The human body is a well tuned mechanism where systems work in synergy to provide a healthy quality of life. The human circulatory system transports oxygenated blood from the heart to the rest of the body delivering the proper nutrients for cells to function. When the heart malfunctions, serious complications can arise leading to sudden cardiac arrest. Congestive heart failure (CHF) is one heart disease that affects the synchrony of the heart’s ventricles. Cardiac resynchronization therapy (CRT) has been widely accepted as a treatment for CHF. Similar to traditional dual chamber pacing techniques, CRT adds a pacing lead to stimulate the left ventricle. Left ventricular leads are implanted via the coronary sinus which provides the easiest surgical access to the left ventricle. Another option for LV pacing is by using an epicardial lead. This option has proven to be safe and effective but requires major surgery. An epicardial lead is usually implanted by performing a thoracotomy. Many studies have been done to show the benefits of bi-ventricular pacing, therefore developing new methods to gain LV access safely and reliable are highly desirable. The epicardial satellite pacemaker, or EPI pacemaker, is a component of a larger CRT system. This implantable cardiac system is composed of a master pacing unit with leads and a remote satellite pacing unit. The master unit is a traditional CRT device electrically coupled to the right side of the heart. It controls the right atrium and ventricle via transvenous leads anchored to the endocardium of the heart. The master device generates the pacing pulses to stimulate the right atrium and right ventricle and a communications module to transmit pacing commands to the epicardial satellite device. The epicardial satellite pacemaker is a leadless device mounted directly on the epicardium of the left ventricle. The epicardial pacemaker can be implanted using a thoracoscopic procedure during implant of the master unit. In special events, it can be implanted using prophylactic techniques during heart bypass surgery of other surgical procedures where access to the heart is available. Much work needs to be done to prove the technology. But current RF communication capabilities in today’s devices offer the groundbreaking path to develop a satellite LV pacing design.

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This study evaluated the usefulness of a psychophysical model as part of a new ANSI/HFES 100 standard for CRT flicker. A graph based flicker prediction method developed from Farrell, 1987 was evaluated. The Farrell model is based on phosphor persistence, screen luminance, display size, and viewing distance. The graph based method assumes a worse case scenario (i.e. a white display screen shown on a display with P4 phosphor). While the Farrell model requires photometric measurements to be taken using special equipment, the graph based method require a knowledge of the display size, viewing distance, screen luminance, and refresh rate. Ten participants viewed different display sizes from different eccentricities under different levels of illumination and luminance. In each condition the display's refresh rate was manipulated using the Method of Limits to determine the critical flicker frequency (CFF). An Analysis of Variance was used to detirmine significant effects on CFF. CFF increased with increasing luminance and display size. Adequate illumination significantly increased CFF. A viewing eccentricity of 30 degrees (measured horizontally from the center of the screen) produced the highest CFF values. Under the conditions of 30 degrees eccentricity and 250 to 500 lux illumination, observed 50% CFF threshold values exceeded the 90% CFF threshold values predicted by the graph based method. This study demonstates that when tested under the same conditions it was developed under, the Farrell method successfully predicts flicker perception; however, when tested under conditions representative of real world working conditions, the Farrell model fails to predict flicker perception. New parameters for the model are suggested.<INPUT TYPE="hidden" NAME="abstract" VALUE="This study evaluated the usefulness of a psychophysical model as part of a new ANSI/HFES 100 standard for CRT flicker. A graph based flicker prediction method developed from Farrell, 1987 was evaluated. The Farrell model is based on phosphor persistence, screen luminance, display size, and viewing distance. The graph based method assumes a worse case scenario (i.e. a white display screen shown on a display with P4 phosphor). While the Farrell model requires photometric measurements to be taken using special equipment, the graph based method require a knowledge of the display size, viewing distance, screen luminance, and refresh rate. Ten participants viewed different display sizes from different eccentricities under different levels of illumination and luminance. In each condition the display's refresh rate was manipulated using the Method of Limits to determine the critical flicker frequency (CFF). An Analysis of Variance was used to detirmine significant effects on CFF. CFF increased with increasing luminance and display size. Adequate illumination significantly increased CFF. A viewing eccentricity of 30 degrees (measured horizontally from the center of the screen) produced the highest CFF values. Under the conditions of 30 degrees eccentricity and 250 to 500 lux illumination, observed 50% CFF threshold values exceeded the 90% CFF threshold values predicted by the graph based method. This study demonstates that when tested under the same conditions it was developed under, the Farrell method successfully predicts flicker perception; however, when tested under conditions representative of real world working conditions, the Farrell model fails to predict flicker perception. New parameters for the model are suggested." / Master of Science

This thesis evaluates the ISO 9241 Part 7, Ergonomic requirements for office work with visual display terminals (VDTs) - Part 7: Requirements for display with reflections. The thesis involved two phases of effort that evaluated the photometric measurements required in the ISO standard in terms of subjective image quality judgments. In phase one, seven monitors were evaluated photometrically according to the ISO 9241-7 standard to determine whether they were Class I, II, or III. Additionally, glare filters were attached to monitors to see if they change the ISO classification of the monitor. The results of phase one indicated that positive polarity always yielded either Class I or Class II because the Large Source, Screen Image Luminance Ratio (LR BDS/FDS) and the Specular Reflection Luminance Ratio (LR BDS/BD) always passed. Conversely, negative polarity always produced Class II or Class III because the Small Source, Specular Reflection Luminance Ratio (LR BDS/BD) failed every time. Also, the AF 150 and HF 300 were the best filters for reducing glare on monitors. The BF 10 and AF 100 or AF 200 ,on the other hand, were the worst because they intensified screen reflections. In phase two, human image quality judgments were collected to determine if people rated Class I, II, or III monitor-filter combinations differently under different lighting and different screen polarity conditions. Specifically, phase two assessed the effects of seven monitor/add-on glare filter combinations, five ambient lighting conditions, and two screen polarities on subjective image quality ratings. Each participant provided subjective image quality judgments by viewing alphanumeric text on the CRT screens. Subjective scale values also were correlated with ISO classifications and two ISO metrics: screen image luminance ratio (Diffuse, 200 lux) and specular reflection image luminance ratio. The ANOVA findings indicated that specular glare significantly degrades image quality ratings more than diffuse glare. The author contends that this finding is the result of an experimental context effect. In other words, the specular glare was so influential on subjective ratings of image quality that subjects paid little or no attention to reductions in contrast from the diffuse lighting conditions. The correlation analysis showed that the specular reflection luminance ratio and the negative polarity classifications did index subjective quality ratings. Finally, this thesis establishes a human factors basis to justify the measurement requirements in the ISO 9241-7 standard. Specifically, the findings show that it underemphasizes the contribution of the specular reflection luminance ratio' and overemphasizes the contribution of the screen image luminance ratio to compliance classification calculations, because the procedure gives equal weight to both ratios. / Master of Science

Rare earth elements consist of 15 lanthanides, Y and Sc. They are currently very important materials in many industrial branches (metalurgy, pollishing). One of these options is the usage as the compound of phosphors in electronic devices (television and computer displays. Because of their manufacturing cost, options of recovery from waste electrical and electronic equipment (WEEE) are investigated. This thesis deals with compoud elements of phosphors from displays of type CRT (cathode ray tube) and plasma TV. The 37 samples of phosphors from different displays were taken and processed for study of the compoud elements. Phosphors were separated to 4 subgroups in accordance with the corresponding type of displays: black-and-white CRT television displays (CRT_CB), color CRT television displays (TV_B), color PC displays (PC_B) and monochromatic PC displays (PC_M). The study was carry out by multiple features analysis that combined the inductively coupled plasma mass spectrometry (ICP-MS), the inductively coupled plasma optical emission spectrometry (ICP-OES), the resistance furnace with infrared detector (RF-IF) and the atomic absorption spectrometry (AAS). Based on the results of this analysis, main elements and potentionally hazardous elements of phosphors subgroup were defined. Concentration of rare...

Pendant très longtemps, les traitements contre les cancers se sont basés sur la cytotoxicité des chimiothérapies, sur leur capacité à tuer directement les cellules malignes ou à induire leur senescence. Mais cette cytotoxicité accrue et non ciblée a également pour effet de tuer les cellules du système immunitaire du patient. Cependant, il a été montré que la radiothérapie, les anthracyclines ainsi que l’oxaliplatine étaient capables d’induire une apoptose décrite comme étant une mort cellulaire immunogène. De ce fait, les cellules tumorales mourantes agiront comme vaccin thérapeutique.La mort cellulaire immunogène se caractérise par trois grands marqueurs : un stress du réticulum endoplasmique pré-mortem qui va induire la translocation de la calréticuline de la lumière du réticulum endoplasmique vers la surface cellulaire, la libération d’ATP dans le milieu extracellulaire permettant le recrutement des cellules dendritiques et l’activation de l’inflammasome NLRP3 via le récepteur P2RX7, et enfin la libération de la protéine HMGB1 dans le milieu extracellulaire, qui va aller interagir avec TLR4 à la surface des cellules dendritiques pour stimuler leur fonction présentatrice d’antigène. La première partie de ce travail a consisté à comprendre les mécanismes moléculaires précis par lesquels l’ATP est sécrétée activement lors d’une mort cellulaire immunogène. En utilisant une combinaison de techniques impliquant des criblages pharmacologiques, des techniques de monitorage de la localisation intracellulaire de l’ATP entre autres, nous avons montré qu’après un traitement par les inducteurs de la mort immunogène, l’ATP était redistribué des lysosomes aux autolysosomes et que sa sécrétion requiert la protéine lysosomale LAMP1. Nous avons également montré qu’il existait d’autres voies de libération d’ATP telles que la voie de signalisation Rho, et également l’ouverture des hémicanaux pannexine 1 (PANX1). De façon surprenante, nous avons observé une implication de PANX1 dans la translocation de LAMP1 à la surface cellulaire. Ces résultats ont permis de comprendre un peu plus précisément les mécanismes de sécrétion d’ATP dans la mort cellulaire immunogène, mettant en évidence l’importance de l’exocytose lysosomale caspases dépendante et PANX1 dépendante.La seconde partie de ce travail s’est portée sur l’étude d’une autre caractéristique de la mort cellulaire immunogène, à savoir l’exposition de la calréticuline à la surface cellulaire. En partant du constat qu’après un traitement par la mitoxantrone, la calréticuline était relocalisée en périphérie à la fois dans les cellules humaines et les cellules de levure, il a été suggéré que la voie d’exposition de la calréticuline était conservée phylogénétiquement. Nous avons montré que les phéromones pouvaient agir comme inducteurs physiologiques de l’exposition de la calréticuline dans les cellules de levure. Un criblage d’ARN interférant et des analyses de transcriptome nous ont permis de montré que les chimiokines, en particulier CXCL8 chez l’humain (appelé également interleukine-8) et son orthologue Cxcl2 chez la souris étaient impliquées dans la translocation de la calréticuline à la surface cellulaire. En traitant les cellules cancéreuses par la mitoxantrone, nous observons une production de CXCL8 par les cellules cancéreuses humaines in vitro et de Cxcl2 par les cellules cancéreuses murines in vivo. Un « knockdown » des récepteurs pour CXCL8/Cxcl2 réduit de manière significative l’exposition de la calréticuline à la surface cellulaire. Ces résultats ont donc montré l’importance des chimiokines dans la voie d’exposition de la calréticuline.L’ensemble de ce travail a permis de comprendre plus en détails deux des trois grandes caractéristiques de la mort cellulaire immunogène. / Cytotoxic anti-neoplastic agents were considered for a long time to mediate their therapeutic effects via their capacity to directly kill malignant cells. Nevertheless, this high cytotoxicity is non-targeted and will eventually diminish immune cells. During the last years, it has been shown that radiotherapy and some anticancer agents, such as anthracyclines and oxaliplatin, can stimulate actively anti-tumor immune responses. In fact, they can induce an immunogenic type of apoptosis, which we termed immunogenic cell death (ICD). Thereby, dying cells can act as therapeutic vaccine against residual cancer cells that overcame the initial treatment.ICD is characterized by three major hallmarks: a pre-mortem stress of the endoplasmic reticulum (ER), which triggers the translocation of the ER chaperone protein called calreticulin (CRT) to the cell surface, the secretion of ATP from apoptotic cells, which acts as a signal for the recruitment of dendritic cells and for the activation of the NLRP3 inflammasome via its receptor P2RX7, and the release of HMGB1 into the extracellular space, allowing it to interact with TLR4 and thus stimulate the antigen-presenting functions of the DCs.The first part of my work focused on the precise molecular mechanisms by which ATP is actively secreted during ICD. Using a large panel of techniques, including chemical compounds screens and monitoring the subcellular localization of ATP, we showed that following treatment of various tumor cells with ICD inducers, ATP is redistributed from lysosomes to autolysosomes and the lysosomal protein LAMP1 is required for active ATP secretion. We also showed that Rho and pannexin 1 (PANX1) are indispensable for efficient ATP release in response to ICD inducers. Surprisingly, we observed an unexpected link between PANX1 and the exposure of LAMP1 at the cell surface. These results will help to understand the mechanisms necessary for ATP secretion during ICD.In the second part of this work we further studied the surface exposure of CRT during ICD. We observed that mitoxantrone (MTX), which belongs to the group of anthracyclines, can induce a peripheral relocalisation of CRT, both in human cells and yeast cells. In addition, we showed that pheromones can act as a physiological inducer of CRT translocation in yeast. Focused siRNA screening combined with transcriptome analyses revealed that human CXCL8 (also called interleukin-8) and its mouse ortholog Cxcl2 play an essential role in the translocation of CRT to the cell surface. Interestingly, MTX-treated human cancer cells displayed an elevated production of CXCL8 in vitro. These results were confirmed in vivo, with MTX treated murine tumors, which also displayed elevated Cxcl2 levels. The MTX-induced CRT exposure was significantly reduced when we performed a knockdown of CXCL8/Cxcl2 receptors. Altogether, these results showed the importance of chemokine signaling circuitries in immunogenic CRT exposure.This work allows for the detailed understanding of the mechanisms of ICD and might thus be useful for further targeted drug development.

Dentre as fases do ciclo de vida do Gerenciamento de Processos de Negócios (BPM - Business Process Management), a fase de diagnóstico de processos pode facilitar a mudança de modo a fundamentar futuros esforços de aumento de produtividade, padronização da execução do trabalho e criação de uma rotina de trabalho mais eficiente. Como técnica de diagnóstico, a ARA (Árvore da Realidade Atual) é mais ampla pois demonstra a visão geral da situação da empresa. A pergunta de pesquisa que se pretende responder com este trabalho é: como o diagnóstico da Árvore da Realidade Atual pode promover melhorias em uma Unidade de Pesquisa Clínica (UPC)? O objetivo é analisar o relacionamento entre a aplicação do diagnóstico da ARA e as melhorias realizadas em uma UPC. Para tanto, foi utilizado como método um estudo de caso em uma UPC que utilizou ARA como técnica de diagnóstico precursora da implementação de melhorias organizacionais. Nos resultados deste estudo é apresentado o diagnóstico da ARA em uma UPC e são descritas as melhorias que ocorreram na organização a partir da aplicação desta técnica. Além disso, são identificados quais fatores de sucesso do BPM contribuíram para a aplicação da ARA. Conclui-se que a utilização da ARA como técnica de diagnóstico, além de fornecer uma análise que contempla as necessidades reais da organização, pode ser relacionada com o sucesso da implementação de melhorias. Este estudo deve fornecer subsídios aos gestores de UPCs em relação à efetividade das práticas administrativas passíveis a serem adotadas, além de ser importante para pesquisadores que atuam com diagnóstico de processos e BPM ao apresentar a efetividade da utilização da ARA como técnica e relacionar as melhorias obtidas com os fatores críticos de BPM. / Among the phases of the Business Process Management (BPM) lifecycle, the process diagnostics phase can facilitate the change in order to support future efforts to increase productivity, standardize the execution of work and create a more efficient work routine. As a diagnostic technique, CRT (Current Reality Tree) is broader because it demonstrates the overall picture of the company\'s situation. The research question that intends to answer with this work is: how the diagnosis of the Current Reality Tree can promote improvements in a Clinical Research Unit (CRU)? The objective is to analyze the relationship between the application of CTR diagnosis and the improvements performed in a UPC. For that, a case study was used as a method in a UPC that used CRT as diagnostic tool for the implementation of organizational improvements. The results of this study present the diagnosis of CRT in a CRU and describe the improvements that occurred in the organization from the application of this technique. In addition, it is identified which BPM success factors contributed to the application of ARA. It is concluded that the use of ARA as a diagnostic technique, besides providing an analysis that considers the real needs of the organization, can be related to the success of the implementation of improvements. This study should provide support to UPC managers concerning to the effectiveness of the administrative practices that may be adopted, and it is important for researchers working with process and BPM diagnoses to introduce the effectiveness of the use of ARA as a technique and to relate the improvements obtained with the critical BPM factors.

Se donnant un mécanisme de branchement critique ou sous-critique, on définit une procédure d'élagage de l'arbre aléatoire continu de Lévy associé. Cette procédure d'élagage est définie en plaçant des marques sur l'arbre grâce à des techniques de serpent de Lévy. On démontre alors que le sous-arbre obtenu après élagage est encore un arbre aléatoire continu de Lévy. Ce résultat est démontré en utilisant une propriété de Markov spéciale et un problème de martingale pour les processus d'exploration. On construit ensuite, par couplage, une autre procédure d'élagage qui définit un processus de fragmentation sur l'arbre. On calcule la famille de mesures de dislocation associée à cette fragmentation. Dans un deuxième travail, on considère une diffusion aléatoire dans un milieu Lévy stable. On montre que le processus des temps locaux renormalisé et recentré au minimum de la vallée standard de hauteur log t, converge en loi vers une fonctionnelle de deux processus de Lévy conditionnés à rester positifs indépendants. Pour démontrer ce résultat, on montre que la loi de la vallée standard est proche de celle de deux processus de Lévy conditionnés à rester positifs concaténés en 0. On obtient également la loi limite du supremum du temps local renormalisé.

Cette thèse est consacrée à l'étude de certains processus aléatoires à valeurs dans les arbres continus. Nous définissons d'abord un cadre conceptuel pour cette étude, en construisant une topologie polonaise sur l'espace des R-arbres localement compacts, complets et munis d'une mesure borélienne localement finie. Cette topologie, dite de Gromov-Hausdorff-Prokhorov, permet alors la définition de processus de Markov à valeurs arbre. Nous donnons ensuite une nouvelle construction du processus d'élagage d'Abraham-Delmas-Voisin, qui est un exemple de processus qui prend ses valeurs dans les arbres de Lévy. Notre construction, qui dévoile une nouvelle structure généalogique des arbres de Lévy, est trajectorielle, et permet d'identifier explicitement les transitions du processus d'élagage. Nous appliquons cette description à l'étude de certains temps d'arrêt, comme le premier temps auquel le processus franchit une hauteur donnée. Nous décrivons le processus à cet instant grâce à une nouvelle décomposition de type spinal. Enfin, nous nous intéressons à la fragmentation d'Aldous-Pitman de l'arbre brownien d'Aldous. En particulier, nous étudions, à la suite d'Abraham et Delmas, l'effet de cette fragmentation sur les sous-arbres discrets de l'arbre brownien. Le nombre de coupures nécessaires avant d'isoler la racine, convenablement renormalisé, converge vers une variable aléatoire de Rayleigh ; nous donnons un théorème central limite qui précise les fluctuations autour de cette limite

Rapidly growing quantities of e-waste (WEEE) demand the increasing attention of environmental policy all over the world. Developing countries are particularly affected by recycling and disposal activities, which are deemed harmful to health and environment. Holistic or integrated approaches to WEEE policy are required. The paper discusses first recycling technologies for glass from cathode ray tubes (CRT) and printed circuit boards (PCBs) in Vietnam. Thereafter the German approach to WEEE policy is adjusted to allow for an integrated policy. This is then adapted to allow for the recycling of used monitors and computers. / Sự gia tăng một cách nhanh chóng số lượng các chất thải từ các thiết bị điện, điện tử (WEEE) đòi hỏi sự tăng cường chú ý tới các chính sách môi trường toàn cầu. Các nước đang phát triển bị tác động đặc biệt bởi các hoạt động tái chế, do nó ảnh hưởng xấu tới sức khỏe và môi trường. Các phương pháp tổ hợp và toàn diện đối với các chính sách quản lý chất thải điện tử (WEEE) là đòi hỏi cấp thiết. Trong bài báo này, trước hết phân tích đánh giá các công nghệ tái chế thủy tinh đèn hình (thủy tinh CRT) và bản mạch in điện tử (PCBs) ở Việt Nam. Tiếp theo là phương pháp tiếp cận các chính sách quản lý chất thải điện tử của Cộng hòa liên bang Đức được sử dụng để điều chỉnh cho thích hợp nhằm đưa ra giải pháp tổ hợp có thể thích ứng cho việc tái chế màn hình Tivi và máy tính hỏng, hết hạn sử dụng và thải bỏ ở Việt Nam.