spectrum and the endpoint energies of the spectral components in addition to the quality measurements of HVLs (Chapter 8). The spectra confirm what expected from HVL measurements: using the proper kilovolt-filtration combinations (written in the Table 6-3) is possible to achieve the well-identified radiation qualities of the N-series, the narrow series of ISO 4037, useful as calibrating reference. The activity for the last part of my PhD thesis was focused on an innovative active detector for eye-lens dosimetry (Chapter 9). During the last years the need of a detailed re-evaluation of the eye lens radio-sensitivity was put in evidence. Various epidemiological studies highlighted a higher incidence of cataracts than previously foreseen. For these reasons the ICRP reduced the exposure limit for workers from 150 mSv per year to 20 mSv in a year averaged over defined periods of five consecutive years, with no single year exceeding 50 mSv (ICRP 2011). Therefore, the keen interest on this topic is for the essential evaluation of the occupational eye dose and eye protection. Thanks to the physical qualification of the X-ray tube under a metrological point of view, it was possible to use this irradiation facility as test bench for the development and type testing (study on energy and angular response) of a semiconductor-based prototype of an eye-lens dosimeter developed within the work team. This innovative part of my PhD work represents a R&D study on a need for operational dosimetry.

Cette thèse est consacrée au développement d'un modèle End-to-End pour le spectrocalorimètre X-IFU qui observera à partir de 2028 l'Univers en rayons X avec une précision jamais atteinte auparavant. Ce travail s'est essentiellement organisé en deux parties. J'ai dans un premier temps étudié la dynamique des parties les plus internes des binaires X de faible masse à l'aide de deux sondes particulières que sont les sursauts X et les oscillations quasi-périodiques au kHz (kHz QPOs). En me basant sur les données d'archive du satellite Rossi X-ray Timing Explorer et sur des méthodes d'analyse spécifiquement développées dans ce but, j'ai notamment pu mettre en évidence pour la première fois une réaction du premier sur le second, confirmant le lien très étroit entre ces oscillations et les parties les plus internes du système. Le temps de rétablissement du système suite aux sursauts entre également en conflit dans la plupart des cas avec l'augmentation supposée du taux d'accrétion suite à ces explosions. Au travers d'une analyse spectro-temporelle complète des deux kHz QPOs de 4U 1728-34, j'ai également pu confirmer l'incompatibilité des spectres de retard des deux QPOs qui suggère une origine différente de ces deux oscillations. L'étude de leurs spectres de covariance, obtenus pour la première fois dans cette thèse, a quant à elle mis en évidence le rôle central de la couche de Comptonisation et potentiellement celui d'une zone particulièrement compacte de la couche limite pour l'émission des QPOs. Dans le second volet de ma thèse, j'ai développé un simulateur End-to-End pour l'instrument X-IFU permettant de représenter l'ensemble du processus menant à une observation scientifique en rayons X, de l'émission des photons par une source jusqu'à leur mesure finale à bord du satellite. J'ai notamment mis en place des outils permettant la comparaison précise de plusieurs matrices de détecteurs en prenant en compte les effets de la reconstruction du signal brut issu des électroniques de lecture. Cette étude a mis en évidence l'intérêt de configurations hybrides, contenant une sous-matrice de petits pixels capables d'améliorer par un ordre de grandeur la capacité de comptage de l'instrument. Une solution alternative consisterait à défocaliser le miroir lors de l'observation de sources ponctuelles brillantes. Situées au coeur de la performance du X-IFU, j'ai également comparé de manière exhaustive différentes méthodes de reconstruction des signaux bruts issus des détecteurs X-IFU. Ceci a permis de montrer qu'à faible coût en termes de puissance de calcul embarquée, une amélioration significative de la résolution en énergie finale de l'instrument pouvait être obtenue à l'aide d'algorithmes plus sophistiqués. En tenant compte des contraintes de calibration, le candidat le plus prometteur apparaît aujourd'hui être l'analyse dans l'espace de résistance. En me servant de la caractérisation des performances des différents types de pixels, j'ai également mis en place une méthode de simulation rapide et modulable de l'ensemble de l'instrument permettant d'obtenir des observations synthétiques à long temps d'exposition de sources X très complexes, représentatives des futures capacités du X-IFU. Cet outil m'a notamment permis d'étudier la sensibilité de cet instrument aux effets de temps mort et de confusion, mais également d'estimer sa future capacité à distinguer différents régimes de turbulence dans les amas de galaxies et de mesurer leur profil d'abondance et de température. A plus long terme ce simulateur pourra servir à l'étude d'autres cas scientifiques, ainsi qu'à l'analyse d'effets à l'échelle de l'ensemble du plan de détection tels que la diaphonie entre pixels
This thesis is dedicated to the development of an End-ta-End model for the X-IFU spectrocalorimeter scheduled for launch in 2028 on board the Athena mission and which will observe the X-ray universe with unprecedented precision. This work has been mainly organized in two parts. I studied first the dynamics of the innermost parts of low mass X-ray binaries using two specific probes of the accretion flow: type I X-ray bursts and kHz quasi-periodic oscillations (kHz QPOs). Starting from the archivai data of the Rossi X-ray Timing Explorer mission and using specific data analysis techniques, I notably highlighted for the first time a reaction of the latter to the former, confirming the tight link between this oscillation and the inner parts of the system. The measured recovery time was also found in conflict with recent claims of an enhancement of the accretion rate following these thermonuclear explosions. From the exhaustive spectral timing analysis of both kHz QPOs in 4U 1728-34, I further confirmed the inconsistancy of their lag energy spectra, pointing towards a different origin for these two oscillations. The study of their covariance spectra, obtained here for the first time, has revealed the key role of the Comptonization layer, and potentially of a more compact part of it, in the emission of the QPOs. In the second part of my thesis, I focused on the development of an End-to-:End simulator for the X-IFU capable of depicting the full process leading to an X-ray observation, from the photon emission by the astrophysical source to their on-board detection. I notably implemented tools allowing the precise comparison of different potential pixel array configurations taking into account the effects of the event reconstruction from the raw data coming from the readout electronics. This study highlighted the advantage of using hybrid arrays containing a small pixel sub-array capable of improving by an order of magnitude the count rate capability of the instrument. An alternative solution would consist in defocusing the mirror during the observation of bright point sources. Being a key component of the overall X-IFU performance, I also thoroughly compared different reconstruction methods of the pixel raw signal. This showed that with a minimal impact on the required on-board processing power, a significant improvement of the final energy resolution could be obtained from more sophisticated reconstruction methods. Taking into account the calibration constraints, the most promising candidate currently appears to be the so-called "resistance space analysis". Taking advantage of the obtained performance characterization of the different foreseen pixel types, I also developed a fast and modular simulation method of the complete instrument providing representative synthetic observations with long exposure times of complex astrophysical sources suffinguish different turbulence regimes in galaxy clusters and to measure abundance and temperature profiles. In the longer run, this simulator will be useful for the study of other scientific cases as well as the analysis of instrumental effects at the full detection plane level such as pixel crosstalk

Recent improvements in deep learning architectures, combined with the strength of modern computing hardware such as graphics processing units, has lead to significant results in the field of image analysis. In this thesis work, locally connected architectures are employed to reduce noise in flash X-ray diffraction images. The layers in these architectures use convolutional kernels, but without shared weights. This combines the benefits of lower model memory footprint in convolutional networks with the higher model capacity of fully connected networks. Since the camera used to capture the diffraction images has pixelwise unique characteristics, and thus lacks equivariance, this compromise can be beneficial. The background images of this thesis work were generated with an active laser but without injected samples. Artificial diffraction patterns were then added to these background images allowing for training U-Net architectures to separate them. Architecture A achieved a performance of 0.187 on the test set, roughly translating to 35 fewer photon errors than a model similar to state of the art. After smoothing the photon errors this performance increased to 0.285, since the U-Net architectures managed to remove flares where state of the art could not. This could be taken as a proof of concept that locally connected networks are able to separate diffraction from background in flash X-Ray imaging.

Des découvertes inédites dans le domaine de l'astronomie en rayons X nécessitent une nouvelle génération d'instruments, pouvant observer le ciel en combinant des hautes résolutions spatiales et spectrales. Ce besoin constitue le fondement du X-ray Integral Field Unit (X-IFU) de la mission Athena de l'ESA, dont le lancement est prévu en 2031. La complexité de la chaîne de détection du X-IFU nécessite un suivi de ses perturbations instrumentales. Des simulations bout-à-bout, reproduisant les observations en rayons X de l'émission des photons d'une source représentative à leur détection, sont un outil de choix pour ces études. Dans la première partie de cette thèse, j'utilise ces simulateurs pour quantifier l'effet de la diaphonie entre les pixels, pour dériver une spécification sur la connaissance du bruit de fond instrumental, ou encore pour estimer la sensibilité spectrale de l'instrument. Mes résultats confirment que le X-IFU atteindra ses exigences en taux de comptage pour des sources étendues brillantes. Ils démontrent aussi qu'une bonne connaissance des raies spectrales, ainsi que du niveau bruit de fond instrumental (à mieux que 2%) est indispensable pour éviter des erreurs systématiques dans le traitement des données. L'analyse des performances doit cependant être couplée à des études de faisabilité des objectifs scientifiques du X-IFU. Cela concerne particulièrement les observations de sources étendues, qui feront appel à tout le potentiel de l'instrument. La deuxième partie de ce travail analyse les capacités du X-IFU à caractériser les propriétés physiques et chimiques du milieu intra-amas, ainsi que sa turbulence. Pour obtenir des simulations représentatives, des modèles ou d'autres simulations numériques sont utilisés comme point de départ de ces études. Mes résultats montrent la puissance du X-IFU à mesurer les propriétés des amas de galaxies, même à haut redshift (z ~ 2) et sur des temps d'exposition de 100ks. Je présente également une nouvelle façon d'aborder les biais sur les diagnostics spectraux. Elle permettra d'optimiser les observations de la turbulence dans les amas. Enfin, pour remplir ses objectifs scientifiques, le X-IFU nécessitera une calibration très précise. La troisième partie de cette thèse aborde différents points de la calibration du X-IFU, notamment la connaissance de son échelle de gain, de son efficacité quantique et de son bruit de fond instrumental. Je démontre que de nouvelles méthodes de correction de gain et de surveillance du niveau de bruit de fond instrumental sont nécessaires pour vérifier les spécifications attendues. Ces résultats permettent d'optimiser l'architecture de l'instrument (par ex., sources modulées de rayons X, stratégies de corrections) et de mieux préparer ses phases de calibration au sol et en vol. Les études de calibration se feront aussi et surtout par des essais en conditions représentatives, comme dans le banc cryogénique développé et caractérisé à l'IRAP au cours de ma thèse
Future breakthroughs in X-ray astronomy require a new generation of X-ray instruments, capable of observing the sky with high spectral and spatial resolutions combined. This need drives the development of the X-ray Integral Field Unit (X-IFU) onboard the future European X-ray observatory Athena scheduled for a launch in 2031. The complexity of the X-IFU and of its readout chain calls for a close monitoring of its instrumental effects. This can be investigated using dedicated end-to-end simulators, which reproduce an X-ray observation, from the emission of X-rays by an astrophysical source to their detection. In the first part of this thesis, I use this approach to quantify the impact of crosstalk between pixels, to derive the requirement on the reproducibility of the instrumental background, and to estimate the line sensitivity of the instrument. I demonstrate that the X-IFU will be capable of observing bright, extended sources with a required high-resolution throughput above 80%. I also show that an accurate knowledge of the spectral lines (their energy and their profile), as well as of the non-X-ray background level (to better than 2%) are needed to minimise systematic errors in the observation. Analysis of the instrumental effects need to be coupled with feasibility studies of the core science objectives of the X-IFU to verify the potential of the instrument. This is valid in particular for extended sources, which will use this integral field unit at its full capabilities. In the second part of this work, I investigate the ability of the X-IFU to characterise the properties of the intra-cluster medium and its turbulent motions. To guarantee a representative result, both toy models and hydrodynamical simulations of clusters are used as inputs of end-to-end simulations. My results underline the strengths of the X-IFU, which will provide an accurate view of the physics and the chemical enrichment of clusters, even at high redshift (z ~ 2) with typical 100ks exposure. I also put forward an analytical way to estimate the systematic errors on line diagnostics in turbulence-related studies, which will be of particular interest to optimise future observations. To fulfil its science objectives, the X-IFU will require a careful calibration. The third part of this thesis presents studies on this topic related to the energy scale, the instrumental background, or the quantum efficiency. I demonstrate that new methods of gain drift correction and background monitoring are required to meet the expected requirements. These results provide constraints on the design of the instrument (e.g., modulated X-ray sources, correction strategies) and can be used to plan ground or in-flight calibration activities. Calibration studies will also be performed experimentally, notably using the test bench developed and characterised at IRAP during my thesis

Master thesis deals with creating a new design of mobile x-ray machine. Three studies of design were created on the base of processed analysis, when the best one were chosen and developed as a final design. The final design takes into account all egonomics and technical requirements and creates a machine with less technical and more favorable view for patients. Simplification and better arranged the control panels bring easier service for operators.

Feldspars are one of the archetypical families of framework silicates. They not only comprise around 60% volumetrically of the Earthâ s crust, but are among some of the most structurally complicated minerals. Investigation into the structural behavior of various intermediate plagioclases at pressure has been undertaken with the intent of categorizing the elastic behavior with pressure across the solid solution series and establishing a conceptual model to characterize feldspar compression. Complex behavior has been observed in the Equation of State for plagioclase feldspars in excess of 3 GPa, including an anomalous softening of ordered albite in excess of 8.4 GPa (Benusa et al 2005: Am Min 90:1115-1120). This softening was not observed in the EoS for the more intermediate plagioclase compositions containing between 20 and 40 mol% of end-member anorthite. The calculated elastic compliance tensor sums at room pressure show a general stiffening with increasing anorthite component, small elastic changes at the C-1 to I-1 transition, and a dominantly first-order response at the P-1 to I-1 transition near end-member anorthite. The crystal structure of An37 plagioclase was determined by single-crystal X-ray diffraction. The compression mechanisms in An37 are similar to those in albite at lower pressures. The softening in albite at higher pressures is therefore attributed to the structural shearing in albite that is absent in An37 plagioclase up to 9.5 GPa.
Master of Science

The goal of master’s thesis is design of a three-axis manipulator working as x-ray unit. Axis include one rotary and two liner. The work is based on the existing manipulator and the goals are reducing vertical installation space, weight reduction, increasing accuracy and repeatability. Creating 3D model with computational report from available components. There is resulting variant solved with linear motor in this thesis with that there is indicated alternative variant but not dealt with in detail.

Introdução: A síndrome do desconforto respiratório agudo (SDRA) tem como parte do seu tratamento uma ventilação mecânica adequada. A manobra de recrutamento alveolar (MRA) faz parte de um grupo de estratégias empregadas nos quadros moderados e graves. A MRA consiste na aplicação de um aumento de pressão transitório e controlado nas vias aéreas no intuito de abrir alvéolos previamente colapsados. A Tomografia de Impedância Elétrica (TIE) é capaz de avaliar o potencial de recrutamento alveolar (PRA) a beira leito. Objetivos:1) Comparar o PRA calculado pela TIE (através do ganho de complacência regional) com a TC. 2) Avaliar o \"deslocamento vertical de volume\" como índice de recrutamento alveolar.3) Estimar precocemente o PRA, através das manobras de recrutamento de rastreio propostas, utilizando a TIE. Método: Avaliamos o PRA em um modelo experimental de SDRA. Utilizamos 15 suínos da raça Landrace. Os animais foram sedados e intubados, em seguida, submetidos ao modelo experimental de SDRA desenvolvido na Faculdade de Medicina da Universidade de São Paulo (LIM-09). Ao término da lesão, um grupo de 7 animais recebeu uma sequência randomizada de manobras de recrutamento de rastreio propostas (Pressões inspiratórias de 30, 35 e 40 cmH2O) seguidas da manobra de recrutamento máxima (Pressão inspiratória de 60 cmH2O). Os animais foram monitorados com TIE e Tomografia computadorizada por raio X (TC) durante todas as manobras de recrutamento. Outro grupo de 8 animais ,submetidos a mesma lesão e com medidas de TC e TIE, foi retirado do banco de dados do LIM-09 e também analisados. Utilizamos o programa IBM® SPSS® Statistics 9.0 e 20.0.Resultados:1) PRA calculado pela TIE atráves do ganho de complacência regional corrigido para hiperdistensão, comparado com TC, apresentou um R2=0,76. 2) PRA calculado pelo ganho de complacência regional corrigido para hiperdistensão combinado com o deslocamento vertical apresentou R2 = 0,91 comparado a TC .3) As manobras de rastreio não conseguiram predizer quantitativamente o PRA mas auxiliariam na correção da hiperdistensão. Conclusões: A TIE é capaz de avaliar o recrutamento alveolar a beira leito. O deslocamento vertical combinado com o ganho de complacência regional corrigida para hiperdistensão representam de forma semelhante a TC o comportamento pulmonar durante uma MRA. A aplicação de uma manobra de recrutamento de rastreio pode ser útil para uma manobra de recrutamento máxima mais segura
Introduction: The acute respiratory distress syndrome (ARDS) treatment demands a proper mechanical ventilation strategy. The alveolar recruitment maneuver (ARM) is an intervention applied in moderate and severe cases of ARDS. ARM is a transitory and controlled increase in mechanical ventilator pressure delivered to the lungs aiming to open previously collapsed alveoli. The electrical impedance tomography (EIT) is a valuable tool at bedside; it is able to monitor and to help during an ARM performance through the estimation of the alveolar recruitment potential (ARP). Objectives: 1) To compare the ARP with the EIT as a regional compliance improvement quantification adjusted for lung hyperdistention with CT. 2) To evaluate the \"volume vertical displacement\" at the same pressure as alveolar recruitment index using EIT and CT. 3) To estimate earlier the ARP using the EIT through a screening recruitment maneuver. Methods: We evaluated the ARP in an experimental model of ARDS. We studied 15 Landrace race pigs. Subjects were sedated, intubated and submitted to the ARDS experimental model developed at Medical investigation laboratory n ° 09, University of São Paulo. In the end of the lung injury, a group of 7 pigs received a randomized sequence of screening recruitment maneuvers (inspiratory pressures of 30, 35 and 40 cmH2O) followed by a maximum recruitment maneuver (inspiratory pressure of 60 cmH2O).EIT and x-ray computed tomography (CT) monitored the steps of each recruitment maneuver. Another group of 8 pigs, submitted to the same lesion and with measures of EIT and CT, were extracted from our data bank. Analysis was performed at IBM® SPSS® Statistics 20.0. Results: 1) ARP calculated by EIT (regional compliance improvement quantification) reached a R2=0,76 when compared to CT. 2) The combination of regional compliance improvement and volume vertical displacement obtained R2 = 0,91 when compared to CT 3) The screening recruitment maneuvers were not able to predict quantitatively the ARP, but they helped in the lung hyperdistension adjustment. Conclusions: EIT is able to evaluate the ARP at bedside. The combination of regional compliance improvement and volume vertical displacement give information similar to CT about the lung behavior during a ARM. The application of a recruitment screening maneuver might be useful for more safe ARM

Abstract Multifunctional enzyme type 2 (MFE-2) is a peroxisomal enzyme participating in the breakdown of fatty acids in eukaryotes. Depending on the organism, MFE-2 is composed of two to four functional units, out of which the two enzymatic ones, 2-enoyl-coenzyme A (CoA) hydratase 2 and (3R)-hydroxyacyl-CoA dehydrogenase, are found in the all MFE-2s. These units are responsible for the catalysis of the second and third steps of the peroxisomal β-oxidation of various CoA thioesters of fatty acids and fatty acyl derivatives. Their (R)-stereospecificity and ability to accept a broad range of fatty acid CoA esters as substrates, in addition to the fact that they do not share any sequence similarity with the classical mitochondrial counterparts, make the enzymatic units of MFE-2 structurally very interesting. In this study, the three-dimensional structures of the (3R)-hydroxyacyl-CoA dehydrogenase and 2-enoyl-CoA hydratase 2 units were solved by crystallographic methods. The crystal structure of the (3R)-hydroxyacyl-CoA dehydrogenase unit of rat MFE-2 reveals a dimeric enzyme with an α/β short-chain alcohol dehydrogenase/reductase (SDR) fold. A unique feature of (3R)-hydroxyacyl-CoA dehydrogenase, however, is the separate C-terminal domain, which completes the active site cavity of the adjacent monomer and extends the dimeric interactions. The 2-enoyl-CoA hydratase 2 unit is a dimer with a unique two-domain structure proposed to evolve via gene duplication. The fold consists of two side-by-side arranged repeats of the hot-dog fold motifs, thus being highly reminiscent of the tertiary structures of the (R)-specific 2-enoyl-CoA hydratase of the polyhydroxyalkanoate synthesis pathway and the β-hydroxydecanoyl thiol ester dehydrase of fatty acid synthesis type II, both from prokaryotic sources. The importance of the N-domain in the binding of bulky substrates was shown by the enzyme-product complex structure, which also indicates the active site. For the first time, it was shown that the eukaryotic hydratase 2 uses an Asp/His catalytic dyad in catalysis. Moreover, a novel catalytic mechanism was proposed for (R)-specific hydration/dehydration. The solved structures also provide a molecular basis for understanding the effects of the patient mutations of MFE-2. They also allow disussion of the possible organisation of the three units in full-length MFE-2 of mammals.

Un nouveau modèle de biomembrane de type liposome a été développé à partir de lipides synthétisés comportant une unité biphényle sur leur chaînes sn2 et une chaîne aliphatique sn1 de longueur et insaturation variables. L'anisotropie de susceptibilité magnétique positive de ces molécules induit une déformation en oblate de ces liposomes dits " biphényles " dans le champ magnétique B0. Cette déformation spécifique a été caractérisée par RMN des solides 31P et 2H en faisant varier différents paramètres : l'intensité de B0, l'élasticité membranaire, la température et la taille des liposomes (Helfrich, 1973). Ces vésicules déformées ont pu être observées par microscopies optiques et électroniques et la rémanence de la déformation en dehors de B0 a pu être analysée par diffusion des rayons X aux petits angles (SAXS). Enfin, les premières applications des liposomes biphényles comme nouveau modèle de biomembrane pour analyser la structure et l'orientation (par RMN des solides 15N) de peptides ou protéines membranaires, ont été étudiées.

Abstract Lipids are necessary for living organisms and have various roles as, energy sources, hormone precursors and as components of membrane structures. Fatty acid β-oxidation is a pathway of energy metabolism, in which the fatty acyl-CoAs are degraded in several steps. Peroxisomal β-oxidation systems are found in all eukaryotes studied thus far, but the existence of a mitochondrial system is established in mammals only. Multifunctional enzyme type 2 (MFE-2) has been characterized from various species and is responsible for catalyzing the second and third steps in the R-specific peroxisomal β-oxidation pathway. MFE-2 accepts a wide range of substrates and displays great variation in domain organization and overall molecular mass. The crystal structures of individual domains of MFE-2 from several species have been determined previously. In this study, the structural knowledge of MFE-2 is further extended from the domain level to the assembly of the full-length enzyme. The crystal structure of Drosophila melanogaster MFE-2 (DmMFE-2) was solved at 2.15 Å resolution. The enzyme is a homodimer with 3R-hydroxyacyl-CoA dehydrogenase and 2E-enoyl-CoA hydratase 2 activities residing on each of the polypeptide subunits. Kinetic data combined with information from the structure, suggest that the catalytic domains of DmMFE-2 work as separate entities. It also appears that the enzyme does not assemble into dimers in vitro when the catalytic subunits are introduced in a solution as stand-alone proteins. The data were confirmed by two different methods, static light scattering and small-angle X-ray scattering. However, the primary use of SAXS was not to monitor the formation of dimers in solution, but instead it was used for structure determination of the human MFE-2. During the process, the structural information from DmMFE-2 was used as a scaffold for the human homolog. After collecting a wide range of SAXS data and numerous calculations, a plausible low resolution solution structure of human MFE-2 was obtained. The model reveals the overall assembly of the enzyme and the locations of the C-terminal SCP-2L domains (an unspecific lipid carrier), thus enabling further hypotheses regarding the possible role of the SCP-2L domain in the enzymatic reaction
Tiivistelmä Lipidit eli rasva-aineet ovat välttämättömiä eliöille ja niillä on lukemattomia rooleja mm. energianlähteinä, kalvojen rakenteina ja hormonien esiasteina. Rasvahappoja hajotetaan monivaiheisella metaboliareitillä, jota kutsutaan β-oksidaatioksi. Peroksisomaalinen rasvojen hajotusreitti on löydetty kaikista tähän asti tutkituista aitotumallisista, mutta mitokondrioissa tapahtuva rasvojen β-oksidaatio on löydetty vain nisäkkäiltä. Peroksisomaalinen monitoiminen entsyymi tyyppi 2 (MFE-2) katalysoi toisen ja kolmannen reaktion R-spesifisellä rasvahappojen hajotusreitillä ja se on karakterisoitu useilta eri lajeilta. MFE-2 muodostaa lajista riippuen hyvin erilaisia ja molekyylimassaltaan erikokoisia alayksikköyhdistelmiä, jotka pystyvät katalysoimaan erityyppisten substraattien hapetuksen. Eri lajien MFE-2:n yksittäisten alayksiköiden kiderakenteet ovat olleet tunnettuja jo vuosia. Tässä tutkimuksessa rakennetietämys laajenee MFE-2:n osalta alayksikkötasolta kokopitkän entsyymin tasolle, sillä banaanikärpäsen MFE-2:n (DmMFE-2) kiderakenne selvitettiin 2.15 ångströmin erotuskyvyllä. Tämä homodimeerinen entsyymi kantaa samassa polypeptidissä sekä 3R-hydroksiasyyli-KoA-dehydrogenaasi, että 2E-enoyyli-KoA-hydrataasi 2 -aktiivisuuksia. Kiderakenteen ja reaktiokinetiikan perusteella tehtiin johtopäätös, jonka mukaan DmMFE-2:n alayksiköt toimivat itsenäisinä kokonaisuuksinaan. Staattisen valonsironnan (SLS) ja röntgenpienkulmasirontamittauksien (SAXS) perusteella MFE-2:n erillisinä tuotetut alayksiköt eivät muodosta liuoksessa spontaanisti kokopitkän MFE-2:n kaltaisia oligomeerejä. Ihmisen MFE-2:n alhaisen erotuskyvyn malli määritettiin röntgenpienkulmasirontatekniikan avulla. Tässä prosessissa käytettiin hyväksi banaanikärpäsen entsyymin tarjoamaa rakennetietoa, jonka perusteella rakennettiin ensin runko ihmisen MFE-2:lle. Monivaiheisen prosessin jälkeen saatiin lopulta laskettua vakuuttava malli, joka paljastaa ensimmäistä kertaa ihmisen kokopitkän MFE-2:n rakenteen ja antaa mahdollisuuden tehdä alustavia johtopäätöksiä karboksiterminaalisen lipidejä epäspesifisesti sitovan alayksikön (SCP-2L) biologisesta roolista osana tätä monitoimista entsyymiä

La régulation de la transcription est un processus dynamique faisant intervenir le recrutement de complexes protéiques impliqués dans le remodelage de la chromatine. Parmi eux, mon travail s’est focalisé sur le complexe NuRD (Nucleosome Remodeling and histone Deacetylation) et sa sous-unité de liaison à l’ADN CpG MBD3. Pour cela une approche de biologie structurale intégrative combinant la préparation biochimique, la caractérisation biophysique et l’étude structurale par cryo-EM et cristallographie aux rayons-X a été mise en place. Les caractérisations biophysiques de MBD3 ont permis de mettre en évidence son interaction avec un ADN non-modifié CpG et des cristaux diffractant jusqu’à 3.9 Å ont été obtenu. De plus la région désordonnée en aval du domaine de liaison a été identifiée et son impact dans la formation de complexe caractérisé. Des cristaux pour les différentes constructions en complexe avec l’ADN ont été obtenus et sont actuellement optimisés. Enfin l’optimisation de la purification et la préparation du complexe, ont permis la visualisation du complexe NuRD et mettent en avant pour la première fois une organisation en domaines du complexe
Transcription regulation of chromatin is a very dynamic process regulated through the recruitment of chromatin-remodeling complexes. My work focuses on NuRD for Nucleosome remodeling and histones deacetylation complex a 1 MDa multi-subunit protein complex and its subunit MBD3 a CpG-binding protein and more precisely on an integrated biology approach of this molecular assembly and its interaction with DNA. It combines biochemical preparation, biophysical characterization, single particle cryo-eletron microscopy and x-ray crystallography. Biophysical analysis show that MBD domain of MBD3 interacts with unmodified CpG DNA, a crystal diffracting up to 3.9 Å were obtained. Moreover a C-terminal intrinsically disordered region of MBD3 were identified and despite is inherent disorder seems to increase the binding affinity of MBD3 for DNA. Crystals were obtained for both constructs in complex with DNA and are currently optimized.Cryo-EM study of NuRD complex allows us to develop and optimized purification and grids preparation for the visualization of the complex. The present results reveal a domain organization of the complex never identify before

Computer and Information Science
Ph.D.
Information fusion aims to develop intelligent approaches of integrating information from complementary sources, such that a more comprehensive basis is obtained for data analysis and knowledge discovery. Our Protein Biological Unit (ProtBuD) database is the first database that integrated the biological unit information from the Protein Data Bank (PDB), Protein Quaternary Server (PQS) and Protein Interfaces, Surfaces and Assemblies (PISA) server, and compared the three biological units side-by-side. The statistical analyses show that the inconsistency within these databases and between them is significant. In order to improve the inconsistency, we studied interfaces across different PDB entries in a protein family using an assumption that interfaces shared by different crystal forms are likely to be biologically relevant. A novel computational method is proposed to achieve this goal. First, redundant data were removed by clustering similar crystal structures, and a representative entry was used for each cluster. Then a modified k-d tree algorithm was applied to facilitate the computation of identifying interfaces from crystals. The interface similarity functions were derived from Gaussian distributions fit to the data. Hierarchical clustering was used to cluster interfaces to define the likely biological interfaces by the number of crystal forms in a cluster. Benchmark data sets were used to determine whether the existence or lack of existence of interfaces across multiple crystal forms can be used to predict whether a protein is an oligomer or not. The probability that a common interface is biological is given. An interface shared in two different crystal forms by divergent proteins is very likely to be biologically important. The interface data not only provide new interaction templates for computational modeling, but also provide more accurate data for training sets and testing sets in data-mining research to predict protein-protein interactions. In summary, we developed a framework which is based on databases where different biological unit information is integrated and new interface data are stored. In order for users from the biology community to use the data, a stand-alone software program, a web site with a user-friendly graphical interface, and a web service are provided.
Temple University--Theses

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Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Introdução: A tomografia de impedância elétrica (TIE) é uma técnica de imagem não invasiva que mensura o potencial elétrico na superfície torácica através de eletrodos colocados ao redor do tórax. Essas medidas são transformadas em uma imagem bidimensional da distribuição da impedância elétrica no tórax. Esse instrumento detecta modificações da densidade pulmonar e distribuição do volume corrente. Entretanto, é necessário melhor avaliação da sua eficiência em estimar o volume corrente (VT) a cada ciclo ventilatório. O objetivo do estudo é avaliar a correlação do volume estimado pela TIE com o VT aplicado durante o suporte ventilatório mecânico. Métodos: Inicialmente, foram estudados cinco suínos da raça Landrace. Os animais foram sedados, intubados e monitorados com a TIE. Foram aplicados volumes incrementais (100, 250, 500, 750 e 1000 mL) com a seringa de precisão em ZEEP e com PEEP de 5, 10 e 20 cmH2O, antes e depois da promoção de lesão pulmonar com lavagem com solução salina. Posteriormente, outros cinco animais foram monitorados com a tomografia computadorizada de tórax por raios X (TC) e a TIE. Foram aplicados volumes incrementais (250, 500 e 1000 mL) com a seringa de precisão em ZEEP e com PEEP de 10 e 20 cmH2O, também antes e depois da promoção de lesão pulmonar. A amplitude da variação de impedância mensurada pela TIE foi convertida em volume e foi calculado o volume de ar na TC. Análises de correlação e concordância foram realizadas com o programa \"R\" (© R Foundation for Statistical Computing). Resultados: Em ZEEP, o coeficiente de correlação entre os volumes estimado pela TIE e calculado pela TC foram, respectivamente, 0,90 e 0,96 na comparação com a seringa de precisão. O coeficiente de determinação entre a TIE e a seringa de precisão foi progressivamente reduzindo (0,90; 0,89 e 0,81 com PEEP de 5; 10 e 20, respectivamente) com o aumento do volume pulmonar promovido pela elevação da PEEP. A TC mostrou um deslocamento progressivo do conteúdo aéreo no sentido caudal com o aumento do volume pulmonar. Conclusões: Há uma boa correlação entre o volume estimado pela TIE e o VT aplicado durante o suporte ventilatório mecânico quando utilizados volumes e pressões usuais na prática clínica
Rationale: Electrical impedance tomography (EIT) is a noninvasive imaging tool that reconstructs a cross-sectional image of the lung\'s regional conductivity using electrodes placed circumferentially around the thorax. It is able to detect changes of lung air content and tidal volume (VT) distribution. However, better evaluation of its capacity to quantify VT variations is necessary. The aim of our study was to assess the correlation between volume estimated by EIT and tidal volume applied at different positive end-expiratory pressures (PEEP). Methods: Initially, in an experimental study five mechanically ventilated pigs monitored by EIT were studied. VT increments (100, 250, 500, 750 and 1000 mL) were applied with a calibrated syringe at zero end-expiratory pressure (ZEEP) and PEEP levels of 5, 10 and 20 cmH2O before and after lung-injury (induced by saline lavage). Another five pigs was monitored by EIT and x-ray computed tomography (CT). VT increments (250, 500 and 1000 mL) were applied with a calibrated syringe at zero end-expiratory pressure (ZEEP) and PEEP levels of 10 and 20 cmH2O before and after lung-injury. Lung air volume was calculated at CT scan and the amplitude of impedance change measured by EIT was converted to volume (mL). Correlation and agreement analysis was performed at \"R\" program (© R Foundation for Statistical Computing). Results: At ZEEP, volume estimated by EIT and volume calculated at CT obtained r2 = 0.90 and 0.96 respectively, when compared to calibrated syringe. The coefficient of correlation between EIT and calibrated syringe impaired (0.90; 0.89 and 0.81 with PEEP of 5; 10 and 20, respectively) with increase of the lung volume due to increased PEEP. CT showed a progressive displacement of the air content to the caudal thoracic levels with the increase of the lung volume. Conclusion: EIT is able to estimate tidal volume during mechanical ventilatory support when used volumes and pressures usually applied at bedside

Apesar da utilização da ventilação mecânica protetora como estratégia para o tratamento da síndrome do desconforto respiratório agudo, ao menos um quarto dos pacientes com essa síndrome ainda apresentam redução na função pulmonar após 6 meses de seguimento. Não se sabe se esta redução está relacionada com a gravidade da síndrome ou associada com a forma de ventilar o paciente. Nosso objetivo neste trabalho foi avaliar a associação entre alterações funcionais e estruturais do pulmão com parâmetros de gravidade clínica e de ventilação mecânica. Foi realizada uma análise secundária dos dados obtidos em estudo randomizado e controlado que incluiu pacientes com síndrome do desconforto respiratório agudo moderada/grave, internados em seis unidades de terapia intensiva em um hospital terciário da cidade de São Paulo. Foram analisados dados de pacientes que tinham ao menos um teste de função pulmonar no seguimento. O teste funcional incluiu a medida da capacidade vital forçada, volumes pulmonares e a capacidade de difusão do monóxido de carbono após 1, 2 e 6 meses de seguimento. Foram considerados variáveis independentes o volume corrente, a pressão de distensão e a pressão positiva ao final da expiração (todos medidos após 24 horas da randomização) e um sistema de classificação de prognóstico (APACHE II), a relação PaO2/FIO2 e a complacência respiratória estática (todos medidos antes da randomização). Também foi realizada tomografia de alta resolução do tórax juntamente com os testes de função pulmonar, e posterior análise quantitativa das imagens. Na avaliação de 6 meses também foi realizado teste de caminhada de 6 minutos e um questionário de qualidade de vida (SF-36). Um total de 21 pacientes realizaram o teste de função pulmonar após 1 mês e 15 pacientes realizaram após 2 e 6 meses de seguimento. A capacidade vital forçada foi relacionada inversamente com a pressão de distensão na avaliação de 1, 2 e 6 meses (p < 0,01). A capacidade de difusão do monóxido de carbono relacionou-se inversamente com a pressão de distensão e com o APACHE II (ambos p < 0,01) na avaliação de 1 e 2 meses. Após 6 meses de seguimento, houve correlação inversa entre a pressão de distensão e a capacidade vital forçada independente do volume corrente, da pressão de platô e da complacência estática respiratória após ajustes (R2 = 0,51, p = 0,02). A pressão de distensão também se relacionou com o volume pulmonar total, a densidade pulmonar media e a porcentagem de volume pulmonar não aerado ou pobremente aerado medidos através da análise quantitativa da tomografia computadorizada de tórax realizada na avaliação de 6 meses. Também foi observada relação entre a qualidade de vida após 6 meses de seguimento e a pressão de distensão considerando o domínio estado geral de saúde. Nós concluímos que mesmo em pacientes ventilados com reduzido volume corrente e pressão de platô limitada, maiores valores de pressão de distensão relacionaram-se com menores valores de função pulmonar no seguimento de longo prazo
Even after lung-protective ventilation had become the standard of care for acute respiratory distress syndrome, about 25% of moderate/severe acute respiratory distress syndrome patients present reduction in lung function at 6 months of follow-up. It is not known whether this reduction is related to the severity of acute respiratory distress syndrome or associated with mechanical ventilation strategy. Our aim was to evaluate the association between the functional impairment and mechanical ventilation. We performed a secondary analysis of data from a randomized controlled trial in acute respiratory distress syndrome that included patients with moderate/severe acute respiratory distress syndrome in six intensive care units at an academic tertiary hospital. Were analyzed data from patients who had at least one pulmonary function test at the follow-up. A pulmonary function test that included forced vital capacity, lung volumes and carbon monoxide diffusion capacity was performed at one, two and six months of follow-up. We considered as independent risk factors tidal volume, driving pressure and positive end expiratory pressure (all measured 24 hours after randomization), and a severity of disease classification system (APACHE II), the PaO2/FIO2 ratio and static respiratory compliance (all measured before randomization). We performed also a high-resolution computed tomography of the lungs in the same time of the pulmonary function test if it was possible with a quantitative analysis. At 6 months after acute respiratory distress syndrome, a six minute walk test and a quality of life questionnaire (short form-36 questionnaire) were performed. A total of 21 patients performed the test after one month and 15 patients performed after 2 and 6 months follow-up. At one, two and six months, forced vital capacity was related to driving pressure (p < 0.01). Carbon monoxide diffusion capacity was related to driving pressure (p < 0.01) and to APACHE II (p < 0.01) at one and two months. At six months of follow-up driving pressure was associated with lower FVC independently of tidal volume, plateau pressure and baseline static respiratory compliance after adjustments (r2 = 0.51, p = 0.02). Driving pressure was related with total lung volume, mean lung density and percentage of non or poorly aerated compartments in total lung volume measured by quantitative analysis of computed tomography at 6 months. Driving pressure was also related to quality of life at 6 months of follow-up. Despite using a lung-protective ventilation strategy, after 6 months we still observed lung function impairment and driving pressure was the only ventilation parameter correlated with pulmonary function changes. We concluded that even in patients ventilated with low tidal volume, greater driving pressure was associated with worse long-term pulmonary function

O objetivo da Estratégia de Recrutamento Máximo (ERM) guiada pela TC de tórax é minimizar a quantidade de colapso alveolar e os mecanismos de lesão induzida pela ventilação mecânica (VILI). Os objetivos deste trabalho são comparar por meio da análise quantitativa das imagens obtidas pela TC durante ERM, em pacientes com SDRA, os seguintes parâmetros: colapso, hiperdistensão Tidal Recruitment (TR), Tidal Stretch (TS) e a distribuição de ar nos pulmões Métodos - Doze pacientes foram transportados para a sala de TC e seqüências de imagens foram obtidas durante a pausa expiratória e inspiratória ao longo da ERM. A ERM consistiu em ventilação modo Pressão Controlada com diferencial fixo de pressão 15 cmH2O e elevações progressivas da PEEP de 10 - 45 cmH2O (fase de recrutamento) e titulação da PEEP (25 - 10 cmH2O) FR=10 - 15 irpm, relação I:E 1:1 e FiO2 1.0. Os pulmões foram divididos em quatro regiões de acordo com o eixo esterno - vertebral (1 anterior e 4 posterior) Resultados - A idade media da população estudada foi de 46 ± 20,5 anos e cerca de 92% dos pacientes tinham SDRA de origem primária. Com o objetivo de manter o recrutamento alcançado pela ERM foram necessários níveis elevados de PEEP média de 23,7 ± 2,3 cmH2O. A relação PaO2/FiO2 aumentou de 131,6 ± 37,6 para 335,9±58,7 (p<0,01) após a titulação da PEEP. A quantidade de colapso global diminuiu de 54 ± 8% (P10pré) para 4,8 ± 6% (P45) (p<0,01), e em P25pós foi mantido em níveis baixos 6,7 ± 6% (p=1,0). Em relação ao TR global, diminuiu de P10pre (4 ± 4%) para P45 (1 ± 1%) (p=0,029), e também foi mantido em níveis baixos após a titulação da PEEP em P25pós (p=1,0). Quanto à hiperdistensão, houve aumento estatisticamente significativo entre P10pré e P45 (p=0,032), embora em termos absolutos este aumento foi inferior a 5%. A comparação entre P25pré e P25pós revelou que não houve diferença entre eles (p=1,0). Não houve aumento do Tidal Hyperinflation entre P10pré e P45 (p=0,95). O Tidal Stretch também diminuiu durante a ERM e foi mantido em níveis baixos em P25pós, semelhantes aos observados em P45. Em P10pre durante pausa expiratória, quase 80% do ar se localizava distribuído na metade anterior dos pulmões. Durante ERM a distribuição de ar foi progressivamente em direção à metade posterior, até que em P25pós atingiu quase 40% (p<0,01). Discussão - A análise tomográfica detalhada destes 12 pacientes portadores de SDRA apresentou como principais resultados que a Estratégia de Recrutamento Máximo guiada por TC de tórax reduziu de forma significativa a quantidade de colapso pulmonar global, de Tidal Recruitment, de Tidal Stretch sem, no entanto, intensificar significativamente a geração de hiperdistensão. Foram necessários níveis elevados de PEEP (cerca de 25 cmH2O em média) para a manutenção do recrutamento adquirido e para garantir distribuição mais homogênea do ar nos pulmões. A elevação da PEEP de 10 cmH2O pra 20 cmH2O, sem a realização de manobra de recrutamento, pode exacerbar os mecanismos de VILI ao invés de diminuí-los. A ERM não promove aumento relevante da hiperdistensão, frente à imensa contribuição na redução do colapso e dos outros mecanismos de VILI. Conclusões - A ERM e titulação da PEEP guiados pela TC de tórax diminuiu significativamente a quantidade de colapso pulmonar, Tidal Recruitment e Tidal Stretch, sem no entanto, aumentar significativamente a hiperdistensão. A ERM também promoveu distribuição de ar mais homogênea no parênquima pulmonar.
The goal of Maximal Recruitment Strategy (MRS) guided by thoracic CT scan is to minimize alveolar collapse and the mechanisms of ventilator induced lung injury (VILI). The objectives of this study were to compare by quantitative analyzes of CT scan image of the lungs obtained during MRS of patients with ARDS, the following parameters: collapse, overdistension, Tidal Recruitment (TR), Tidal Stretch (TS) and the gas distribution throughout the lungs. Methods - Twelve patients were transported to the CT room and sequences of CT scan at expiratory and inspiratory pauses were performed during MRS. MRS consisted of 2 min steps of tidal ventilation with fixed deltaPCV=15 cmH2O and progressive increments in PEEP levels (recruitment 10 - 45 cmH2O) and PEEP titration (25 - 10 cmH2O). RR=10 - 15 bpm, I:E ratio 1:1, and FiO2 1.0. The lungs were divided in 4 regions according to the sternum-vertebral axis (1 anterior and 4 posterior). Results - The mean age of the studied population was 46 ± 20,5 y.o., and 92% of the patients ad primary ARDS. In order to sustain recruitment obtained by MRS, mean PEEP levels of 23,7 ± 2,3 cmH2O were necessary and PaO2/FiO2 ratio increased from 131,6 ± 37,6 to 335,9±58,7 (p<0,01) after MRS and PEEP titration. Global collapse decreased from 54 ± 8% (P10pre) to 4,8 ± 6% (P45) (p<0,01), and was sustained at similar levels at P25post 6,7 ± 6% (p=1,0). Global TR also decreased from P10pre (4 ± 4%) to P45 (1 ± 1%) (p=0,029), and was sustained with the same levels at P25post (p=1,0). Regarding overdistension there was statistically significant increment from P10pre to P45 (p=0,032), although in absolute terms the increment was very low < 5%, and P25pre and P25post were identical (p=1,0). There was no increment of Tidal Hyperinflation from P10pre to P45 (p=0,95). TS also decrease during MRS and was maintained at low levels similar to P45 at titrated PEEP (P25post). At P10pre almost 80% of the air at FRC was located at anterior regions. During MRS the distribution of air was directed towards the posterior regions and at P25post was almost 40% (p<0,01). Discussion - The tomographic analysis revealed that during MRS there was a significantly reduction of pulmonary collapse, Tidal Recruitment and Tidal Stretch, without increasing significantly overdistension. High levels of PEEP were necessary to sustain recruitment obtained during MRS and homogeneous gas distribution throughout the lung parenchyma. When PEEP was increased from P10pre to P20pre there was an increment in TR and TS, without a significantly reduction in absolute mass of collapsed lung, suggesting that it may exacerbate the mechanisms of VILI. MRS does not promote relevant overdistention when balanced by its effects on reduction of the mechanisms of VILI. Conclusions - MRS and PEEP titration guided by CT scan decreased significantly lung collapse, Tidal Recruitment and Tidal Stretch, without increasing significantly overdistension. MRS also promoted a homogeneous gas distribution throughout the lung parenchyma.

No
Bulk crystallisation of protein therapeutic molecules towards their controlled drug delivery is of interest to the biopharmaceutical industry. The complexity of biotherapeutic molecules is likely to lead to complex material properties of crystals in the solid state and to complex transitions. This complexity is explored using batch crystallised lysozyme as a model. The effects of drying and milling on the solid-state transformations of lysozyme crystals were monitored using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), FT-Raman, and enzymatic assay. XRPD was used to characterise crystallinity and these data supported those of crystalline lysozyme which gave a distinctive DSC thermogram. The apparent denaturation temperature (Tm) of the amorphous lysozyme was ∼201 °C, while the Tm of the crystalline form was ∼187 °C. Raman spectra supported a more α-helix rich structure of crystalline lysozyme. This structure is consistent with reduced cooperative unit sizes compared to the amorphous lysozyme and is consistent with a reduction in the Tm of the crystalline form. Evidence was obtained that milling also induced denaturation in the solid-state, with the denatured lysozyme showing no thermal transition. The denaturation of the crystalline lysozyme occurred mainly through its amorphous form. Interestingly, the mechanical denaturation of lysozyme did not affect its biological activity on dissolution. Lysozyme crystals on drying did not become amorphous, while milling-time played a crucial role in the crystalline-amorphous-denatured transformations of lysozyme crystals. DSC is shown to be a key tool to monitor quantitatively these transformations.

Nine polycrystalline (Detector and Optical Grade) and Single Crystal CVD diamond detectors were characterised in terms of their defects and impurities with the specific aim to provide the much needed tool for selecting materials suitable for use in radiation detectors and in spectroscopy when exposed to alpha particles radiation or mammographic X-rays. The effectiveness of electron spin resonance (ESR), ultra-violet (UV) absorption, Raman broadening and thermo-luminescence (TL) emission as tools for performance evaluation were analyzed. The study has shown that defects (e.g. grain boundaries) and impurities (e.g. single substitution nitrogen concentration) played a role in the performance of CVD diamond wafers when used as dosimeter or spectrometer. In particular the observed higher values of single substitutional nitrogen concentrations, higher UV absorption and Raman broadening but lower TL emission values in the Optical Grade CVD diamond wafers were associated with their improved performance as detectors of alpha particles. The lower ESR, the lower UV absorption, higher TL emission values and lower Raman broadening were related to the better performance of both the Detector and Single Crystal CVD diamond wafers when used for alpha spectroscopy. An adopted and extended method developed for the correction of the ‘as accumulated’ spectra that takes into account the detector’s efficiency gave rise to an X-ray mammography spectrum that is independent of the detector type. This was used to justify the use the Monte Carlo simulated spectrum to evaluate the comparative responses of of iv pure diamond to that of the CVD diamonds wafers when exposed to simulated and actual X-ray exposures respectively. The research has provided an evaluation technique for selecting detectors suitable for different applications. The research furthermore, suggests that for the detection of X-ray photons, using a Detector Grade CVD diamond wafer is best suited for the task but generally the most consistent radiation detector material is the Single Crystal CVD wafer.

Thesis (M.S.)--State University of New York at Buffalo, 2007.
Title from PDF title page (viewed on Feb. 21, 2008) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Wobschall, Darold C. Includes bibliographical references.

碩士
中臺科技大學
醫療暨健康產業管理系碩士班
107
Aims: The purposes of this study are (1) understanding image quality; (2) using mammography screening benchmarks to recognize dissimilarities between mobile mammography units and fixed mammography units (3) analyzing the cost and the satisfaction in the two examine processes. Methods: Mammographic image data was used in 2014 to 2016, 5080 cases in fixed unit and 888 cases in mobile mammography unit. In order to review image quality, those sample image data were scored by three breast image experts with the double-blind. The satisfaction survey was conducted to investigate the implementation of mammography screening in 2018. There were 167 samples in the mobile mammography units, and 342 samples were in the fixed one. For the cost analysis, the activity-based costing analysis of the operation was carried out with the mobile mammography units in 2014 and 2016 and the mammography operation process in fixed mammography units. Result: After three breast expert scoring results, the mammogram quality was significantly different. Based on the result of the mammography screening benchmarks the fixed units much more better the mobile mammography units. Moreover, except tangible facets, both of the units without any significant difference on the result of the satisfaction survey. In the aspect of cost analysis results showed each mammographic examine in the fixed mammography units was NTD107.4 less than the mobile one. Conclusion: The running model of the mobile mammography units should be modifying in order to consist with the needs of people lived in Taiwan's remote areas. In the neighborhood hospital community, the examination should be directed to mammography medical institution for inspection, which can improve image quality, satisfaction and reduce costs. It is recommended to use a mobile mammography units’ vehicle to give a higher payment.

Indiana University-Purdue University Indianapolis (IUPUI)
Large protein molecules are abundant in biological cells but are very difficult to study in physiological conditions due to molecular disorder. For large proteins, most structural information is obtained in crystalline states which can be achieved in certain conditions at very low temperature. X-ray and neutron crystallography methods can then be used for determination of crystalline structures at atomic level. However, in solution at room or physiological temperatures such highly resolved descriptions cannot be obtained except in very few cases. Scattering methods that can be used to study this type of structures at room temperature include small-angle x-ray and neutron scattering. These methods are used here to study two distinct proteins that are both classified as glycoproteins, which are a large class of proteins with diverse biological functions. In this study, two specific plasma glycoproteins were used: Fibrinogen (340 kDa) and Alpha 1-Antitrypsin or A1AT (52 kDa). These proteins have been chosen based on the fact that they have a propensity to form very large molecular aggregates due to their tendency to polymerize. One goal of this project is to show that for such complex structures, a combination of scattering methods that include SAXS, SANS, and DLS can address important structural and interaction questions despite the fact that atomic resolution cannot be obtained as in crystallography. A1AT protein has been shown to have protective roles of lung cells against emphysema, while fibrinogen is a major factor in the blood clotting process. A systematic approach to study these proteins interactions with lipid membranes and other proteins, using contrast-matching small-angle neutron scattering (SANS), small angle x-ray scattering (SAXS) and dynamic light scattering (DLS), is presented here. A series of structural reference points for each protein in solution were determined by performing measurements under osmotic stress controlled by the addition of polyethylene glycol-1,500 MW (PEG 1500) in the samples. Osmotic pressure changes the free energy of the molecular mixture and has consequences on the structure and the interaction of molecular aggregates. In particular, the measured radius of gyration (Rg) for A1AT shows a sharp structural transition when the concentration of PEG 1500 is between 33 wt% and 36 wt%. Similarly, a significant structural change was observed for fibrinogen when the concentration of PEG 1500 was above 40 wt%. This analysis is applied to a study of A1AT interacting with lipid membranes and to a study of fibrinogen polymerization in the presence of the enzyme thrombin, which catalyzes the formation of blood clots. The experimental approach presented here and the applications to specific questions show that an appropriate combination of scattering methods can produce useful information on the behavior and the interactions of large protein systems in physiological conditions despite the lower resolution compared to crystallography.

Σκοπός της εργασίας αυτής είναι η χαρτογράφηση της δευτερογενούς ακτινοβολίας ακτινογραφικής λυχνίας μέσα στην αίθουσα εξέτασης, ενός συμβατικού ακτινολογικού μηχανήματος, συναρτήσει διαφόρων ακτινογραφικών παραμέτρων. Στόχος των μετρήσεων αυτών είναι ο υπολογισμός της σκεδαζόμενης ακτινοβολίας και της διαρρέουσας ακτινοβολίας σε διάφορες γωνίες από 0 μοίρες έως και 360 μοίρες, με βήμα 45 μοιρών, χρησιμοποιώντας έναν κυλινδρικό σκεδαστή νερού διαστάσεων: διάμετρος = 38 cm και ύψος 20 cm, σε διάφορες αποστάσεις από τον σκεδαστή (1.0 m, 1.5 m και 2.0 m), για διαφορετικό πάχος φίλτρου λυχνίας και διαφορετικά στοιχεία ακτινογράφησης.
Secondary radiation in classical radiography units in different angles (0-360 angles)and in different distances (1.0 m, 1.5 m and 2.0 m) around the X-Ray tube. The phnatom we use was cylindrical with water, the dimancional of the phantom was: d = 38 cm and h = 20 cm. Different thickness of tube filter and differnt kV,mA,mAs.