The Angiotensin II Type I Receptor (AT1R) is the main receptor that produces most of the physiological actions of the Renin Angiotensin System (RAS). Alterations of AT1R expression in renal and cardiovascular diseases make this receptor an attractive target for developing an imaging agent to monitor its expression in disease states. [18F]FPyKYNE-Losartan has been developed as a derivative of the clinically used AT1R blocker Losartan. The aim of this work was to characterize this tracer and evaluate its potential as an imaging agent for AT1Rs, thereby, progressing towards human imaging of the AT1R. MicroPET imaging in rats and PET imaging in pigs displayed specific AT1R binding, high kidney-to-blood and image contrast, and slow clearance from kidneys. [18F]FPyKYNE-Losartan was shown to have 2 types of labeled metabolites in rat plasma and kidneys: hydrophilic and hydrophobic, whereas, only hydrophilic metabolite(s) in pig plasma. Plasma protein binding of [18F]FPyKYNE-Losartan was determined, by an in vitro ultrafiltration method, to be 97% which is very similar to that of Losartan (98%). FPyKYNE-Losartan displayed full antagonism of Ang II pressor effect in rats in vivo, with an ED50 of 25.5 mg/Kg and 4-times (25%) less potency than Losartan. In vitro binding studies confirmed the binding selectivity of [18F]FPyKYNE-Losartan. Bmax and Kd parameters were determined to be 348 ± 112 fmol/mm2 and 49.4 nM, respectively. Rat dosimetry studies exhibited that the sex averaged effective doses of [18F]FPyKYNE-Losartan according to ICRP 60 and 103 protocols are 2.97E-02 (mSv/MBq) and 3.06E-02 (mSv/MBq), respectively, which are within an acceptable range compared with other F-18 labeled tracers and within the safety limits of the FDA. In conclusion, [18F]FPyKYNE-Losartan has an excellent potential for translation towards human imaging to monitor AT1R expression and guide therapy.

Realizamos neste trabalho a automatização da nova metodologia MHCalc, desenvolvida anteriormente em nosso laboratório, que teve como resultado o programa homônimo escrito em linguagem C para ambiente GNU/Linux, o qual avalia quantitativamente a seletividade de uma determinada proteína MHC. Esta avaliação quantitativa possibilita o estabelecimento de uma escala de preferência dos resíduos de ocorrência natural para cada uma das posições de interação da fenda de apresentação do MHC; por permutação destes resíduos, podem-se derivar regras de composição para peptídeos reconhecíveis em cada alelo estudado, inclusive na ausência de dados experimentais. A metodologia desenvolvida em nosso laboratório se baseia na avaliação da seletividade de cada bolsão independentemente, através da energia de interação do mesmo com cada aminoácido de ocorrência natural. O programa MHCalc utiliza o pacote de programas THORMM [Moret, 1998] de modelagem molecular para otimização geométrica das estruturas descritas, e tem como entrada unicamente um arquivo de coordenadas em formato POB contendo as coordenadas de um complexo MHC/peptídeo, tendo como saída uma tabela de dados contendo os resíduos de ocorrência natural em ordem de preferência para cada bolsão. Testamos o programa MHCalc para o complexo formado pela molécula HLA-DR1 (DRA DRB1 *01 01) e o peptídeo de Hemaglutinina, obtido no Brookhaven Protein Data Bank com a entrada 10LH, sendo este sistema escolhido por ser altamente estudado e com abundância de dados experimentais e teóricos para comparação de resultados. Até o presente momento obtivemos os dados referentes ao bolsão 1, os quais estão em pleno acordo com a literatura. / In this work we automated the new methodology MHCalc, developed previously in our laboratory, which resulted in the computational program with the same name, written in C language to GNU/Linux environment. The program MHCalc evaluates quantitatively the selectivity of a given MHC protein. This quantitative evaluation allows the establishment of a preference scale of the naturally occurring residues for each pocket of a MHC molecule. From such a study it may be derived composition rules to peptides recognizable in each allele studied, even in the absence of experimental data. The methodology developed in our laboratory is based on the selectivity evaluation of each pocket independently, through its interaction energy with each naturally occurring amino acid. The program MHCalc uses the molecular modeling package THORMM [Moret, 1998] to optimize the geometry of the structures described below, and needs as only entry the PDS like file with the coordinates of the MHC/peptide complex. The program finishes printing out a data file containing the naturally occurring residues in preference order for each pocket and the data used to order these residues. We tested the program MHCalc to the complex molecule HLA-DR1 (DRA DRB1 *01 01) with the Hemaglutinin peptide, obtained at the BrookHaven Prote in Data Bank (1 DLH entry). This system was chosen because it has been highly studied and so offers abundant experimental and theoretical data to compare our results. We obtained data referring to pocket 1 so far, which is in full agreement with the literature.

Coral reefs are one of the world’s most diverse yet heavily impacted marine ecosystems. As a result of many direct and indirect stressors, coral reefs have experienced major degradation over the last several decades. Declines in coral reefs in the Caribbean have been particularly acute and generally associated with the loss of key herbivores and an increase in algae. Herbivorous fishes such as parrotfishes can positively impact coral reefs by removing algae that compete with corals for light and space. However, many parrotfishes are also important coral predators. Predation on corals, known as corallivory, can adversely affect coral growth, reproduction and survivorship. In this time of changing environments and coral reef decline, understanding the context-dependent nature of parrotfish foraging behavior is of critical importance to scientists and managers. Knowledge of the responses of parrotfishes across a range of resource abundance will help scientists and managers better predict the impacts that these herbivores have on benthic communities as both herbivores and corallivores. In Chapter 1, we examined how six different species of coral reef herbivores (i.e. parrotfishes), all of which belong to a single feeding guild but represent a range of dietary specialization, respond to changes in the abundance of preferred food items. We conducted behavioral observations of parrotfishes in two regions of the Greater Caribbean, and compared consumption rates, diet preferences, and foraging territory size in relation to natural variation across sites in preferred resource abundance. We found that the more-specialized parrotfishes increased their dietary specialization, had smaller foraging territories, and increased their feeding rate with increased preferred resource abundance. In contrast, less-specialized species exhibited constant foraging traits regardless of the abundance of their preferred resources. This study suggests that differences in dietary preference, specialization, and subsequent nutritional demand may drive a differential response in foraging behavior by generalists and specialist herbivores to changes in resource abundance. Recognizing that generalists and specialists differ in the degree to which their foraging behaviors are context-dependent can allow researchers to better predict how herbivores shape the structure and function of marine and terrestrial ecosystems. In Chapter 2, we determined if and how corallivory rates and intensity by parrotfishes differ between two regions of the Greater Caribbean that vary in coral and parrotfish community composition and abundance. We found that more species of parrotfishes than previous studies suggest contribute to corallivory. However, corallivory rates and selectivity for coral species by parrotfishes were largely context-dependent, particularly with regards to the relative abundance of preferred corals and diversity of corallivores at a given site. Although we found that corallivory rates decrease with coral cover, it appears that areas of low coral cover may have high corallivory intensity and coral tissue loss, in part due to the relatively high abundance of corallivores in these areas. The impact of high corallivory intensity and tissue loss requires further knowledge regarding the fate of bite scars on corals.This information will help predict the positive and negative consequences of parrotfishes on coral persistence in the Caribbean. Evidence provided in this thesis furthers our understanding of the dual role of parrotfishes as herbivores and corallivores. Additionally, it reveals the implications of changing coral reef habitats on parrotfish behavior and subsequent coral reef health and resilience.

No description available.

L’objectif de cette thèse est d’étudier l’influence de l’architecture poreuse de zéolithes à porosité multimodale sur la sélectivité de catalyseurs dans l’hydrocraquage de charges lourdes, et aussi d’établir des relations prédictives propriétés/performances des matériaux catalytiques.Plusieurs séries de matériaux modèles possédant des réseaux mésoporeux secondaires différents ont été préparés par traitement alcalin de zéolithes de référence de type faujasite, par dessilication et par recristallisation en présence d’agent structurant organique. Les différentes méthodes de structuration de la mésoporosité ont été comparées et discutées en termes de rendements de synthèse des matériaux micro-mésoporeux, de volumes mésoporeux créés, de distribution de tailles des mésopores et de leur co-localisation avec les micropores. Des catalyseurs bifonctionnels ont ensuite été préparés par introduction d'une fonction hydrogénante/déshydrogénante, et utilisés pour l’hydroconversion du n-hexadecane et du squalane.L'activité des catalyseurs, exprimée par la vitesse de réaction à 230°C dans la conversion dun-hexadecane, et à 210°C dans celle du squalane, est linéairement corrélée au nombre de sites acides forts de la zéolithe.Quel que soit le mode de restructuration du réseau mésoporeux et l'architecture de celui-ci, une augmentation du volume mésoporeux conduit à un gain de sélectivité en isomères, produits primaires de réaction, et de symétrie de la distribution de produits de craquage. La sélectivité des catalyseurs, caractérisée par le rendement maximum en isomères, est gouvernée par le transfert de matière au sein des cristaux zéolithiques. Une corrélation directe entre le coefficient de diffusion effectif du n-hexane et la sélectivité des catalyseurs a été établie. / The objective of this thesis is to study the influence of the porous architecture of zeolites with multimodal porosity on the selectivity of catalysts in the hydrocracking of heavy feedstock and also to establish predictive relations between properties and performances of catalytic materials.Several series of model materials possessing different secondary mesoporous networks have been prepared by treating in alkaline medium faujasite reference zeolites either by desilication and or by recrystallization in the presence of an organic structuring agent. The different mesoporosity structuring methods were compared and discussed in terms of yields, created mesoporous volumes, mesopore size distribution and their co-localization with micropores. Bifunctional catalysts were then prepared by introducing a hydrogenating/dehydrogenating function and used for the hydroconversion of n-hexadecane and squalane.The activity of the catalysts, expressed as the reaction rate at 230°C in the conversion ofn-hexadecane and at 210°C in the case of squalane, is linearly correlated with the number of strong acid sites of the zeolite. Whatever the restructuring process of the mesoporous network and its architecture, an increase in the mesoporous volume leads to a higher selectivity into isomers, primary reaction products, and a higher symmetry of the distribution of cracking products. The selectivity of the catalysts, characterized by the maximum yield of isomers, is governed by the transfer of matter within the zeolite crystals. A direct correlation between the effective diffusion coefficient of n-hexane and the selectivity of the catalysts was established.

No description available.

L'amélioration de la vie des personnes en situation d'handicap est un défi majeur dans notre société. Dans le cas d'un handicap dû à des déficiences du système sensori-moteur, les solutions chirurgicales ou médicamenteuses peuvent rarement restaurer les fonctions altérées. Des solutions plus technologiques peuvent, dans certains cas, être utilisées afin de contourner les problématiques de dysfonctionnement du système nerveux. Une des solutions envisageables consiste à contrôler certaines fonctions par stimulation électrique fonctionnelle. Pour que cette stimulation soit efficace et se rapproche du contrôle naturel une approche intéressante consiste à utiliser les capteurs sensoriels naturels dans la boucle de contrôle du système. Dans le cadre de ce travail de thèse, nous nous intéressons aux systèmes d'acquisition électriques des signaux neurologiques provenant du système nerveux périphérique. L’idée est que les informations issues des fibres nerveuses afférentes obtenues à l’aide d’électrodes extra-neurales (ex. Cuff) pourraient permettre de « capter » l’information sensorielle provenant de plusieurs capteurs naturels sans être trop invasif.La principale difficulté de cette technique et de discriminer l'activité d'une fibre ou d’un groupe de fibres à partir du signal composite recueilli par l’électrode. Ce signal regroupe, en effet, l’information provenant d’un grand nombre de fibres afférentes et efférentes d’origine très différentes. Une des approches envisageables consiste à discriminer l’information des différentes fibres à partir de leurs caractéristiques physiologiques ou anatomiques. Les travaux présentés dans ce manuscrit cherchent à améliorer la sélectivité du recueil en fonction de la vitesse de propagation des différentes fibres. A noter qu’aucune solution réellement viable n’existe dans la littérature sur ce principe de sélectivité. Le premier objectif a donc été de prouver que dans un cas idéal (filtre parfait), il serait possible d’effectuer une discrimination efficace. Nos travaux sont basés sur des études temporelles, spatiales et spatio-temporelles afin d’évaluer les possibilités d'extraction de l'information utile à partir des potentiels extracellulaires simulés. Les simulations ont été effectuées à partir d'un modèle de système d'acquisition réaliste développé à partir des paramètres du modèle biophysiologique et du modèle d’électrode et du préamplificateur associé. Partant des résultats prometteurs obtenus dans un cas d’un filtre idéal, des implémentations de filtres IIR et FIR spatio-temporel du premier et second ordre ont été proposées. Les paramètres de stabilité des filtres proposés ont été étudiés et permettent d’envisager une implémentation physique efficace. / Improving the lives of people with disabilities is a major challenge in our society. In the case of a handicap due to deficiencies of the sensory-motor system, surgical or drug solutions can rarely restore the altered functions. More technological solutions may in some cases be used to bypass problematic malfunction of the nervous system. One solution is to control certain functions by functional electrical stimulation. For this to be effective stimulation and approaches the natural control an interesting approach is to use natural touch sensors in the system control loop. As part of this thesis, we focus on electrical systems acquisition neurological signals from the peripheral nervous system. The idea is that the information from the afferent nerve fibers obtained using extra-neural electrodes (eg. Cuff) could help to "capture" the sensory information from several sensors natural without being too invasive. The main difficulty of this technique and to discriminate the activity of a fiber or group of fibers from the composite signal received by the electrode. This signal includes, in fact, information from a large number of afferent and efferent very different origin. One possible approach is to discriminate the information of different fibers from their physiological and anatomical features. The work presented in this manuscript are looking to improve the selectivity of the collection based on the propagation speed of the different fibers. Note that no truly viable solution exists in the literature on this principle of selectivity. The first objective was therefore to prove that in an ideal case (ideal filter), it would be possible to make effective discrimination. Our work is based on studies of temporal, spatial and spatio-temporal order to assess the possibilities of extracting useful information from the simulated extracellular potentials. The simulations were performed from a realistic acquisition system model developed from the parameters of the model and biophysiological electrode model and associated preamplifier. Based on the promising results obtained in a case of an ideal filter, IIR filter implementations and spatiotemporal FIR of first and second order have been proposed. The proposed filter stability parameters have been studied and possible to envisage an effective physical implementation.

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxida-tive pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken to-gether, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elas-tase “super substrates” that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.

The influence of operation parameters on the drying of spherical porous particles containing a mixture of solvents evaporating into nitrogen in a continuously worked vibrated fluid-bed dryer was studied. A simulation based on the analytical solution to heat and mass transfer equations was applied and modifications were suggested.   Four different ternary liquid mixtures were selected: Acetone-Chloroform-Methanol (ACM), Ethanol- 2-propanol-Water (EIpW), Water-Ethanol-Ethyl Acetate (WEEa) and Ethanol-Methylethylketone- Toluene (EMekT). For the solid, physical properties of Pyrex was used.   Comparison of composition- and temperature- profiles indicated that there is no resistance against heat transfer within the solid and that the heat transfer is much faster than mass transfer.   Selectivity diagrams were drawn. The results indicated that selectivity is an important parameter in predicting the drying behavior.   The retention ratio was studied as performance parameter. Its variation was studied in response to changes in operation parameters, including gas velocity and temperature, as well as solid temperature and particle size.   A  modification  to  the  model  was  examined  by  assuming  a  liquid-content-dependent  diffusion resistance factor. It was observed that implementing such an assumption yields decreased values for retention ratios.   The  effect  of  vibration  on  heat  and  mass  transfer  coefficients  was  included  using  a  correlation suggested by Sbrodov and the resulting effect on retention ratio was examined. / Inverkan   av   driftparameter  på  torkning  av   sfäriska  porösa  partiklar  som   innehåller lösningsmedelblandningar som avdunstar i kväve i en kontinuerligt viberande fluidbädd-tork studerades.  En  simuleringsmodell  baserad  på  den  analytiska  lösningen  till  värme-  och materieöverföringsekvationerna användes och ändringar föreslogs.   Fyra  olika  tärnar  vätskeblandningar  valdes:  aceton-kloroform-metanol(ACM),  etanol-2- propanolvatten,(EIpW),     vatten-etanol-etylacetat     (WEEa)     och     etanol-metyletylketon- toluen(EMekT). För den fasta fasen användes fysikaliska egenskaper liknande Pyrex.   Sammansättnings-  och  temperatur-profiler  visade  att  det  inte  finns  något  motstånd  mot värmeöverföring  i  den  fasta  fasen  och  att  värmeöverföringen  sker  mycket  snabbare  än materieöverförningen.   Selektivitetsdiagram ritades. Resultaten indikerar att selektivititen är en viktig parmeter för att förutsäga beteendet vid torkning.   Retentionsförhållandet  användes  som  ett  prestandamått.  Dess  variation  med  avseende  på förändringar av  driftsparmetrar,  bland  annat  gasen  hastighet  och  temperatur  samt  den  fasta  fasens temperatur och partikelstorlek, studerades.   En modifiering av modellen undersöktes genom att införa en vätskehalts-beroende faktor för diffusionsmotståndet. Detta minskade värdena på retentionsförhållandena.   Vibrationens inverkan på värme- och materieöverföring infördes genom att använda Sbrodov samband, och den resulterande effekten på retentionsförhållandet observerades.

By the year 2030, 20% of the U.S. population will be 65 years of age or older. An increase in the demand for supportive health and social services is expected with the aging of the population. Demand for senior housing is expected to grow, too. This study explores what the social environment offers to lesbian, gay, bisexual and transgender (LGBT) seniors who relocated to LGBT retirement communities. Previous research asked LGBT seniors who did not live in LGBT senior housing about their housing preferences. The present study, for the first time, asked residents of existing LGBT senior living communities to explain why they chose to live in an LGBT retirement community. Focus groups were conducted at three retirement communities. Thirty-eight residents at the three study sites participated. Seven focus groups were conducted; each was audio recorded and transcribed verbatim. The analysis found common categories across the focus group data that explain the phenomenon of LGBT senior housing. The average age of the participants was 71. Demographic differences were found between generations, with the older participants being more likely to have revealed their sexual orientation late in life, and more likely to have been married and have children. The findings showed that acceptance by other residents of one's sexual orientation and gender identity allows LGBT seniors to feel comfortable in what several residents called their "domestic environment." The questions asked about housing choice and were open ended; respondents chose to focus on the social aspect of their living environments. Acceptance, as opposed to tolerance, was a strong theme. Acceptance by others reduced stress and fostered a feeling of safety and a sense of community. Social networks were strong and expansive, contrary to the theory of socioemotional selectivity theory, which would argue that the total number social relationships diminishes with age. Participants emphasized the social context of their living environment as the reason they chose to live in LGBT senior housing. Participants noted past discrimination, but it was the positive aspects resulting from acceptance that were emphasized as the reason for their choice of LGBT specific retirement housing.