Dissertations / Theses on the topic 'MC3D'

L'explosion de vapeur est l'un des phénomènes les plus critiques et complexes qui peuvent se produire lors d'un accident grave dans une centrale nucléaire. Le code MC3D est reconnu comme une référence pour l'évaluation de ce phénomène. Ce phénomène explosif est analogue à une détonation. L'explosion est due à la fragmentation du combustible fondu, au passage de l'onde de choc et à la libération très rapide de l'énergie associée. Cependant, les mécanismes précis du processus de pressurisation sont très incertains et ont fait l'objet de travaux réalisés dans le cadre du programme RSNR-ICE (2014-2023), qui ont permis de mieux comprendre la phénoménologie générale et de valider le principe général de MC3D, basé sur un principe d'ébullition directe autour de la surface des fragments de corium via un mécanisme d'ébullition en film. Or, il apparaît que les processus de fragmentation semblent, dans certaines conditions, se réaliser sans une dispersion significative des fragments dans l'eau, ce qui est contraire à ce que présuppose le modèle MC3D actuel. L'objectif de la thèse est de proposer une modélisation améliorée de l'explosion pour MC3D, combinant le principe actuel d'ébullition directe et d'interaction combustible-refroidissement localisée dans un petit volume autour des gouttes de corium et des fragments. Après une bibliographie extensive du phénomène d'explosion de vapeur, une analyse détaillée du comportement du modèle MC3D actuel est effectuée, en utilisant un cas-test simple et idéal. Malgré la simplicité de l'ensemble de données, l'analyse peut être directement appliquée aux expériences à géométrie unidimensionnelle telles que KROTOS. Le rôle crucial du vide initial et du vide créé est mis en évidence ; il suggère également les premiers contours d'un nouveau modèle. Le logiciel Basilisk a ensuite été utilisé pour effectuer des simulations DNS afin d'obtenir des détails sur les transferts thermiques de fragmentation et d'association. Une analyse complète des régimes de fragmentation, des statistiques incluant le diamètre moyen de Sauter et la fonction de densité de probabilité de la masse et de la surface des fragments, du nombre de Nusselt transitoire et du coefficient de traînée a été menée. Dans le même temps, les résultats du même cas d'essai utilisant MC3D sont comparés à ceux de Basilisk, ce qui met en évidence la nécessité de modifier le modèle MC3D. Enfin, les grandes lignes d'un nouveau modèle proposé sont présentées et discutées. Celles qui ont pu être validées directement à partir des résultats du DNS ont été implémentées dans la version actuelle de MC3D. Il s'agit en particulier de l'introduction d'une Micro-Interaction de Non-Equilibre (NEMI), Les autres propositions concernant le comportement du vide pourront être implémentées dans la future version (V4) du code
The steam explosion is one of the most critical and complex phenomena that may occur during severe accident in a Nuclear Power Plant. The MC3D computer code is recognized as reference for the evaluation of this phenomenon. This explosive phenomenon is analogous to a detonation. The explosion is due to the fragmentation of the molten fuel, the passage of the shock wave and the very fast release of the associated energy. However, the precise mechanisms of the process of pressurization are very uncertain and have been the subject of works carried out under the program RSNR-ICE (2014-2023), which led to an increased understanding of general phenomenology and validated the general principle of MC3D, based on a principle of direct boiling around the surface of the corium fragments via a film boiling mechanism. However, it appears that the fragmentation processes seem, under certain conditions, to be achieved without a significant dispersion of the fragments in the water, which is contrary to what presupposes the current MC3D model. The aim of the thesis is to propose an improved modeling of the explosion for MC3D, combining the current principle of direct boiling and fuel-coolant interaction localized in a small volume around the corium drops and fragments. Following an extensive bibliography of the steam explosion phenomenon, a detailed analysis of the behavior of the current MC3D model is performed, using a simple and ideal test-case. Despite the simplicity of the data set, the analysis can be directly applied to experiments with one-dimensional geometry such as KROTOS. The crucial role of initial and created void is highlighted; It also suggests the first outlines of a new model. The Basilisk software was then used to perform DNS simulations to get details of fragmentation and association heat transfers. Comprehensive analysis about fragmentation regimes, statistics including Sauter Mean Diameter and Probability Density Function of fragment mass/area, the transient Nusselt number and drag coefficient were conducted. At the same time, results for the same test-case using MC3D are compared with that of Basilisk, highlighting the need of modification of MC3D model. Finally, the main lines of a proposed new model are presented and discussed. Those that could be directly validated from the DNS results were implemented in the current MC3D version. This concerns in particular the introduction of a Non-Equilibrium Micro-Interaction (NEMI), The other proposals concerning the behavior of the void may be implemented in the future version (V4) of the code

Lors d’un accident grave dans un réacteur nucléaire (REP ou REB en particulier), le combustible fondu (corium) peut se déverser dans le réfrigérant (eau). L’interaction entre les deux fluides est appelée Interaction Combustible-Réfrigérant. Sous certaines conditions, cette interaction peut conduire à une «explosion de vapeur» qui peut menacer le confinement du réacteur nucléaire. L’ICR est une interaction de caractère multiphasique complexe où divers phénomènes physiques interviennent de manières couplées. Elle débute par une phase de mélange entre les fluides (prémélange), se traduisant par la fragmentation du corium et sa dispersion dans le réfrigérant. Ce processus de fragmentation impacte les échanges thermiques (ébullition et mise en mouvement du fluide environnant (réfrigérant)) et les processus chimiques (oxydation du corium et génération d’hydrogène). Cette thèse apporte de nouveaux éléments concernant la compréhension physique et la modélisation du phénomène de fragmentation du corium, dont l’objectif principal est d’améliorer la modélisation dans le logiciel de thermohydraulique multiphasique MC3D, développé par l’IRSN. L’étude proposée se base sur l’hypothèse de la modélisation de la fragmentation comme un phénomène multi-échelle avec un découplage entre taux de fragmentation du jet et dimension des gouttes résultantes. Elle suppose un processus de fragmentation qui est le résultat d’une déstabilisation primaire (passage jet -> grosses gouttes) pilotée par les grandes échelles de l’écoulement et d’un processus de déstabilisation secondaire menant à une fragmentation finale dépendante des paramètres plus «locaux» de l’écoulement. Nous avons conjugué notre modélisation avec une méthode de type MUSIG récemment introduite dans le logiciel MC3D. Les gouttes de corium y sont représentées, via un découpage en classes, par plusieurs champs de masse et d’énergie avec des diamètres distincts. Malgré les avancées dans la modélisation de la fragmentation, la compréhension des mécanismes et la caractérisation de la fragmentation des gouttes liquides est encore très imparfaite, particulièrement dans le cas liquide/liquide. Le travail de thèse s’est alors orienté vers l’analyse de ce processus en utilisant le logiciel de simulation GERRIS. L’étude conduit à proposer une nouvelle carte de régimes de fragmentation en configuration liquide/liquide, une compréhension plus approfondie de la dynamique de fragmentation et une analyse sur l’interaction vortex-goutte pilotant la transition entre les régimes
In the case of a severe accident in a nuclear power plant, the molten core may flow into water and interact with it. The consequences of this fuel-coolant interaction (FCI) for the follow-up of the accident may be numerous so the phenomenon needs to be described accurately, one of them called “steam explosion” can lead to the failure of the nuclear reactor containment. FCI is a complex multiphase interaction involving several physical phenomena. The premixing phase of the interaction consists in the fragmentation and dispersion of corium in the coolant pool. This phase is driven by the fragmentation process which modifies heat transfers (coolant boiling dynamics) and chemical reactions (corium oxidation and hydrogen generation). This thesis brings new elements about the corium jet and droplet breakup with the main goal of improve fragmentation models on the MC3D multiphase code, developed by the IRSN. Our study is based on a multi-scale fragmentation process where the jet fragmentation rate and final droplet dimensions are not coupled themselves. We suppose a fragmentation process resulting from a primary instability (mass transfer within jet and big droplets) depending on the large flow scales and a secondary instability depending on the small flow scales (leading to final droplet breakup). This model has been implemented in MC3D in combination with the MUSIG method recently added to MC3D. In this method, droplets are represented using several classes, each of them with their own droplet diameter, mass and energy fields. Despite new improvements on modeling corium fragmentation, there is still a lack on the comprehension and characterization on the liquid droplet fragmentation, particularly on liquid/liquid configurations. In this thesis, we study in detail droplet breakup using the computational fluid dynamics software GERRIS. As a result, we find a new droplet breakup classification in liquid/liquid configurations, we improve the droplet breakup dynamics comprehension and we analyze the droplet-vortex interaction to determine breakup regime transition

Melanocortins (MCs) play an important role in feeding, metabolism, and energy expenditure. While melanocortin receptor (MCR) mRNA has been found in the mesolimbic dopamine (DA) pathway, the ability of melanocortins to regulate feeding and other behaviors through actions on the mesolimbic DA system have not been examined. Short-hairpin RNAs (shRNAs) were created targeting MC3R and MC4R and were tested via in vitro studies for their ability to knockdown their target receptor. A total of three shRNAs were created targeting each receptor, and each shRNA caused successful knockdown. These shRNAs are tools that can be used for future in vivo studies to examine the various behavioral effects of melanocortins on the mesolimbic DA pathway.

Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Schaefer, Dirk; Committee Member: Panchal, Jitesh; Committee Member: Paredis, Chris; Committee Member: Rosen, David; Committee Member: Yoder, Douglas. Part of the SMARTech Electronic Thesis and Dissertation Collection.

In this thesis, several new optical fibre devices are described. These devices are based on fibres with special structures or materials, fabricated by the MCVD technique. Light propagation and intermodal coupling in twin-core (TC) fibres are investigated both theoretically and experimentally. A cascaded TC fibre filter is demonstrated and so are TC fibre intermodal couplers using both mechanical gratings and fibre acoustic flexural waves, which can be used as filters, wavelength-division multiplexing (WDM) taps and frequency shifters. Photosensitivity in both transition-metal-doped fibre and cerium-doped fibre with applications for making fibre in-core gratings are also studied. UV-induced absorption and refractive index change are investigated. A large absorption change occurs when fibre is exposed to pulsed UV. The fibre IR loss eventually recovers to its original level. The UV-induced refractive index change in cerium fibre is found to be the same order of magnitude as that reported in germanosilicate fibres. Some other devices and effects, including a gold-implanted fibre polariser, excitation poling in second harmonic generation and a spatial model converter, are also studied. The gold-implanted polariser is much easier to be massproduced and spliced to an ordinary fibre with a low loss than its liquid-metal-implanted counterpart. Excitation poling gives an improved efficiency in second harmonic generation. The spatial model converter provides an easy low-loss connection for waveguides with different spatial modes.

Medullary cystic kidney disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) are autosomal dominant renal disorders characterized by tubulo-interstitial fibrosis, hyperuricemia and medullary cysts . They are caused by mutations of the UMOD gene, encoding uromodulin Tamm Horsfall protein, the most abundant protein in urine . Uromodulin is a glycoprotein that is exclusively expressed by epithelial tubular cells of the thick ascending limb of Henle's loop and distal convoluted tubule. The majority of the mutations so far reported involve one of the 48 conserved cysteine residues. It has been shown that cysteine-affecting mutations could lead to partial endoplasmic reticulum (ER) retention thus causing defective intracellular trafficking of uromodulin. Materials and methods: we have investigated 3 families showing characteristics of the FJHN/MCKD phenotype. In the first two families the diagnosis of FJHN/MCKD was based on the familial occurrence of chronic renal disease associated with or preceded by early onset of hyperuricemia, however in the third family, which there wasn't familial story of chronic renal disease, the diagnosis was based on early onset of hyperuricemia, chronic renal insufficiency, and renal malformations. Results: We reported- for the first time- the association of tow novel UMOD mutations (Trp202Arg and Gly131Asp) in the proband of the first family, which was a compound heterozygous for these two mutations. The first mutation was inherited from the mother which was affected of FJHN/MCKD, and the second mutation was inherited from an apparently healthy father, and was fuond in her apparently healthy brother. However UMOD mutations were not fuond in the members of second and third family. Conclusions: From the study of these 3 families we have get new insights in the molecular biology of UMOD gene: 1- Double mutant individuals occur in FJHN/MCKD. We identifided , for the first time, the presence of two UMOD mutation in one patient, as compound heterozygous for 2 UMOD mutation. 2- Amino acids substitution not involving Cysteine residues cause ER retention. 3- A non conservative amino acid substitution, that functional behaves as a normal allele, i.e. it is not able to induce ER retention, is not associated with FJHN/MCKD diseases, rather it might be associated with intermediate phenotypes ( reduction of F E uric acid, hypertension). 4- We confirmed that UMOD mutations are not the only cause of the FJHN/MCKD phenotype.
L’Uromodulina (Tamm-Horsfall protein) è una proteina che si trova normalmente in quantità abbondante nelle urine. Le mutazioni del gene che codifica l’Uromodulina (gene UMOD) sono associate con la Familiar Juvenile Hperuricemic Nefropathy (FJHN) e la Medullary Cystic Kidney Disease tipo 2 (MCKD2), che si manifestano con iperuricemia e gotta, ridotta escrezione frazionaria dell’acido urico, insufficienza renale cronica. L’eta’ di esordio è nell’infanzia per la FJHN, mentre la MCKD2 esordisce attorno ai 30 anni con ridotta concentrazione urinaria, iperuricemia, insufficienza renale cronica e si associa a cisti renali. FJHN/MCKD2 sono malattie autosomiche dominanti, con quadro istologico di nefropatia interstiziale. Alcuni autori le considerano una malattia unica. La maggior parte delle mutazioni di UMOD descritte in letteratura modificano uno dei 48 residui di cisteina. Queste mutazioni alterano la struttura terziaria causando accumulo intracellulare e conseguente disfunzione tubulare. Materiali e metodi: Abbiamo studiato 3 famiglie presentano il fenotipo della sindrome di FJHN/MCKD: nelle due prime famiglie una storia familare con una importante ricorrenza di iperuricemia e IRC, ma nella treza famiglia, nonostante, l'assenza della familiarità per patologia renale, la presenza dell'insufficienza renale e l'iperuricemia, hanno confermato la diagnosi della sindrome di FJHN/MCKD. L’analisi genetica è stata effettuata sulla DNA genoma, e tuuti gli esoni del UMOD gene, e HNF1B gene sono stati sequenziati. Risultati: Nella prima famiglia: l’analisi genetica evidenziava la presenza di due mutazioni missenso di UMOD, mai descritte precedentemente. Quindi il probando è eterozigote composto per due mutazioni: l’una UMODc 392 G>A Trp202Arg ereditata dalla madre affetta anch’essa da FJHN, l’altra UMODc 604 T>C Gly131Asp ereditata dal padre e presente anche nel fratello del probando, ambedue (padre e fratello) tuttavia asintomatici per questa malattia. Nella seconda e terza famiglia, non sono stati identificati mutazioni per UMOD gene, neanche per HNF1B gene. Conclusione: il caso clinico ci permette di acquisire nuove informazioni sulla patologia molecolare di UMOD: - è possibile trovare due UMOD mutazioni in un paziente affetto dalla sindrome FJHN/MCKD. -Sostituzione in residui non cisteinici sono in grado di indurre accumulo intracellulare di uromodulina e conseguentemente la nefropatia. -Varianti aminoacidiche che non causano l’accumulo di uromodulina, non causano la nefropatia ma potrebbero essere associate ad ipertensione, come recentamente evidenziato in altri lavori scientifici. - Le mutazioni del UMOD gene non sono l'unica causa della sindrome FJHN/MCKD.

L'objet de cette thèse est d'appréhender qualitativement les effets macroéconomiques des allocations chômage. Deux questions sont plus particulièrement au cœur de nos préoccupations : la comparaison positives des régimes d'assurance et d'assistance chômage, qui est au cœur de la deuxième partie, et la détermination de la générosité globale des allocations chômage, qui est au cœur de la troisième partie. La première partie de la thèse dresse un état des lieux des contributions existantes. Dans le premier chapitre, nous nous concentrons sur des modèles ou ce sont les comportements des individus qui déterminent leur probabilité d'être au chômage, alors que dans le chapitre 2, le chômage est due à la formation non concurrentielle des salaires. Dans les deux autres parties de la thèse, nous nous plaçons dans le cadre d'un modèle de négociations salariales dynamiques ou l'effort de recherche d'emploi des individus n'intervient pas. Dans le chapitre 3, nous montrons que la dégressivité des allocations chômage peut aggraver le taux de chômage d'équilibre. Dans le chapitre 4, nous montrons que l'indexation de l'assurance chômage sur les derniers salaires négociés accroit la pression salariale et le chômage. Le chapitre 5 détermine alors le niveau des allocations chômage qui maximise différents critères de bien-être. Le ratio de remplacements optimal pour les travailleurs au chômage est supérieur à celui des travailleurs employés, qui est lui-même supérieur à celui qui maximise la somme des utilités des travailleurs. Enfin, le ratio de remplacement qui maximise les profits est nul. Le dernier chapitre de la thèse introduit un modèle de vote afin de comprendre pourquoi les agents choisissent un niveau d'allocations chômage qui entraine un niveau de chômage positif. On met alors en évidence une relation négative entre le taux de chômage et le ratio de remplacement des allocations chômage
In this dissertation, I try to give a better qualitative understanding of the macroeconomic effects of unemployment benefits. The two most important question i ask is the comparison of the positive properties of unemployment insurance and of unemployment assistance, which constitute the second part of the dissertation, and the determination of the global generosity of unemployment benefits, which constitute the third part of the dissertation. The first part propose a survey of the literature. In the first chapter, i focus on models where the probability of being unemployed depends only on individuals' behaviour while in the second chapter, unemployment arises because of imperfect competition in the wage setting. In the two other parts of the dissertation, i use a dynamical wage bargaining model in which search effort does no matter. In chapter 3, i show that the digressiveness of unemployment benefits might increases the unemployment rate. In chapter 4,1 show that indexing unemployment benefits on past wage earned increases the wage pressure and the equilibrium unemployment. Chapter 5 looks at the level of the replacement ratio that maximises different steady-state welfare criterions. The optimal replacement ratio according to unemployed workers is higher than the one according to employed workers, which is itself higher than the one according to the sum of utility of every workers. At last, the replacement ratio that maximises profits is null. The last chapter introduces a voting process on the level of the replacement ratio so as to understand why rational agents supports levels of replacement ratio that leads to a positive level of the unemployment rate. We prove the existence of a negative relation between the unemployment rate and the replacement ratio

The master’s thesis focuses on a process contaminant 3-MCPD (3-chloropropane-1,2-diol), which is formed during food processing. The first part of the thesis summarizes scientific knowledge about its chemical and physical properties, toxicity, occurrence in food and methods of analysis. In the second part is monitored the content of 3-MCPD in barley, in standard and special types of malts and beer. Samples were derivatized with phenylboronic acid (PBA) and 3-MCPD derivatives were analyzed by gas chromatography with a mass detector. Deuterated 3-MCPD was used as an internal standard. The limit of quantification was 1 gkg-1 for barley and malt samples and 10 gkg-1 in case of beer. The barley samples contained concentration of 3-MCPD below LOQ. In samples of malt was found concentration

Approved for public release; distribution is unlimited.
The Mobile CubeSat Command and Control (MC3) program will become the ground segment of the Colony II satellite program. The MC3 ground station contains Commercial Off-the-Shelf (COTS) hardware with Government Off-the-Shelf (GOTS) software making it an affordable option for government agencies and universities participating in the Colony II program. Further, the MC3 program provides educational opportunities to students and training to space professionals in satellite communications. This thesis analyzes the MC3 program from the program manager's point of view providing a Concept of Operations (CONOPS) of the program as well as initial analysis of MC3 ground station locations. Also included in this thesis is a future cost analysis of the MC3 program as well as lessons learned from the NPS acquisition process.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
Modelos CAD 3D são ferramentas utilizadas na indústria para planejamento e simulações antes da construção ou realização de tarefas. Em muitos casos, como por exemplo na indústria de óleo e gás, esses modelos podem ser massivos, ou seja, possuem informações detalhadas em larga escala no intuito de que sejam fontes de informações precisas. Para obtenção de navegação interativa nesses modelos é necessária uma combinação de hardware e software adequados. Mesmo hoje com GPUs mais modernas, a renderização direta desses modelos não é eficiente, sendo necessárias abordagens clássicas como descarte de objetos não visíveis e LOD antes de enviar os dados à GPU. Logo, para renderização em tempo real de modelos CAD massivos são necessários algoritmos e estruturas de dados escaláveis para processamento da cena de forma eficiente. O trabalho dessa tese propõe o MCAD (Massive Computer-Aided Design) Shape grammar, uma gramática expansiva que gera objetos para criar cenas 3D de modelos massivos de forma procedimental. Nos últimos anos, modelagem procedimental tem ganhado atenção para criar cenas 3D rapidamente utilizando uma representação compacta, que armazena regras de geração ao invés de representação explícita da cena. MCAD Shape grammar explora repetições e padrões presentes em modelos massivos para renderização de cenas, reduzindo o consumo de memória e processando a cena procedimentalmente de forma eficiente. Convertemos modelos reais de refinarias em MCAD Shape grammar e implementamos um renderizador para os mesmos. Os resultados mostraram que esta solução é escalável com alto desempenho, além de ser a primeira vez que modelagem procedimental é utilizada nesse domínio.
3D CAD models are tools used in the industry for planning and simulations before construction or completion of tasks. In many cases, such as in the oil and gas industry, these models can be massive, that is, they have large-scale detailed information in order to be sources of accurate information. Interactive navigation in these models requires a combination of appropriate hardware and software. Even nowadays with modern GPUs, the direct rendering of these models is not efficient, requiring classic approaches such as culling non-visible objects and LOD before sending the data to the GPU. Therefore, for real-time rendering of massive CAD models, we need scalable algorithms and data structures to efficiently process the scene. The work of this thesis proposes MCAD (Massive Computer-Aided Design) Shape grammar, an expansive grammar that procedurally generates objects to create 3D scenes of massive models. In recent years procedural modeling has drawn attention for quickly creating 3D scenes using a compact representation, which stores generation rules rather than explicit representation of the scene. MCAD Shape grammar explores repetitions and patterns present in massive models for rendering scenes, reducing memory footprint and procedurally processing the scene efficiently. We converted real refinery models into MCAD Shape grammar and implemented a renderer for them. Results showed that our solution is scalable with high performance, also it is the first time that procedural modeling is used in this domain.

3-monochloropropane-1,2-diol or 3-chloropropane-1,2-diol (3-MCPD) and glycidol are the most commonly occurring group of thermal process contaminants which are considered as “possible human carcinogen” and “probably carcinogenic to humans”, respectively. Potato strips prepared from three different potatoes cultivars (Russet Burbank, Ranger Russet, and Umatilla Russet) grown in North Dakota from the crop year 2018 were fried with vegetable oil at 190 ºC, respectively, for five consecutive days (8 h/day). The dynamic changes of 3-MCPD and glycidol equivalents were investigated during deep-fat frying. 3-MCPD equivalent in oil and potato strips decreased with increased frying time. Meanwhile, the content of glycidol equivalent increased with increased frying time. The major 3-MCPD and glycidol equivalents that were detected in the fried potato strips were those that migrated from the oils during frying. The application of absorbents, i.e., Magnesol and Celite, achieved the mitigation of 3-MCPD and glycidol in frying oil.

Thesis (MScMedSc (Biomedical Sciences))--University of Stellenbosch, 2010.
Thesis presented in partial fulfillment of the requirements for the degree Master of Science in Medical Biochemistry at the University of Stellenbosch.
Bibliography
ENGLISH ABSTRACT: Tuberculosis (TB) is an infectious disease which has plagued society for thousands of years. Despite public health programs, anti-TB drugs and a vaccine, the absolute numbers of people infected with TB each year continue to rise as populations grow. The high TB-burden areas are also plagued by other debilitating factors including HIV/AIDS infection, poverty and malnutrition. Nutrition has been implicated in TB susceptibility in a number of studies. While most are observational reports made during times of war, famine or natural disaster, multiple studies provide convincing evidence for poor nutritional status increasing the morbidity and mortality of TB. Numerous approaches are currently utilized in TB research, and there has been convincing evidence to support the role of host genetics in TB susceptibility. Based on previous linkage studies and a search of current literature, three genes were selected for this case-control study. Subsequently, variations located in cathepsin Z (CTSZ), melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) were genotyped in the South African Coloured (SAC) population to determine the existence of an association with TB disease. CTSZ is a lysosomal cysteine protease expressed in cells of the immune system. Interaction between this 303 amino acid protein and β2 integrin receptors lymphocyte function-associated antigen-1 (LFA-1) and macrophage antigen-1 (MAC-1) leads to altered lymphocyte proliferation. As a result, a single exonic variant in CTSZ, rs34069356, the same identified in a previous linkage study, showed strong evidence for association with TB susceptibility in cases (n = 410) and controls (n = 301) in the SAC population (p< 0.0001). MC3R and MC4R are two of 5 melanocortin receptors. MC3R has been found to be a key regulator in energy expenditure and host metabolism while activation of MC4R leads to a decrease in food intake. Activation of these two receptors is regulated by leptin, a hormone released by adipose tissue. A variant located upstream of the MC3R gene, rs6127698, also showed evidence of disease association with the less frequent allele, T, being under-represented in cases (n = 540) compared to controls (n = 541) (genotypic frequency, p = 0.0039), suggesting a possible resistance phenotype. Functional analysis of this variant revealed an increase in MC3R expression when stimulated with BCG, with individuals homozygous for the T allele exhibiting an even larger upregulation of MC3R expression than individuals homozygous for the G allele, though this difference was not statistically significant. A single haplotype in MC3R was found to be associated with TB susceptibility (p = 0.0008) and this association remained after permutation testing to correct for multiple testing (p = 0.0061) Three variants were selected for genotyping in MC4R and while none of these showed a statistically significant difference between cases (n = 510) and controls (n = 487), this gene should not be ruled out as both MC3R and MC4R have been found to work closely though not redundantly and double knockout experiments result in exacerbated obesity, suggesting that these proteins have a synergistic effect. The results of this study support both a role of host genetics and nutritional status in TB and strongly motivate further research in both of these fields.
AFRIKAANSE OPSOMMING: Tuberkulose (TB) is ‘n aansteeklike siekte wat reeds vir eeue die gesondheid van die publiek bedreig. Ten spyte van publieke gesondheidsprogramme en verskeie anti-TB medikasie middele, groei die aantal van mense wat hiermee ge-infekteer word steeds jaarliks. Dit is veral in areas waar TB steeds groei, waar ook ander neerdrukkende faktore soos HIV/Vigs, armoede en wanvoeding hoogty vier. Na aanleiding van verskeie verslae tydens oorloë, hongersnood en ander natuulike rampe is dit veral duidelik dat swak nutriënt inname morbiditeit en sterftes wat met TB gepaard gaan verhoog. Talle benaderings word tans gebruik in TB-navorsing, Bewyse is oortuigend om die rol van genetika van die gaheer met vatbaarheid vir TB te verbind. Op grond van vorige studies en die huidige literatuur, het ons drie gene gekies vir hierdie pasiënt-kontrole studie. Variante geleë in cathepsin Z (CTSZ), melanocortin 3 receptor (MC3R) en melanocortin 4 receptor (MC4R) is ge-genotipeer in die Suid-Afrikaanse Kleurling bevolking (SAK) (540 gevalle en 540 kontrole) om sodoende die assosiasie met TB te bepaal. CTSZ is ‘n lisosomale sisteïen protease wat uitgedruk word in immuunselle. Interaksie tussen hierdie 303 aminosuur protein en β2 integrin reseptore nl. LFA-1 en MAK-1 bring veranderde limfosiet proliferasie mee. ‘n Enkele eksoniese variant in CTSZ, rs34069356, dieselfde soos ge-identifiseer in ‘n vorige studie, verskaf sterk bewys vir assosiasie met TB vatbaarheid in gevalle (n = 410) en kontrole (n = 301) in die SAK bevolking. MC3R en MC4R is twee van 5 melanokortien reseptore. Daar is gevind dat MC3R 'n sleutelrol speel in die energie regulering van gasheer metabolisme, terwyl die aktivering van MC4R eindelik lei tot 'n afname in voedsel inname. Aktivering van hierdie twee reseptore word gereguleer deur Leptien, 'n hormoon wat vrygestel word deur adipose weefsel, ‘n Variant, stroomop geleë vanaf MC3R, rs6127698, is ook bewys om met TB ge-assosieer te wees, met die T-alleel meer seldsaam in gevalle (n = 540) as in kontroles (n = 541) wat dui op 'n moontlike weerstandsfenotipe. Funksionele analise van hierdie variant onthul 'n toename in MC3R uitdrukking wanneer gestimuleer met BCG, met individue homosigoties vir die T-alleel wat selfs groter opregulation veroorsaak wanneer vergelyk word met individue homosigoties vir die G allele. Hierdie resultaat was egter nie statisties beduidend nie. 'n Enkele haplotiepe in MC3R is ge-assosieer met TB vatbaarheid en die assosiasie is onveranderd nadat ‘n permutasie korreksie aangebring is (p = .0061). Voorts is drie variante gekies vir genotipering in MC4R en ten spyte daarvan dat nie een daarvan 'n statisties beduidende verskil getoon het tussen pasiënte (n = 510) en kontroles (n = 487) nie, behoort hierdie geen nie uitgesluit word nie, Die rede hiervoor is dat beide MC3R en MC4R verskeie kere gevind is om in samewerking ‘n rol te speel om vetsug te voorkom of te vererger. Die resultate van hierdie studie beaam beide 'n rol van gasheer genetika en voedingstatus in TB en motiveer veral verdere navorsing in beide van hierdie vakgebiede.

Orientador: Normonds Alens
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Campinas
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Abstract: Not informed.
Doutorado
Doutor em Engenharia Elétrica

Recently, as a promising lighting source, light-emitting diodes (LEDs) have become more and more attractive and have great opportunity to replace traditional lighting sources - incandescent, fluorescent and HID because of the advantages such as high luminous efficacy, long lifetime, quick on/off time, wide color gamut, eco-friendly etc. Based on the research from U.S. Department of Energy, over 30% of total electric consumption in U.S. each year is for lighting, 75% of which are for indoor lighting (including both residential and commercial buildings). In the indoor LED lighting application, to provide multiple current source outputs for multiple LED strings, traditional solutions usually adopt a two-stage structure, which is complicated and cost-ineffective. How to design a simple, low-cost and efficient LED driver with multiple current source outputs is in great demand and really challenging. In this thesis, a single-stage multi-channel constant current (MC3) LED driver structure has been proposed. Multiple transformer structure is utilized to provide multiple current source outputs. The current control scheme is also simple - only one LED string current is sensed and controlled; other strings' currents are cross regulated. Firstly, a PWM half bridge topology is chosen to implement the proposed single-stage MC3 LED driver concept. In order to analyze the current cross regulation, a general model is derived. The circuit has been simulated under various LED load conditions to verify its good current sharing capability. In order to further improve efficiency, simplify the driver's complexity and reduce cost, a LLC resonant topology is also investigated. LLC current gain characteristic has been derived by considering LED's i-v character and a design procedure is developed. A 100 kHz, 200 W, 4-string MC3 LLC LED driver is designed and tested. The experimental results show that the driver can maintain constant current output within the whole input and output variations, achieve good efficiency and realize current sharing under both balanced and unbalanced LED conditions. The dimming function can also be realized through frequency modulation method and burst mode control method. As a conclusion, a single-stage MC3 LED driver concept is proposed and implemented with two topologies. The proposed idea provides a simple, low-cost and efficient solution for indoor LED lighting application with multiple LED string configuration. It also has good current sharing capability and robustness to LED forward voltage variations or short failures.
Master of Science

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The Mobile CubeSat Command and Control (MC3) architecture is a growing network of ground stations that spans the United States of America. It was designed to support the National Reconnaissance Office’s Experimental CubeSat Program. Each node was originally designed to communicate via UHF and S-band frequencies using Yagi antenna only. The MC3 ground station at the Naval Postgraduate School has recently incorporated a 3-meter S-band dish. This thesis documents the calibration and capabilities of the new S-band dish. It also investigates the possibility of using the antenna outside of its normal operating range. In particular, the idea of using an S-band, 3-meter dish to receive UHF band signals was tested by designing a UHF signal feed optimized for 915 MHz and used to listen to a UHF source deployed on a high altitude balloon at near orbital distances. In addition, this document discusses the integration of a dish system into current and future MC3 ground stations.

Background: Generating evidence to inform care for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency requires sustainable and integrated measurement of priority outcomes. Methods: From an existing Canadian cohort study, we evaluated the quality of metabolic clinic chart-abstracted data for measuring core outcomes for pediatric MCAD deficiency. We then modelled variation in emergency department (ED) use, in association with disease severity, child age, and distance to care. Results: Children with MCAD deficiency visit the metabolic clinic at least annually on average but we identified data quality challenges related to inconsistent definitions of core outcomes and missing information in patient charts. Rates of ED use were highest among children aged 6 to 12 months, with more severe disease, and living closest to care. Conclusion: While measuring core outcomes through the metabolic clinic for children with MCAD deficiency is feasible, harmonized data collection is needed to evaluate care and further understand ED use.

Aims: To determine improvements in third metacarpal (Mc3) condylar microanatomy attributable to preconditioning exercise. To investigate developmental causes of Mc3 condylar fracture. Methods: Twelve Thoroughbred horses were raised at pasture; six received preconditioning exercise from 10 days. Calcein labels were administered 19 and 11 days prior to euthanasia at 18 months. Six horses also received 2 seasons of race-training and were euthanised at 3 years. Slices were taken from the distal Mc3 condyle in the frontal and dorsal- and palmar-oblique frontal planes, scanned with DXA and macerated (frontal slices) or embedded in PMMA (oblique slices). Articular calcified cartilage (ACC) and subchondral bone (SCB) in oblique slices were imaged using confocal scanning light microscopy and quantitative backscattered electron scanning electron microscopy. ACC and SCB in the palmar slice lateral parasagittal grooves were imaged using μCT and nanoindentation tested. Results: Characteristic spatial variations in ACC and SCB histomorphometric parameters were present, none of which was significantly related to preconditioning exercise. Thickened, aberrantly mineralised ACC was found in 13/24 parasagittal grooves in the palmar slices and on the sagittal ridge of 4/12 dorsal slices of 18-month-old horses. Deep to thickened ACC, SCB had an open marrow structure, having not adopted the buttress morphology of the normal SCB plate. SCB in 3-year-old horses had incorporated early ACC defects as notches in parasagittal grooves and a hyaline cartilage island in a sagittal ridge. ACC was less stiff and SCB more stiff in affected than unaffected parasagittal grooves. Chondroclastic resorption in the parasagittal groove may be retarded as early as 3-6 months, possibly due to localised inhibition of ACC mineralisation. Linear defects in the Mc3 parasagittal groove may develop prior to entry to race training and are not significantly affected by preconditioning exercise. Early identification of affected individuals should aid in reducing condylar fracture risk.

Este trabajo de investigación aborda el problema de falta de robustez, mediante el reemplazo de la matriz de covarianzas obtenida con el método clásico, por la matriz de covarianzas obtenida con el método robusto MCD (Todorov y Filzmoser, 2009). El método robusto MCD: Minimun Covariance Determinant, consiste en realizar las estimaciones para el vector de medias y la matriz de covarianzas a partir de la selección de una submuestra obtenida del remuestreo del conjunto de datos en estudio, cuya característica principal es que tiene la matriz de covarianzas con determinante mínimo. Muchas veces, el análisis estadístico en presencia de datos atípicos, mediante métodos clásicos, puede llevar a conclusiones erróneas debido a la sensibilidad de dichos métodos, por ello el objetivo del presente trabajo es presentar la metodología de los estimadores MCD, a fin de conseguir una “matriz de covarianzas robustificada” la cual será utilizada para realizar el Análisis de Componentes Principales en conjuntos de datos con presencia de observaciones atípicas. Se ilustra la metodología de la teoría y la aplicación para dos conjuntos de datos, resultados de investigaciones en la Botánica (Quinteros, 2010 y Gómez, et. al., 2008), se analiza el comportamiento de las Componentes Principales con la metodología MCD y se compara con la metodología clásica. Se determina que las Componentes Principales obtenidas por el método de MCD permiten encontrar mejores indicadores para los conjuntos de datos que tienen valores atípicos. -- Palabras clave: Minimum Covariance Determinant, MCD, Componentes Principales, Estimación Robusta, Matriz de Varianzas y Covarianzas.
--- This research addresses the problem of lack of robustness, by replacing the covariance matrix obtained with the classical method for the covariance matrix obtained with the robust MCD method (Todorov and Filzmoser, 2009). The robust method MCD: Minimun Covariance Determinant, involves making estimates for the mean vector and covariance matrix from the selection of a subsample obtained from the resampling of the data set under study, whose main characteristic is that it has the covariance matrix with the minimum determinant. Many times, the statistical analysis in the presence of outliers, by standard methods, can be misleading because of the sensitivity of these methods, which is why the objective of this paper is to present the methodology of the MCD estimators in order to achieve the "robustified covariance matrix" which will be used to perform Principal Component Analysis on data sets with the presence of outliers. We illustrate the methodology of the theory and application, for two sets of data, research results in the Botany (Quinteros, 2010 and Gomez, et. Al., 2008), we analyze the behavior of the Principal Components with the MCD method and we compare it to the classic methodology. It is determined that the principal components obtained by the MCD method allows to find better indicators for data sets with outliers. -- Keywords: Minimum Covariance Determinant, MCD, Principal Components, Robust Estimation, Scatter Matrix.
Tesis

Orientador: Yuzo Iano
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
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Mestrado
Mestre em Engenharia Elétrica

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FAPES
A galanina (GAL) é um peptídeo composto por 29 aminoácidos que está presente no SNC de inúmeros mamíferos, inclusive do homem. A distribuição da GAL e de seus receptores em estruturas envolvidas com o controle das emoções apontam para um possível papel modulatório desse neuropeptídeo sobre a ansiedade. A Matéria Cinzenta Periaquedutal Dorsal (MCPD) é considerada uma estrutura-chave para a expressão comportamental e autonômica do comportamento defensivo. Entretanto, o papel da GAL nessa estrutura ainda não foi estudado. A MCPD recebe projeções galaninérgicas de outras estruturas, mas não sintetiza o peptídeo em seus corpos celulares. Foram clonados 3 diferentes receptores para a GAL, GALR1 e GALR3, que aumentam o efluxo de K+, e GALR2, que aumenta a concentração intracelular de Ca++. Estudos de imunohistoquímica e hibridização in situ descreveram a presença do GALR1 e do GALR2 na MCPD, embora o GALR1 apareça em maior número. O objetivo do presente estudo foi investigar o envolvimento da GAL sobre a modulação da ansiedade experimental mediada pela MCPD de ratos. Para tanto, foi realizada cirurgia estereotáxica em ratos Wistar adultos para implantação unilateral de uma cânula-guia na MCPD (AP-lambda: 0 mm; L: 2,0 mm; e P: 4,0 mm, 15o), por onde as seguintes drogas foram administradas: GAL (0,1; 0,3; 1,0 e 3,0 nmoles/ 0,2μL), M617 - agonista seletivo GalR1 (0,3; 1,0 e 3,0 nmoles/ 0,2μL) e AR-M1896 – agonista seletivo GalR2 (0,3; 1,0 e 3,0 nmoles/ 0,2μL). Passados 5-7 dias de recuperação, cada animal recebeu a injeção de droga e 20 min. após foi submetido aos testes do LCE, LTE e Vogel. Grupos independentes de animais (n= 5-12) foram usados em cada experimento. A GAL, e os ligantes seletivos M617 e AR-M1896, nas diferentes doses testadas, não alteraram de modo significativo os parâmetros porcentagem de entrada e porcentagem de tempo nos braços abertos (BAs) do LCE. Os resultados mostraram que o tratamento com a GAL (3,0 nmoles) prejudicou a Esquiva 2 de modo significativo, sem alterar a fuga. O tratamento agudo com a GAL não alterou a atividade locomotora verificada no Campo Aberto. E por fim, a GAL (1,0 e 3,0 nmoles) não apresentou diferença para o número de lambidas punidas no Teste do Conflito de Vogel em comparação ao grupo controle. Dessa forma, o efeito tipo-ansiolítico da GAL mediado pela MCPD parece depender do modelo experimental empregado e dos níveis de ansiedade gerados pelo mesmo.
Galanin (GAL) is a 29 amino acids peptide that is present in the CNS of many mammals, including human being. The distribution of GAL and its receptors in emotions control structures involved suggests a possible modulatory role of this neuropeptide on anxiety. The dorsal periaqueductal gray (DPAG) is considered a key structure for behavioral and autonomic expression of defensive behavior. However, the role of GAL in this region has not been studied. The DPAG receives galaninergic projections from other structures, but does not synthesize the peptide on their cell bodies. GAL's actions are mediated by 3 metabotropic receptors, GALR1 and GALR3, which increase K+ efflux, and GALR2, which increases Ca2+ intracellular concentration. Using in situ hybridization technique was described the presence of GALR1 and GalR2 receptors in rat DPAG neurons, but there is GALR1 in greater density. The aim of this study was to investigate the involvement of GAL on the modulation of experimental anxiety by DPAG in rats. Therefore, Wistar rats with a unilateral cannula aimed at the DPAG (AP-lambda: 0 mm; L: 2.0 mm; e P: 4.0 mm, 15o), where the drugs were administered, received the following drugs: GAL (0.1; 0.3; 1.0 e 3.0 nmol/ 0.2μL), M617 – selective agonist GALR1 (0.3; 1.0 e 3.0 nmol/ 0.2μL) e AR-M1896 – selective agonist GALR2 (0.3; 1.0 e 3.0 nmol/ 0.2μL). After 5-7 days of recovery, each animal received an injection of drug and tests were carried-out in the plus-maze, elevated T-maze (ETM) or Vogel Test 20 min later. Each experiment was conducted with separated groups of animals (n=5-12). Tests performed at plus-maze after injection of GAL or selective agonists M617 and AR-M1896 into-DPAG did not change percentage of entries and percentage of time spent in the open arms. The analysis showed that treatment with GAL (3 nmol) significantly impaired Avoidance 2 in the ETM, without change Escape behavior. Acute treatment with GAL did not change locomotion in the Open Field. Finally, GAL (1.0 e 3.0 nmol) did not show difference in the number of punished licks at Conflict Vogel Test in comparison with control group. Thus, the anxiolytic effect of GAL in the DPAG seems to depend on the experimental model of anxiety employee and anxiety level generated by them. Key-words: Galanin. DPAG. Anxiety. T-maze.

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A galanina (GAL) é um peptídeo composto por 29 aminoácidos que está presente no SNC de inúmeros mamíferos, inclusive do homem. A distribuição da GAL e de seus receptores em estruturas envolvidas com o controle das emoções apontam para um possível papel modulatório desse neuropeptídeo sobre a ansiedade. A Matéria Cinzenta Periaquedutal Dorsal (MCPD) é considerada uma estrutura-chave para a expressão comportamental e autonômica do comportamento defensivo. Entretanto, o papel da GAL nessa estrutura ainda não foi estudado. A MCPD recebe projeções galaninérgicas de outras estruturas, mas não sintetiza o peptídeo em seus corpos celulares. Foram clonados 3 diferentes receptores para a GAL, GALR1 e GALR3, que aumentam o efluxo de K+, e GALR2, que aumenta a concentração intracelular de Ca++. Estudos de imunohistoquímica e hibridização in situ descreveram a presença do GALR1 e do GALR2 na MCPD, embora o GALR1 apareça em maior número. O objetivo do presente estudo foi investigar o envolvimento da GAL sobre a modulação da ansiedade experimental mediada pela MCPD de ratos. Para tanto, foi realizada cirurgia estereotáxica em ratos Wistar adultos para implantação unilateral de uma cânula-guia na MCPD (AP-lambda: 0 mm; L: 2,0 mm; e P: 4,0 mm, 15o), por onde as seguintes drogas foram administradas: GAL (0,1; 0,3; 1,0 e 3,0 nmoles/ 0,2μL), M617 - agonista seletivo GalR1 (0,3; 1,0 e 3,0 nmoles/ 0,2μL) e AR-M1896 agonista seletivo GalR2 (0,3; 1,0 e 3,0 nmoles/ 0,2μL). Passados 5-7 dias de recuperação, cada animal recebeu a injeção de droga e 20 min. após foi submetido aos testes do LCE, LTE e Vogel. Grupos independentes de animais (n= 5-12) foram usados em cada experimento. A GAL, e os ligantes seletivos M617 e AR-M1896, nas diferentes doses testadas, não alteraram de modo significativo os parâmetros porcentagem de entrada e porcentagem de tempo nos braços abertos (BAs) do LCE. Os resultados mostraram que o tratamento com a GAL (3,0 nmoles) prejudicou a Esquiva 2 de modo significativo, sem alterar a fuga. O tratamento agudo com a GAL não alterou a atividade locomotora verificada no Campo Aberto. E por fim, a GAL (1,0 e 3,0 nmoles) não apresentou diferença para o número de lambidas punidas no Teste do Conflito de Vogel em comparação ao grupo controle. Dessa forma, o efeito tipo-ansiolítico da GAL mediado pela MCPD parece depender do modelo experimental empregado e dos níveis de ansiedade gerados pelo mesmo.

Given that human development is a complex process involving multiple components and determiningfactors, multidimensional indicators are needed. On the basis of the extensive literatureon the subject, we advance two new indicators: the Matrix of Capabilities and Functioning(MCF), and the Algorithm of Human Development (HDA).The MCF is composed of vectors of capabilities and functionings, based on Sen’s idea of RefinedFunctionings. It is based in a matricial framework, both static and dynamic. The main purposeof constructing this index is to study how different sets of capabilities relate to alternativefunctionings, to produce diverse outcomes.The Human Development Algorithm (HAD) is a multidimensional index concerning the setof goods and services needed to complete a life cycle. The HDA is a socio-economic contextindicator. It is composed of the main «satisfactors» or basic goods and services needed: food,health, education, housing, social security, decent employment and retirement programs, thatmight be available to all throughout of life cycle. This indicator shows the material progressreached by each country or region as well the institutional organization, private and public, andthe degree of social cohesion and solidarity.
Dado que el desarrollo humano es un proceso complejo que tiene múltiples componentes ydeterminantes, es necesario tener indicadores multidimensionales tales como la Matriz de Capacidadesy Desempeños (MCD) y el Algoritmo del Desarrollo Humano (ADH).El MCD está compuesto de vectores de capacidades y de desempeños, basado en la idea de Sensobre desempeños refinados. Está basado en un marco conceptual matricial, tanto estático comodinámico. El propósito principal de la construcción del índice es estudiar cómo diferentes conjuntosde capacidades con desempeños pueden producir distintos resultados.El ADH es un índice multidimensional relacionado con el conjunto de bienes y servicios que senecesitan para completar un ciclo de vida. El ADH es un indicador de contexto socioeconómico.Está compuesto de los principales satisfactores o bienes y servicios básicos que se requieren: alimentos,salud, educación, vivienda, seguridad social, empleo decente y sistema de pensiones, quedeben estar disponibles durante todo el ciclo de vida. Este indicador muestra el progreso materialalcanzado por cada país o región, tanto como la organización institucional pública y privada, yel grado de cohesión social.

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

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A cetamina é um antagonista não competitivo dos receptores glutamatérgicos do tipo N-metil-D-aspartato (NMDA). Estudos pré-clínicos e clínicos têm sugerido que ela apresenta efeito antidepressivo de início rápido e relativamente persistente. O mecanismo de ação envolvido nesse efeito parece ser mais complexo do que o simples bloqueio dos receptores NMDA, envolve a ativação dos receptores α-amino-3-hidroxi-5-metil-4-isoazolepropiônico (AMPA) e da via de sinalização do fator neurotrófico derivado do cérebro (BDNF) e do receptor de tirosina cinase B (TrκB). Diversos fármacos antidepressivos são eficazes no tratamento do transtorno de ansiedade generalizada (TAG) e no transtorno do pânico (TP) somente após tratamento crônico, é possível que a cetamina apresente efeito ansiolítico ou panicolítico de forma rápida e persistente. O labirinto em T elevado (LTE) é um modelo que permite avaliar, no mesmo procedimento, dois tipos de ansiedade: a ansiedade aprendida (esquiva inibitória), relacionada com o Transtorno de Ansiedade Generalizada (TAG), e a ansiedade inata (fuga), relacionada com Transtorno de Pânico (TP). O objetivo do estudo foi investigar os efeitos comportamentais induzidos pela cetamina em ratos expostos ao LTE e o possível envolvimento da via BDNF/ TrκB na MCP (matéria cinzenta periaquedutal) nesses efeitos. Os resultados mostraram que a cetamina de 10 e 30 mg/Kg (doses subanestésicas) administrada de forma aguda não alteraram o comportamento dos ratos no LTE. Já a dose anestésica (80 mg/Kg), prejudicou a fuga 1, o que pode sugerir efeito tipo-panicolítico rápido. Quando a cetamina 10 mg/Kg foi administrada 24 horas antes do teste no LTE, houve facilitação da Fuga 1, o que pode sugerir um efeito tipo-panicogênico tardio. Já a dose anestésica da cetamina administrada 24 horas antes do teste facilitou à esquiva, o que sugere um efeito tipo-ansiogênico tardio, e ao mesmo tempo prejudicou a fuga 1, sugerindo um efeito tipo-panicolítico persistente. E o 5-metil-10,11-dihidroxi-5Hdibenzo(a,d)ciclo-heten-5,10-imina ; 0,05mg/Kg (MK-801; 0,05 mg/Kg) 24 horas antes do teste não alterou o comportamento dos animais. Quando a cetamina foi administrada diretamente na MCPD (matéria cinzenta periaquedutal dorsal) observou-se que apenas a dose mais baixa, de 2µg, facilitou a fuga 1, o que caracteriza um efeito tipo-panicogênico rápido. Além disso, nenhum dos esquemas de administração e doses empregados alteraram a atividade locomotora dos animais no campo aberto. Para investigar o envolvimento da via de sinalização de BDNF/TrκB nos efeitos da cetamina e do MK-801 na ansiedade no LTE, foi realizado a quantificação de TrκB total e fosforilado nos resíduos 706/707 e 515 de tirosina (Y-706/707 e Y-515) da MCP de ratos. A cetamina 80mg/Kg e o MK-801 0,05 mg/Kg administrados agudamente antes da coleta da MCP, não induziram alteração estatisticamente significante na quantidade de pTrκB nos resíduos Y-706/707 e Y-515. Adicionalmente, a cetamina 10 e 80 mg/Kg, administrada aproximadamente 24 horas antes da coleta da MCP, não induziu alteração estatisticamente significante na quantidade de pTrκB no resíduo Y-706/707 e Y-515. Em conclusão, os resultados encontrados mostraram que a cetamina pode ter um efeito muito discreto no pânico, sendo que esse efeito depende tanto da dose quanto do esquema de administração. Ainda, pelo menos o efeito panicogênico da cetamina parece envolver a MCPD

Advancing understanding of deep convection microphysics via mesoscale modeling studies of well-observed case studies requires observation-based aerosol inputs. Here, we derive hygroscopic aerosol size distribution input profiles from ground-based and airborne measurements for six convection case studies observed during the Midlatitude Continental Convective Cloud Experiment (MC3E) over Oklahoma. We demonstrate use of an input profile in simulations of the only well-observed case study that produced extensive stratiform outflow on 20 May 2011. At well-sampled elevations between -11 and -23 degrees C over widespread stratiform rain, ice crystal number concentrations are consistently dominated by a single mode near similar to 400 mu m in randomly oriented maximum dimension (D-max). The ice mass at -23 degrees C is primarily in a closely collocated mode, whereas a mass mode near D-max similar to 1000 mu m becomes dominant with decreasing elevation to the -11 degrees C level, consistent with possible aggregation during sedimentation. However, simulations with and without observation-based aerosol inputs systematically overpredict mass peak D-max by a factor of 3-5 and under-predict ice number concentration by a factor of 4-10. Previously reported simulations with both two-moment and sizeresolved microphysics have shown biases of a similar nature. The observed ice properties are notably similar to those reported from recent tropical measurements. Based on several lines of evidence, we speculate that updraft microphysical pathways determining outflow properties in the 20 May case are similar to a tropical regime, likely associated with warm-temperature ice multiplication that is not well understood or well represented in models.

Doctor of Philosophy
Department of Chemistry
Christine M. Aikens
Gold and silver particles with dimensions less than a nanometer possess unique characteristics and properties that are different from the properties of the bulk. They demonstrate a non–zero HOMO–LUMO gap that can reach up to 3.0 eV. These differences arise from size quantization effects in the metal core due to the small number of atoms. These nanoparticles have attracted great interest for decades both in fundamental and applied research. Small gold clusters protected by various types of ligands are of interest because ligands allow obtaining gold nanoclusters with given sizes, shapes and properties. Three main families of organic ligands are usually used for stabilization of gold nanoclusters: phosphine ligands, thiolate ligands and DNA. Usually, optical properties of these NPs are studied using optical absorption spectroscopy. Unfortunately, sometimes this type of spectrum is poorly resolved and tends to appear very similar for different complexes. In these cases, circular dichroism (CD) and magnetic circular dichroism (MCD) spectroscopy can be applied. However, the interpretation of experimental CD and MCD spectra is a complicated process. In this thesis, theoretically simulated CD and MCD spectra were combined with optical absorption spectra to study optical activity for octa– and nona– and undecanuclear gold clusters protected by mono– and bidentate phosphine ligands. Additionally, optical properties of bare and DNA protected silver NPs were studied. Theoretical CD spectra were examined to learn more about the origin of chirality in chiral organometallic complexes, and to contribute to the understanding of the difference in chiroptical activity of gold clusters stabilized by different phosphine ligands and DNA–stabilized silver clusters. Furthermore, optical properties of the small centered gold clusters Au₈(PPh₃)₈²⁺ and Au₉(PPh₃)₈³⁺ were examined by optical absorption and MCD spectra using TDDFT. Theoretical MCD spectra were also used to identify the plasmonic behavior of silver nanoparticles. These results showed that CD and MCD spectroscopy yield more detailed information about optical properties and electronic structure of the different chemical systems than optical absorption spectroscopy alone. Theoretical simulation of the CD and MCD spectra together with optical absorption spectra can be used to assist in the understanding of empirically measured CD and MCD and provide useful information about optical properties and electronic structure.

Mestrado em Biotecnologia - Biotecnologia Alimentar
O presente trabalho descreve as atividades desenvolvidas durante o estágio curricular efetuado na empresa Dan Cake (Portugal), S.A., no âmbito do mestrado em Biotecnologia Alimentar. Em maio de 2016, o Painel de Contaminantes da Cadeia Alimentar da Autoridade Europeia para a Segurança Alimentar (EFSA) publicou uma opinião científica sobre os riscos para a saúde pública relacionados com a presença do 3-monocloropropano1,2-diol (3-MCPD), os seus ésteres de ácidos gordos e os ésteres glicidílicos (GE) nos alimentos. Estes são considerados genotóxicos e carcinogénicos, isto significa que ao longo do tempo podem danificar o DNA e causar cancro. Posto isto, a dose diária admissível (DDA) para o 3-MCPD e os seus ésteres foi reduzida de 2 μg/kg de peso corporal para 0,8 μg/kg de peso corporal. Um cliente Alemão exige que os produtos para ele vendidos apresentem metade da DDA surgindo, assim, a necessidade de acompanhar a empresa no estudo deste contaminante, para a nova formulação dos produtos, de forma a analisar o que pode ser feito por parte da mesma para mitigar os valores deste contaminante no produto final. Para melhor compreender o contaminante foram realizadas análises ao pão e às tostas da nova formulação das tostas com recurso a um laboratório externo. Foram também analisadas as matérias-primas utilizadas na formulação que condicionam o teor de 3-MCPD, o óleo de palma e o desmoldante, com recurso à técnica de infravermelho. As análises realizadas em laboratório externo permitiram perceber que poderá ocorrer um aumento de 3-MCPD durante o processo de tostagem e que o desmoldante poderá ter influência no teor do contaminante. Já a técnica de FT-IR não parece ser a técnica indicada para analisar este contaminante, contudo forneceu dados importantes a nível nutricional das tostas analisadas. Com os resultados das análises externas foram ainda conseguidos dados interessantes para futuras pesquisas. Além da investigação, o estágio integrou-se, na maior parte do tempo, em atividades desenvolvidas nos Departamentos de Rotulagem, através da prestação de informação aos consumidores sobre géneros alimentícios, e no Departamento de Segurança e Qualidade Alimentar, realização de inspeções mensais às linhas de produção.
The present work describes the activities developed during the curricular internship at the company Dan Cake (Portugal), S.A., within the scope of the Master's Degree in Food Biotechnology. In May 2016 the European Food Safety Authority (EFSA) Panel on Contaminants in the Food Chain published a scientific opinion on the public health risks associated with the presence of 3-monochloropropane-1,2-diol (3-MCPDs), their fatty acid esters and the glycidyl esters (GE) in food. These are considered genotoxic and carcinogenic, this means that over time they can damage the DNA and cause cancer. Thereafter, the allowable daily intake (DDA) for 3-MCPD and its esters was reduced from 2 μg / kg body weight to 0.8 μg / kg body weight. One of the company’s clients demands that the products sold to them present half of the TDI therefore, the need arose to follow the company in a study for this contaminant in order to analyze what could be done by the same to mitigate the values of this contaminant in the final product. To understand the contaminant better, analyzes were carried out on a recipe of sold toasts using analyzes in an external laboratory and analyzes of the raw materials at risk using the FT-IR technique in order to assist the company in the acquisition of knowledge. The analysis carried out in an external laboratory showed that an increase of 3-MCPD may occur during the roasting process and that the release agent may influence the contaminant content. The FT-IR technique does not seem to be the indicated technique to analyze this contaminant; however, it provided important nutritional data of the analyzed toasts. With the results of the external analyzes, interesting data were also obtained for future research. In addition to this investigation. the internship had most of the time the direct contact with activities developed in the Departments of Labeling and Security and Food Quality.

Esta investigación examinó el uso de rúbricas de ensamblaje, describiendo su evolución a partir de rúbricas de piezas, y estudió cómo afectan a la autoevaluación de los estudiantes. También se valoró la evaluación de los estudiantes por los instructores, encontrando que, mientras que las rúbricas de ensamblaje fueron parcialmente comprendidas y utilizadas de manera eficiente por los estudiantes, éstas fueron usadas con más éxito por los instructores. En esta investigación se han abordado estrategias diseñadas para mejorar la comunicación de la intención de diseño en modelos CAD, acrecentando así su calidad, con directrices dirigidas a evaluar su eficiencia. Es evidente que se necesitan métricas dirigidas hacia la instrucción de la intención de diseño, ya que la intención de diseño transferida a través de modelos CAD puede realizarse en tres etapas con criterios contradictorios que deben ser equilibrados para llegar a la mejor estrategia de modelado. La investigación ha incluido el desarrollo de un método de validación que demuestra que las rúbricas son dispositivos útiles para garantizar una comunicación consistente de la intención de diseño, y son fundamentales no sólo para evaluar, sino también para comunicar las expectativas del instructor. En esta investigación se examinó cómo definir claramente las cualidades de la intención de diseño para permitir una más fácil evaluación de un ensamblaje CAD. Para todas las dimensiones de la rúbrica, se encontró más concordancia y correlación entre instructores que entre instructores y estudiantes. Existe una correlación moderada/fuerte entre los instructores para las dimensiones de la validez, completitud, concisión y claridad, mientras que existe una ligera correlación para las dimensiones de consistencia e intención del diseño. En segundo lugar, las rúbricas también pueden ser descritas como estáticas o dinámicas. Las rúbricas estáticas, existen sólo en papel, no proporcionan retroalimentación inmediata al educando. Las rúbricas dinámicas realizan cálculos que proporcionan observaciones de evaluación inmediatas al usuario. Además, pueden adaptarse a situaciones específicas dependiendo de la capacidad del usuario. Las rúbricas electrónicas son ideales para rúbricas dinámicas, y permiten el uso y desarrollo de rúbricas adaptativas y adaptables, como se describe a continuación. En tercer lugar, las rúbricas deben ser adaptables lo que debería hacerlas fácilmente comprensibles y fáciles de usar, y adaptativas. Las rúbricas de evaluación se usan cuando un experto determina el progreso pedagógico de un educando, mientras que las rúbricas formativas son empleadas por los propios estudiantes, para trazar su progreso e identificar las deficiencias escolares para las que necesitan apoyo. Las rúbricas se deben refinar y mejorar de forma continuada, en un proceso iterativo y colaborativo, hasta que se alcance un acuerdo satisfactorio, tanto entre evaluadores como entre evaluadores y alumnos. Por ello, se desarrollaron mapas de aserciones que ilustran el modo en que la estrategia de expansión-contracción adapta las rúbricas al progreso del aprendiz de CAD, a la vez que ayudan a comprender las diferentes dimensiones de la rúbrica. Basándose en los experimentos con las rúbricas de ensamblajes, es evidente que las pequeñas diferencias entre los instructores sugieren que la rúbrica de ensamblajes propuesta es lo suficientemente sofisticada como para proporcionar una evaluación acumulativa imparcial del desempeño del alumno. En consecuencia, se puede afirmar con confianza que los evaluadores pueden usarse indistintamente sin sacrificar la precisión. Sin embargo, la rúbrica de ensamblaje posee una eficacia finita para producir una autoevaluación formativa de las habilidades de ensamblaje CAD para nuevos alumnos.
This research examined the use of assembly rubrics, described how they evolved from parts rubrics, and studied how they affect student self-evaluation. Instructor assessment of students was also evaluated, finding that while the assembly rubrics were partially understood and effectively used by the students, they were more successfully utilized by the instructors. Strategies designed to improve design intent communication in CAD models, in order to enhance their quality, with guidelines targeted to evaluate efficiency, have been addressed with this research. It is apparent that metrics directed toward the instruction of design intent are needed, since design intent transferred through CAD models can be performed at three stages with competing tradeoffs that must be balanced to arrive at the best modeling strategy. Research included the development of a validation approach that reflects that rubrics are valuable devices to expedite consistent design intent communication, and are vital not only for evaluation, but also for the communication of instructor expectations. This research examined how to clearly define qualities of design intent to enable easier CAD assembly assessment. It has been found that there is more inter-rater agreement and correlation between instructors than between instructors and students, for all rubric dimensions. There is strong to moderate correlation between instructors for the dimensions of validity, completeness, conciseness, and clarity, while slight correlation exists for the dimensions of consistency and design intent. Secondly, rubrics can also be described as being either static or dynamic. Static rubrics, existing in paper form only, do not provide immediate feedback to the learner. Dynamic rubrics perform calculations that provide immediate evaluative observations to the user. Besides, they can be independently adapted to specific situations depending on the capability of the user. Electronic rubrics are ideally suited for dynamic rubrics, and permit the use and development of both adaptable and adaptive rubrics, as described next. Thirdly, rubrics need to be adaptable which should make them easily understood and user-friendly, and adaptive (rubric can change itself, depending on the usage pattern). Evaluative rubrics are used when an expert determines the pedagogical progress of a learner, while formative rubrics are employed by the learners themselves, in order to chart their progress and identify scholastic deficiencies that are in need of remediation. Rubrics must be continually refined and improved, in an iterative, collaborative process, until satisfactory agreement is attained, both between raters, but also between raters and learners. Thus, assertions maps were developed, illustrating how the expand-contract strategy adapts the rubrics to CAD trainee progress, while assisting the understanding of the different rubric dimensions. Based on the assembly rubric experiments, it is apparent that the small differences between instructors suggests that the proposed assemblies rubric is sufficiently sophisticated to furnish an unbiased accumulative assessment of student performance. Accordingly, it can be confidently stated that raters can be used interchangeably without sacrificing accuracy. However, the assembly rubric possesses finite efficacy to produce formative self-evaluation of CAD assembly skills for new learners.
Aquesta investigació examinà l'ús de rúbriques de acoblament, descrivint la seua evolució a partir de rúbriques de peces, i estudià cóm afecten a la autoavaluació dels estudiants. També es va valorar la avaluació dels estudiants per els instructors, trobant que, mentre que les rúbriques de acoblament van ser parcialment compreses i fetes servir de manera eficient per els estudiants, van ser usades amb mes èxit per els instructors. En aquesta investigació s'han abordat estrategues dissenyades per a millorar la comunicació de la intenció de disseny en models CAD, creixentat així la seua qualitat, amb directrius dirigides a avaluar la seua eficiència. Es evident que es necessiten mètriques dirigides cap a la instrucció de la intenció de disseny, ja que la intenció de disseny transferida a través de models CAD pot realitzar-se en tres etapes amb criteris contradictoris que deuen ser equilibrats per a arribar a la millor estratègia de modelatge. La investigació ha inclòs el desenvolupament de un mètode de validació que demostra que las rúbriques son dispositius útils per a garantir una comunicació consistent de la intenció de disseny, i son fonamentals no només per a avaluar, però també per a comunicar les expectatives de l'instructor. En aquesta investigació s'examinà com definir clarament les qualitats de la intenció de disseny per a permetre una mes fàcil avaluació de un acoblament CAD. Per a totes les dimensions de la rúbrica, es va trobar mes concordança i correlació entre instructors que no pas entre instructors i estudiants. Existeix una correlació moderada/fort entre els instructors per a les dimensions de la validesa, completesa, concisió i claredat, mentre que existeix una lleugera correlació per a les dimensions de consistència i intenció del disseny. En segon lloc, les rúbriques també poden ser descrites com estàtiques o dinàmiques. Les rúbriques estàtiques, existeixen sòls en paper, no proporcionen retroalimentació immediata a l'educand. Les rúbriques dinàmiques realitzen càlculs que proporcionen observacions de avaluació immediates al usuari. A mes, poden adaptar-se a situacions específiques dependent de la capacitat de l'usuari. Les rúbriques electròniques son ideals per a rúbriques dinàmiques, i permeten l'ús i desenvolupament de rúbriques adaptatives i adaptables, como es descriu a continuació. En tercer lloc, les rúbriques deuen ser adaptables, el que deuria ferles fàcilment comprensibles i fàcils d'usar, i adaptatives. Les rúbriques d'avaluació se usen quant un expert determina el progrés pedagògic de un educand, mentre que les rúbriques formatives son fetes servir per els propis estudiants, per a traçar el seu progrés i identificar les deficiències escolars para a les que necessiten suport. Les rúbriques es deuen refinar i millorar de forma continuada, en un procés iteratiu i col·laboratori, fins que se arriba a un acord satisfactori, tant entre avaluadors como entre avaluadors i alumnes. Por això, es desenvoluparen mapes de assercions que il·lustren el mode en que la estratègia de expansió-contracció adapta les rúbriques al progres del aprenent de CAD, a la vegada que ajuden a comprendre les diferents dimensions de la rúbrica. Basant-se en els experiments amb les rúbriques de acoblaments, es evident que les xicotetes diferencies entre els instructors suggereixen que la rúbrica de acoblaments proposta es lo suficientment sofisticada com per a proporcionar una avaluació acumulativa imparcial del acompliment de l'alumne. En conseqüència, es pot afirmar amb confiança que els avaluadors poden usar-se indistintament sense sacrificar la precisió. No obstant, la rúbrica de acoblaments posseeix una eficàcia finita per a produir una autoavaluació formativa de les habilitats de acoblament CAD per a nous alumnes.
Otey, JM. (2017). A Contribution to Conveying Quality Criteria in Mechanical CAD Models and Assemblies through Rubrics and Comprehensive Design Intent Quantification [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/94627
TESIS

Cloropropanóis são um grupo conhecido de contaminantes relacionados ao processamento de alimentos. Eles são formados na reação entre lipídeos e cloretos quando submetidos ao tratamento térmico, e podem ser encontrados na forma livre ou ligada. O 3-monocloro-1,2-propanediol (3-MCPD), é classificado pela IARC como possível carcinógeno humano (grupo 2B). O glicidol (e seus ésteres), é classificado também pela IARC como uma substância provavelmente carcinogênica para seres humanos (grupo 2A), e, recentemente, vem sendo encontrado em alimentos. O objetivo deste trabalho foi avaliar a presença do 3-MCPD e do glicidol em óleos vegetais comestíveis utilizando a cromatografia gasosa com detector de massa triplo quadrupolo MS/MS. A técnica utilizada foi a preconizada pela AOCS Cd 29c-13, sendo uma análise indireta, e foi possível adaptá-la visando as determinações do 3-MCPD e glicidol através da construção de curvas de calibração e análises de amostras de referência. O método foi validado e os resultados indicaram o limite de detecção do composto 3-MCPD, de 42,4 µg/kg e o limite de quantificação de 50 µg/kg, e para o Glicidol indicaram o limite de detecção de 43,5 µg/kg e limite de quantificação de 50 µg/kg. Os resultados para 3-MCPD obtidos nos ensaios da curva de calibração e linearidade demonstraram que o método foi capaz de expressar resultados com boa linearidade (0 - 10 mg/kg , r2, = 0.9991). Os resultados obtidos nos ensaios de exatidão obedeceram aos critérios de 70 a 120% de recuperação, e ±20% de variação entre os resultados de acordo com SANTE (2017). O método em questão demonstrou ser seletivo, uma vez que não foram observados picos interferentes nos tempos de retenção dos compostos estudados. Os ensaios de precisão nos níveis baixos, médio e alto e robustez demonstraram que o método é robusto e preciso, portanto a validação foi considerada adequada ao uso pretendido. Foram analisadas 368 amostras de óleos vegetais (76 amostras de óleo de canola, 48 amostras de óleo de milho, 69 amostras de óleo de algodão, 33 amostras de óleo de palma, 10 amostras de óleo de palmiste, 50 amostras de oleína de palma, 30 amostras de óleo de soja e 51 amostras de óleo de girassol). As concentrações das amostras analisadas apresentaram resultados para 3-MCPD com valores médios entre 203 a 1205 µg/kg. Para o Glicidol os valores foram de 2 a 1198 µg/kg, com elevado o desvio padrão entre os resultados analíticos, onde o óleo de palma apresentou a maior variação de 1600 a 5260 µg/kg. Através da avaliação do risco realizada para o composto 3-MCPD foi possível detectar, utilizando o critério do pior cenário de exposição e resultados analíticos, os valores diários de consumo de óleo de algodão de 0,044 µg/kg p.c., de óleo de girassol 0,045 µg/kg p.c., óleo de canola 0,18 µg/kg p.c., óleo de palma de 0,28 µg/p.c, óleo de milho de 0,0462 µg/kg p.c., e o óleo de soja, de maior consumo no Brasil (72%) apresentou o valor de 0,27 µg/kg p.c. O consumo de todos estes óleos, pela a população brasileira, pode ser considerado seguro ao comparar com o valor de TDI Ingestão Diária Tolerável - de 2µg/kg p.c.. Através da avaliação do risco realizada também utilizando o critério de pior cenário de exposição e e resultados analíticos para o composto glicidol foi possível verificar que os valores diários de consumo de óleo de algodão de 0,061 µg/kg p.c., de óleo de girassol 0,03 µg/kg p.c., óleo de canola 0,13 µg/kg p.c. e de óleo de palma de 0,57 µg/p.c, de óleo de milho de 0,11 µg/kg p.c, e o óleo de soja de maior consumo no Brasil (72%) não ultrapassam o valor de 0,288 µg/kg p.c indicando consumo seguro destes óleos para a população brasileira baseado na TDI de 1000µg/kg p.c.
Chloropropanols are a known group of contaminants related to food processing. They are formed during the reaction process between lipids and chlorides when submitted to heat treatment and can be found in free or bound form. The 3-monochloro-1,2-propanediol (3-MCPD), is classified by IARC as a possible human carcinogen (group 2B). Glycidol (and its esters), also classified by IARC as a substance likely to be carcinogenic to humans (group 2A), has recently been found in food. The present study aims to evaluate the presence of 3-MCPD and glycidol in edible vegetable oils using gas chromatography with triple quadrupole MS/MS mass detector. The technique applied is recommended by AOCS, guide Cd 29c-13, an indirect analysis, and allows quantification of 3-MCPD and glycidol by building the calibration curves and analysis of reference samples. The method was validated and the detection limit of the contaminant 3-MCPD of 42,4 µg/kg and the quantification limit of 50 µg/kg was established. For Glycidol the detection limit of was 43,5 µg/kg and quantification limit was 50 µg/kg. The results obtained in the calibration and linearity curves demonstrated that the method could express results with good linearity (0 10 mg/kg, r2, = 0.9991). The results obtained in the trueness trials agreed to the criteria of 70 to 120% of recovery, and ± 20% of variation between the results according to what is preconized by SANTE (2017). The method showed to be selective, since no interfering peaks were observed in the retention times of the studied compounds. The tests performed on low, medium and high values demonstrated the robustness and precision of the method, so the validation was considered completed and suitable for the purpose. A total of 368 vegetable oil samples were analyzed (76 samples of canola oil, 48 samples of corn oil, 69 samples of cottonseed oil, 33 samples of palm oil, 10 samples of kern palm oil, 50 samples of palm olein, 30 samples of soybean oil and 51 samples of sunflower oil). The results found in samples for 3-MCPD were within mean values between 203 and 1205 µg/kg. The results found in samples for glycidol were within mean values between 2 to 1198 µg/kg where palm oil presented the highest variation for glycidol from 1600 to 5260 µg/kg. Through the risk assessment for the contaminant 3-MCPD it was possible to detect the values based on exposed worst case scenario and analytical results. The results for cottom oil were 0,044 µg/kg bw, sunflower 0,045 µg/kg bw, canola 0,18 µg/kg bw and palm oil 0,28 µg/kg bw, corn oil 0,0462 µg/kg bw, and for soybean, which is the most consumed oil in Brazil (72%) the value of 0,27 µg/kg bw. These results indicates safe consumption for these oils based in the Theoretical Daily Ingestion - TDI of 2µg/kg bw. The risk assessment for the glycidol based on exposure worst case scenario and analytical results presented for cottom oil the value of 0,061 µg/kg bw, sunflower 0,03 µg/kg bw, canola oil 0,13 µg/kg bw , palm oil 0,57 µg/kg bw, corn oil 0,11 µg/kg bw and for soybean, which is the most consumed in Brazil - 72% the value of 0,27 µg/kg bw. These results indicates safe consumption for these oils based in the TDI of 1000µg/kg bw.

Recent technological advances in computer science have contributed to immense data generation in many critical areas of biology. These data can be used in intelligent information systems to better understand biological processes from the atomic details of biological molecules to the interaction of species in an ecosystem. This thesis presents My Crystal Diary (MCD), an integrated software application designed for use in an intelligent decision-support system for planning novel crystallisation experiments. PostgreSQL database server is the information repository containing both the experimental data and general knowledge. Web-based interfaces developed in Plone provide remote access to the database by utilizing a Zope Web application server.

The Mediterranean Commission on Sustainable Development (MCSD) is established as an advisory body within the Mediterranean Action Plan (MAP) framework, in order to provide advice on programs and prepare recommendations for the Contracting Parties. The MCSD identifies and evaluates major economic, environmental and social problems specified in Agenda MED 21. It aims to track the implementation of the proposals it submits to the Contracting Parties. Furthermore, the MCSD is open to participation from the main groups of the society, which have equal footing alongside government representatives. Within the limits imposed upon it, the MCSD provides a regional forum for dialogue and a promising framework for defining a regional sustainable development strategy in the Mediterranean. Its regional nature and its composition constitute an innovative contribution to promote the integration of environmental concerns in development policies. The object of this study is to evaluate the work that has been carried out by MCSD and understand the complex structure of an institution through which international and regional cooperation and coordination is achieved.

Die Regulation der Nahrungsaufnahme erfolgt zentral im Hypothalamus wo eine Vielzahl von G-Protein-gekoppelten Rezeptoren exprimiert werden die an der Gewichtsregulation beteiligt sind. Periphere hormonelle Signale aktivieren ihre korrespondierenden Rezeptoren im Nucleus arcuatus (ARC) oder im Nucleus paraventricularis (PVN) und modifizieren dadurch sowohl das anorexigene System, z.B. über die Stimulation des Melanocortin-4-Rezeptors (MC4R) im PVN, als auch das orexigene System mit dem Neuropeptide Y (NPY) sowie dem Agouti-related Protein (AgRP). Im Zuge einer systematischen Interaktionsstudie wurden verschiedene GPCRs, die entweder mit dem MC3R oder dem MC4R auf dem gleichen Neuron koexprimiert werden und nachweißlich die Appetit- und Gewichtregulation beeinflussen, untersucht. Basierend auf den Ergebnissen von Sandwich-ELISA und FRET- (Fluoreszenz-Energie-Transfer)Studien konnte eine Interaktion des MC3R mit dem Growth hormone secretagogues Rezeptor (GHSR) bestimmt werden, die beide auf den NPY/AgRP-Neuronen des ARC lokalisiert sind. Der MC3R gehört zu den Gαs bindenden Rezeptoren wohingegen GHSR über den Gαq vermittelten Signaltransduktionsweg signalisiert. Es konnte eine Erhöhung der induzierten cAMP-Spiegel infolge der Stimulation des MC3R sowohl mit α-, als auch β- und γ-MSH für die Koexpression von MC3R mit GHSR im Vergleich zum MC3R Homodimer ermittelt werden. Die Charakterisierung des neuen Signalisierungsverhaltens des Heterodimers unter der Verwendung verschiedener Inhibitoren zeigte eine Aktivierung von Gαi in Gegenwart der endogenen Agonisten beider Rezeptoren. Die Beobachtung unterschiedlicher Regulationsmuster nach der Kostimulation des Heterodimers in Abhängigkeit von α- oder γ-MSH jeweils in Anwesenheit von Ghrelin verweist auf komplexe Interaktionsmechanismen zwischen dem Melanocortin- und dem Ghrelin-Rezeptor innerhalb der hypothalamischen Gewichtsregulation.
Food intake is centrally regulated in hypothalamic nuclei where many GPCRs are expressed which are known to be involved in weight regulation.Peripheral hormonal signals activate their corresponding receptors in the arcuate nucleus (ARC) or paraventricular nucleus (PVN) and modulate the orexigenic (appetite-supressing) pathway mediated by stimulation of the melanocortin-4-receptor (MC4R) as well as the anorexigenic (appetite-stimulating) pathway including neuropeptide Y (NPY) and agouti-related protein (AgRP). In a systematic approach we investigated the interaction of a selective number of GPCRs which are co-expressed on the same neurons like MC3R or MC4R and know to play an essential role in hypothalamic weight regulation. Based on the results of a sandwich ELISA and fluorescence resonance energy transfer (FRET) approach we report the interaction of the MC3R and the growth hormone secretagogue receptor (GHSR) which are co-expressed on arcuate NPY/AgRP neurons. It is known that MC3R couple to the Gαs whereas GHSR couple to the Gαq signaling pathway. However, here the co-expression of MC3R and GHSR reveal a profoundly increase cAMP-accumulation after melanocortin (α-, β- and γ-MSH) challenge, that is higher compared to MC3R activation alone. In-depth characterization of the new signaling properties of the MC3R/GHSR heterodimer by different inhibitors revealed the activation of Gαi in the presents of both endogene agonists. The observation of different regulatory pattern after co-stimulation of the heterodimer depending on the endogenouse ligands (α- or γ-MSH) of MC3R reflect complex functional interaction mechanisms between melanocortin and ghrelin receptors within the hypothalamic signaling pathways of weight regulation.