Considerando a importância crescente das técnicas termoanalíticas na indústria e na pesquisa contemporânea, torna-se necessário apresentá-las de forma adequada aos alunos de cursos de graduação, não apenas de química, mas de ciência dos materiais, física, farmácia, das diversas modalidades de engenharia, entre outros. Por outro lado, pode-se notar que isso raramente acontece, por diversos motivos, como falta de equipamentos, falta de experimentos demonstrativos das técnicas e até mesmo de falta de preparo dos docentes, com relação ao conhecimento dos fundamentos das técnicas e normalização de nomenclatura. No sentido de contribuir com o ensino de Análise Térmica em nosso país, este trabalho teve por objetivo buscar informações históricas e compilar e/ou desenvolver experimentos didáticos que possam ser usados na demonstração de conceitos teóricos e aspectos práticos das técnicas termoanalíticas mais usadas no Brasil, como a Termogravimetria (TGA), Termogravimetria Derivada (DTG), Análise Térmica Diferencial (DTA) e Calorimetria Exploratória Diferencial (DSC). Para avaliar o efeito didático do material desenvolvido foi proposto um curso extracurricular no tema Análise Térmica, chamado \"Princípios e Aplicações de Análise Térmica\", em nível de graduação na forma de curso de Difusão Cultural, apoiado pela Pró-Reitoria de Cultura e Extensão da Universidade de São Paulo (USP). Participaram 12 alunos de graduação e 3 alunos de pós-graduação, estes últimos como ouvintes. Os participantes receberam material didático escrito, na forma de uma apostila, instruções teóricas e aulas práticas, envolvendo experimentos com problemas práticos contextualizados, em Análise Térmica. A avaliação do curso foi feita com base em questionários sobre expectativas dos alunos em relação ao curso, seus conhecimentos prévios e aqueles obtidos ao final do curso. Os questionários foram aplicados antes e após as atividades. A avaliação de conteúdo foi feita usando questões sobre o tópico abordado e revelou significativo ganho de conhecimento desses alunos em relação às técnicas termoanalíticas. Assim, atingiu-se o esperado, contribuindo de alguma maneira para o ensino de Análise Térmica e sua aplicação nos cursos de graduação, envolvendo Termogravimetria, Termogravimetria Derivada, Análise Térmica Diferencial e Calorimetria Exploratória Diferencial. / Considering the increasing relevance of the thermoanalytical techniques in both industry and contemporary research, it becomes interesting to present such techniques in a proper way to undergraduate students, not only in chemistry, but also in materials science, physics, pharmacy, the several areas of engineering, and other potential users of these techniques. Moreover it can be noted that this rarely happens due to many reasons such as unavailability of equipments, to demonstrate the experimental details and even lacking in knowledge of professors regarding the fundamentals of the techniques and standardization in nomenclature. In order to contribute to the Thermal Analysis education in Brazil, this study aimed to seek historical information and compilation and/or development of didactic experiments that can be used in the demonstration of theoretical concepts and practical aspects of the most commonly used thermoanalytical techniques, such as Thermogravimetry (TGA), Derivative Thermogravimetry (DTG), Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC). Beyond that, it was necessary to apply these contents with undergraduate volunteer students. Therefore, an extracurricular Thermal Analysis course in this subject, named \"Principles and Applications of Thermal Analysis\", supported by the Dean of Culture of the Universidade de São Paulo (USP) was offered. Twelve undergraduate and three graduate students from four Universities of São Paulo State attended the course. These students received educational written materials in the form of a handout, instructions in theoretical aspects and practical sessions involving experiments, represented by practical problems in Thermal Analysis. The course evaluation was based on questionnaires about students\' expectations and their previous knowledge and that obtained by the end of the activity. The scope evaluation was made using questions about the topics covered and revealed significant improvement in the knowledge of the students regarding the thermoanalytical techniques covered in the course. Thus the expectations of the dissertation have been satisfied in developing a written material for thermal analysis education covering historical aspects as well as, theoretical and practical concepts of Thermogravimetry, Differential Thermal Analysis, Differential Thermal Analysis and Differential Scanning Calorimetry and their application to undergraduate courses.

O Grande Colisor de Hádrons (Large Hadron Collider - LHC) é um acelerador de prótons e íons pesados localizado no CERN (Conseil Européen pour la Recherche Nucléaire). Em um de seus experimentos, ALICE (A Large Ion Collider Experiment ), está sendo projetado um detector dedicado a explorar os aspectos únicos de colisões núcleo-núcleo. A principal finalidade do ALICE é estudar a formação de um novo estado da matéria, o plasma de quarks e glúon. Para isto devem-se ter medidas precisas de hádrons, elétrons, múons e fótons produzidos em colisões chumbo-chumbo. Assim está sendo proposto um calorímetro frontal (Foward Calorimeter - FoCal) como um upgrade para o ALICE. A função deste calorímetro é o estudo das funções de distribuição de pártons (Partons distribuction Functions - PDF) no regime de pequenos valores do x de Bjorken. Nesta região é esperado que estas PDFs tenham um comportamento não linear devido ao processo de saturação de glúons. Para o estudo desta região é necessária a medida de fótons diretos produzidos na colisão. Estes, por sua vez, ficam mascarados pelo fundo de fótons provenientes do decaimento de píon, o que leva a uma necessidade de suas identificações. Com isto surge a oportunidade para a utilização do método de clusterização que é uma ferramenta de mineração de dados. Este trabalho contribuiu para o desenvolvimento inicial de um algoritmo de clusterização para o calorímetro FoCal. / The Large Hadron Collider (LHC) is a CERN\'s accelerator that collides protons and heavy ions. One of its experiments, ALICE, is building a new detector to explore new aspects of heavy ions collisions. The Alice\'s main goal is to study the formation of quark-gluon plasma (QGP). To do that it\'s necessary to get accurate data on hadrons, electrons, muons and gammas created in lead-lead collision. So, to accomplish that a new calorimeter is in study to scan the foward region of experiment, the Foward Calorimeter (FoCal). It\'s proposed to study Parton Distribution Functions (PDFs) in a regime of very small Bjorken-x, where it is expected that the PDFs evolve non-linearly due to the high gluon densities, a phenomena referred to as gluon saturation.But to do that it\'s required to measure the direct gammas created on collision. These fotons are blended on by fotons descendant of pion. So there\'s a need to separate it from the direct gammas. One way to solve this problem is to use clustering methods (a type of mining data algorithm). This work helped on early stages of development that clustering algorithm.

INTRODUÇÃO: A doença de Gaucher (DG) é um erro inato do metabolismo, do grupo das doenças lisossômicas, causado pela atividade deficiente da enzima glicocerebrosidase. Os tipos mais comuns da DG são o tipo I, que é o mais freqüente e não apresenta comprometimento neurológico; o II, agudo e neuropático; e o III, subagudo e neuropático. Todos os tipos caracterizam-se pela heterogeneidade clínica, com manifestações sintomáticas e de intensidade distintas, tais como hepatoesplenomegalia, alterações ósseas e hematológicas. Alguns estudos descrevem alterações metabólicas como gasto energético basal (GEB) aumentado – hipermetabolismo - em pacientes sem tratamento. A terapia de escolha para a DG é a reposição enzimática (TRE), a qual consegue reverter muitas das manifestações da doença. OBJETIVOS: 1) Avaliar o GEB por meio de calorimetria indireta em pacientes com DG do Centro de Referência do Rio Grande do Sul; 2) Avaliar o estado nutricional dos pacientes incluídos no estudo; 3) Relacionar o GEB com as condições clínicas dos pacientes. METODOLOGIA: Estudo transversal, prospectivo, controlado. Os pacientes atendidos no CRDG foram convidados a participar do estudo (n= 29), sendo que 17 concordaram (média de idade= 30,0 ± 17,2 anos, sexo masculino= 8; DG tipo III= 3 pacientes). Os pacientes com DG tipo I (n= 14; sexo masculino= 6) foram pareados por sexo, idade e índice de massa corporal (IMC) com controles hígidos para avaliação do GEB. Para determinação dos valores de VO2 e VCO2 foi utilizado um ergoespirômetro (MedGraphics Cardiorespiratory Diagnostic Systems, modelo CPX-D). Os pacientes e os controles receberam orientação prévia quanto ao jejum e o repouso e no dia da calorimetria foram pesados e medidos, sendo então calculado o IMC. Os pacientes não apresentavam outras morbidades, nem estavam em uso de medicamentos que poderiam interferir no GEB. Nas análises estatísticas, foi utilizado o GEB em kcal/kg/dia. RESULTADOS: A avaliação do estado nutricional revelou que, no grupo dos pacientes com DG tipo I, cinco estavam com sobrepeso e os demais eutróficos; no grupo com DG tipo III, dois pacientes encontravam-se desnutridos e um eutrófico. Foram realizadas 19 avaliações do GEB em 17 pacientes: dois pacientes a realizaram no período pré e após 6 meses de TRE. A média de idade e de IMC dos pacientes com DG tipo I e dos controles foi de 32,8 ± 17,6 e 32,1 ± 16,6 anos e 23,3 ± 3,1 e 22,4 ± 3,1kg/m2, respectivamente. A idade dos pacientes com DG tipo III foi, respectivamente, 12, 17 e 20 anos. Quatorze pacientes estavam recebendo TRE (média de tempo de TRE= 6,6 ± 5,3 anos; média de dose de enzima= 27,1 ± 11,7 UI/kg/inf. de imiglucerase). A média de GEB dos pacientes com DG tipo I em TRE (n= 12) foi 27,1% maior do que a dos controles (p= 0,007). O GEB de pacientes em TRE (n=12) comparado aos sem TRE (n= 4) não apresentou diferença (p= 0,92). Comparando o GEB dos pacientes em TRE e o de seus controles com o GEB estimado pela equação de Harris-Benedict, observou-se que os pacientes apresentaram GEB 6,3% maior do que o estimado (p= 0,1), enquanto que seus controles tiveram GEB 17,0% menor do que o estimado (p= 0,001). O GEB medido dos pacientes com DG tipo III foi, respectivamente, 14%, 72% e 16% maior do que o estimado pela equação de Harris e Benedict. Não foi encontrada associação significativa entre GEB e as seguintes variáveis: idade, peso, estatura, escore de gravidade, quantidade de enzima recebida, idade de início de TRE, tempo de tratamento e presença ou ausência de megalias. A correlação do GEB com o IMC foi negativa e significativa, conforme esperado. DISCUSSÃO/CONCLUSÕES: O estado nutricional classificado pelo IMC mostrou que a maior parte dos pacientes com DG tipo I estava eutrófica; no entanto, um terço apresentou pré-obesidade. Dois dos três pacientes com DG tipo III encontravam-se desnutridos. Todos os pacientes, mesmo em TRE, apresentaram um GEB significativamente maior do que os controles. A TRE não consegue normalizar o hipermetabolismo desses pacientes. / INTRODUCTION: Gaucher disease (GD) is an inborn error of metabolism of the group of lysosomal diseases, caused by the deficient activity of the glucocerebrosidase enzyme. The most common types of GD are: type I, which is the most frequent and does not present neurological compromise; type II, which is acute and neuropathic; and type III, which is subacute and neuropathic. All types are characterized by clinical heterogeneity and symptomatic manifestations of various intensity, such as hepatoesplenomegaly and bone and hematological alterations. Some studies have described metabolic alterations, such as increased basal metabolic rate (BMR), that is, hypermetabolism, in untreated patients. The therapy of choice for GD is enzyme replacement therapy (ERT), which can stop many manifestations of the disease. OBJECTIVES: 1) To evaluate BMR by means of indirect calorimetry in patients with GD seen at the Reference Center for Gaucher Disease of Rio Grande do Sul (RCGD); 2) To evaluate the nutritional status of patients included in the study; 3) To relate BMR with clinical conditions presented by patients. METHODS: The present was a prospective, controlled, cross-over study. Patients seen at the RCGD were invited to participate in the study (n=29); of these, 17 agreed to participate (mean age=30.0 ± 17.2 years, male= 8; GD type III=3 patients). Patients with GD type I (n=14; male= 6) were paired by gender, age, and body mass index (BMI) to healthy controls to evaluate BMR. To determine the values of VO2 and VCO2 an ergospirometer was used (MedGraphics Cardiorespiratory Diagnostic Systems, model CPX-D). Patients and controls received previous orientation as to fasting and resting and, on the day of the calorimetry, were weighed and measured in order for the BMI to be calculated. Patients did not present any other morbidity, neither were they making use of any medication that could interfere with BMR. In the statistical analyses, BMR in kcal/kg/day was used. RESULTS: The evaluation of the nutritional status showed that, in the group of patients with GD type I, five patients were overweight; the other were eutrophic; in the group of patients with GD type III, two patients were malnourished; one was eutrophic. Nineteen evaluations of BMR were conducted in 17 patients; two patients conducted the evaluation in the period pre-ERT and after 6 months of ERT. Mean age and mean BMI of patients with GD type I and controls were 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1kg/m2, respectively. The age of patients with GD type III was, respectively, 12, 17 and 20 years. Fourteen patients were receiving ERT (mean time of ERT=6.6 ± 5.3 years; mean enzyme dose=27.1 ± 11.7 UI/kg/inf of imiglucerase). The mean BMR of patients with GD type I on TRE (n=12) was 27.1% higher when compared to controls (p=0.007). When compared to patients not on ERT (n=4), the BMR of patients on ERT (n=12) did not show any difference (p=0.92). Comparing the BMR of patients on ERT and that of their controls with the BMR estimated by the Harris-Benedict equation, we observed that patients showed a 6.3% higher BMR than the estimated (p=0.1), while the BMR of their controls was 17.0% lower than the estimated (p=0.001). The BMR of patients with GD type III was, respectively, 14%, 72% and 16% higher than the estimated by the Harris-Benedict equation. No significant association was found between BMR and the following variables: age; weight; height; severity score; amount of enzyme received; age at beginning of ERT; time of treatment; and presence or absence of megalies. The correlation between BMR and BMI was negative and significant, as expected. DISCUSSION/CONCLUSIONS: The nutritional status classified by BMI showed that most patients with GD type I were eutrophic; however, one third of the patients showed pre-obesity. Two of the three patients with GD type III were malnourished. All patients, even on ERT, showed a significantly higher BMR when compared to controls. In conclusion, ERT was not able to normalize the hypermetabolism of these patients.

Objetivos: Quantificar o gasto energético de crianças e adolescentes com bronquiolite obliterante pós-infecciosa acompanhados em ambulatório de pneumologia pediátrica e comparar com crianças e adolescentes hígidos. Metodologia: Estudo transversal com grupo controle incluindo 72 crianças e adolescentes de 8 a 18 anos. Comparou-se dois grupos de 36 indivíduos, um com diagnóstico de BO e outro hígido, os quais foram pareados pelo gênero, idade e classificação do IMC. Para avaliação nutricional utilizou-se a antropometria e a composição corporal. O gasto energético foi medido pela calorimetria indireta; o fator atividade pelo recordatório 24h de atividades físicas e a ingestão energética pelos inquéritos alimentares. Resultados: Os resultados a seguir são apresentados, respectivamente, para o grupo BO e para o grupo controle: idade (11,8 ± 2,7) e (12,3 ± 2,8); índice de massa corporal (18,9 ± 4,0 Kg/m2) e (18,8 ± 3,4 Kg/m2); gasto energético de repouso (GER) (1717,6 ± 781,5) e (2019,9 ± 819); gasto energético total (GET) (2677,5 ± 1514,0 Kcal/dia) e (3396,1 ± 1557,9Kcal/dia); estimativa da ingestão energética (2294,1 ± 746,7Kcal/dia) e (2116,5 ± 612,1Kcal/dia). O GER e GET não foram estatisticamente diferentes entre os grupos (p= 0,102; p=0,051). O GER não foi estatisticamente diferente nem quando ajustado para massa magra (p=0,116). O GER está associado a MM (r=0,490; p0,001), sendo que quanto maior a MM, maior o gasto energético. Não houve diferenças estatisticamente significativas entre o GET e o consumo energético no grupo BO (p=0,202). O grupo controle consumiu, em média, 1.279,6Kcal a menos do que o previsto pelo GET (p<0,001). Houve diferença estatisticamente significante entre o gasto energético medido pela calorimetria indireta e o estimado pelas fórmulas de predição. Todas as fórmulas de predição subestimaram a necessidade energética. Conclusão: O GER e o GET foram semelhantes entre os grupos. A estimativa da ingestão energética das crianças e adolescentes hígidos foi menor que o GET. Os resultados sugerem que todas as fórmulas de predição utilizadas subestimaram as necessidades energéticas quando comparadas com a calorimetria indireta. / Objectives: To quantify energy expenditure in children and adolescents with post-infectious obliterans bronchiolitis (OB) receiving outpatient pediatric pulmonology care and compare them with healthy children and adolescents. Methods: Cross-sectional study with control group including 72 children and adolescents aged 8-18 years. Two groups of 36 individuals were compared – one diagnosed with OB and another healthy – which were paired as to gender, age, and body mass index classification. Anthropometry and body composition were used for nutritional assessment. Energy expenditure was measured by indirect calorimetry, activity factor was assessed through 24-hour recall, and energy intake was measured by nutrition surveys. Results: The following results are respectively presented to the OB group and to the control group: age (11.8 ± 2.7) and (12.3 ± 2.8); body mass index (18.9 ± 4.0 Kg/m2) and (18.8 ± 3.4 Kg/m2); resting energy expenditure (REE) (1717.6 ± 781.5) and (2019.9 ± 819); total energy expenditure (TEE) (2677.5 ± 1514.0 Kcal/day) and (3396.1 ± 1557.9 Kcal/day); energy intake estimate (2294.1 ± 746.7 Kcal/day) and (2116.5 ± 612.1 Kcal/day). REE and TEE were not statistically different between groups (p=0.102; p=0.051). REE was not statistically different even when adjusted for lean mass (p=0.116). REE is associated with lean mass (r=0.490; p<0.001) – the higher the lean mass, the higher the energy expenditure. There were no statistically significant differences between TEE and energy expenditure in the OB group (p=0.202). The control group had an average intake 1279.6 Kcal lower than that predicted by TEE (p<0.001). There was a statistically significant difference between energy expenditure measured by indirect calorimetry and that estimated by prediction equations. All prediction equations underestimated energy needs. Conclusion: REE and TEE weresimilar between groups. Energy intake estimate in the healthy children and adolescents was lower than TEE. Results suggest that all prediction equations used in this study underestimated the energy needs when compared with indirect calorimetry.

Les références actuelles, pour les rayons X de moyenne énergie en radiothérapie, sont établies au LNHB en termes de kerma dans l’air. La dose absorbée dans l’eau, grandeur d’intérêt pour la radiothérapie, est déduite de ces valeurs par transfert conformément aux protocoles internationaux. Ce travail de thèse a permit d’établir les références en termes de dose absorbée dans l’eau dans les conditions de référence des protocoles en utilisant la méthode de calorimétrie dans l’eau. La calorimétrie est la mesure de la dose absorbée à partir de l’élévation de température. Un « calorimètre-eau » a été conçu et réalisé afin d’effectuer des mesures à 2 cm de profondeur : conditions de référence définies par le protocole AIEA TRS-398. Les débits de dose absorbée dans l’eau ainsi déterminés ont été comparés aux valeurs issues de l’application des protocoles fondés sur le kerma dans l’air. Un écart maximum inférieur à 2.1 % a été trouvé par rapport à la calorimétrie. L’incertitude type associée aux valeurs calorimétriques étant inférieure à 0.8 % et celle associée aux valeurs issues des protocoles étant de l’ordre de 3.0 %, les résultats sont compatibles aux incertitudes des méthodes près. Grâce à ces nouvelles références, la détermination de la dose absorbée dans l’eau dans ce type de faisceau pourra désormais être réalisée en appliquant le protocole AIEA TRS-398, conduisant ainsi à une forte réduction des incertitudes (facteur 3 par rapport au protocole AIEA TRS-277). Actuellement, aucun autre laboratoire primaire ne possède un tel instrument permettant l’établissement direct de ces références dans les conditions recommandées par les protocoles. / LNE-LNHB current references for medium energy X-rays are established in terms of air kerma. Absorbed dose to water, which is the quantity of interest for radiotherapy, is obtained by transfer dosimetric techniques following a methodology described in international protocols. The aim of the thesis is to establish standards in terms of absorbed dose to water in the reference protocol conditions by water calorimetry. The basic principle of water calorimetry is to measure the absorbed dose from the rise in temperature of water under irradiation. A calorimeter was developed to perform measurements at a 2 cm depth in water according to IAEA TRS-398 protocol for medium energy x-rays. Absorbed dose rates to water measured by calorimetry were compared to the values established using protocols based on references in terms of air kerma. A difference lower than 2.1% was reported. Standard uncertainty of water calorimetry being 0.8%, the one associated to the values from protocols being around 3.0%, results are consistent considering the uncertainties. Thanks to these new standards, it will be possible to use IAEA TRS-398 protocol to determine absorbed dose to water: a significant reduction of uncertainties is obtained (divided by 3 by comparison with the application of the IAEA TRS-277 protocol). Currently, none of the counterparts’ laboratories own such an instrument allowing direct determination of standards in the reference conditions recommended by the international radiotherapy protocols.

En tant que laboratoire national pour la métrologie des rayonnements ionisants, le Laboratoire National Henri Becquerel met au point les méthodes de mesures absolues pour établir les références dosimétriques. Il dispose, entre autres, de références dans des faisceaux de rayons X utilisés en radiothérapie et ayant une taille de champ comprise entre 10 et 2 cm de côté. Afin de s’approcher des plus petits champs utilisés en clinique, la miniaturisation des détecteurs absolus n’étant pas possible, il est proposé dans cette thèse de remplacer la dose absorbée en un point par le produit dose surface (PDS). L’applicabilité du PDS mesuré à l’aide de dosimètres dont la surface sensible est plus grande que celle du champ de rayonnement a été vérifiée. Ainsi, un calorimètre graphite avec une surface sensible de 3 cm de diamètre a été conçu, construit et testé. En vue du transfert des références dosimétriques à l’utilisateur, une chambre d’ionisation de même diamètre a elle aussi été réalisée et testée. Son coefficient d’étalonnage en termes de PDS a été déterminé dans des faisceaux circulaires de 2, 1 et 0.75 cm de diamètre avec une incertitude type inférieure à 0.7 %. La distribution relative de la dose absorbée dans l’eau en deux dimensions a été mesurée au moyen d’un dosimètre diamant, d’une chambre d’ionisation PinPoint et de films gafchromiques, pour lesquels un protocole de lecture spécifique a été mis au point. Les résultats dans le faisceau de 2 cm de diamètre ont montré un bon accord entre les approches en termes de PDS et de dose absorbée dans l’eau en un point, après application des facteurs de correction obtenus au moyen de simulations Monte Carlo et des mesures de distribution de dose. Les coefficients d’étalonnage de la chambre d’ionisation de grandes dimensions établis dans les champs de 1 et 0.75 cm de diamètre sont compatibles aux incertitudes près mais s’écartent de -2.6 % de celui établi dans le champ de 2 cm de diamètre. L’utilisation du PDS nécessite donc une surface de détection notablement plus grande que la section du mini-Faisceau. / The French primary standard dosimetry laboratory “Laboratoire National Henri Becquerel” is in charge of the establishment of dosimetric standards for ionizing radiation beams. Absolute dose measurements are thus available for X-Ray beams used in radiotherapy for field sizes between 10 and 2 cm. Since the miniaturization of absolute dosimeters is not possible for smaller field sizes, a dose area product (DAP) has been suggested as a substitute to the absorbed dose at a point.In order to measure a DAP with dosimeters which sensitive surface is larger than the beam, a graphite calorimeter with a sensitive surface of 3 cm diameter was designed, built and tested. An ionization chamber with the same diameter was realized and tested to transfer the dosimetric references to the end users. Its calibration factor in terms of DAP was determined in circular beams of 2, 1 and 0.75 cm diameter with an uncertainty smaller than 0.7 %. The two-Dimension relative dose distribution was measured thanks to a diamond dosimeter, a PinPoint ionization chamber and gafchromic films, using a specific protocol.Both approaches, respectively based on a PDS and an absorbed dose to water at a point, were in good agreement in the 2 cm beam. Correction factors determined from Monte Carlo simulations and measured dose distributions were needed for this comparison. The calibration factor of the large ionization chamber in the 1 and 0.75 cm diameter beams were in good agreement within the uncertainties but a gap of -2.6 % was found with the one established in the 2 cm diameter beam. As a result, the DAP can be used if the sensitive surface is much larger than the beam section.

The two most common methods to measure resting metabolic rate using indirect calorimetry are steady state or time interval. Steady state is commonly defined as the first five minutes in which oxygen consumption and carbon dioxide production vary by <10%. A time interval measurement generally lasts 20-60 minutes. Using steady state criteria is often harder to achieve, but many suggest it more accurately measures resting metabolic rate. Our objective was to determine if there were differences between steady state and time interval measurements in a healthy adult population. Seventy seven subjects were measured for 45 minutes. Inclusion criteria included healthy subjects ages 18-65, excluding pregnant and lactating women. Paired t-tests analyzed differences between measures, and Bland-Altman plots evaluated bias, precision, and accuracy. Of 77 subjects, 84% achieved steady state, and 95% achieved SS by minute 30. Most differences between steady state and time intervals were statistically but not practically significant. Bland-Altman plots showed steady state measurements were generally lower indicating that steady state is more indicative of resting metabolic rate. Minutes 6-25 were most precise, accurate and fairly unbiased compared to steady state. We recommend measuring a subject for 30 minutes and using steady state criteria of <10% variation of oxygen consumption and carbon dioxide production for five minutes if a subject is able to achieve it. However, if a subject cannot achieve steady state, we recommend averaging minutes 6-25.

Acute lymphoblastic leukemia, one of the most malignant cancer forms in children is commonly treated with the thiopurine 6-mercaptopurine (6-MP) in combination with a high dose of methotrexate (MTX). 6-Mercaptopurine is in the body metabolized by the enzyme thiopurine S-methyltransferase (TPMT). Polymorphic variants of TPMT express different catalytic activities, and for this reason the dosage of 6-MP needs to be individualized. In order to better optimize the treatment it is important to understand how mutations in TPMT affect its enzymatic activity. In this thesis we have investigated how the wild type and two variants of TPMT interact with different ligands using fluorescence and isothermal titration calorimetry. Experiments with MTX, ANS and furosemide resulted in a similar binding strength for the wild type and the variant TPMT*8, while the other variant TPMT*6 showed a slightly weaker binding. A binding affinity for polyglutamated MTX to TPMTwt was also determined which resulted in an almost twice as strong binding compared to MTX. Today’s methods to determine enzymatic activity are either based on radioactivity, time consuming or expensive. As an alternative the use of a spectrophotometric assay using 5-thio-2-nitrobenzoic acid (TNB) was investigated. The method showed positive results and could hopefully be adapted to plate readers in future experiments. Using 5.5’-dithiobis-(2-nitrobenzoic acid) (DTNB, also known as Ellman’s reagent) the amount of accessible thiol groups on the protein was estimated. This revealed a similar relationship between TPMTwt and TPMT*6, while the result for TPMT*8 was inconclusive.

Purpose: Accelerometry is commonly used to objectively measure physical activity (PA), however, differential data collection methods and analysis techniques yield dissimilar outcomes. The aims of this research were to (1) understand how accelerometer output varies among accelerometers worn on the non-dominant wrist (NDW), dominant wrist (DW), and hip; (2) develop site-specific algorithms to predict activity type classification, activity intensity classification, and estimates of metabolic intensity; and (3) compare the algorithms in a free-living setting. Methods: Forty participants (16.8 – 64.2 yr) completed a sequence of sedentary and physical activities in a laboratory while wearing accelerometers on the NDW, DW, and hip. Participants also wore a portable metabolic analyzer to objectively measure oxygen consumption (VO2). One-second accelerometer output was compared across wear locations by activity type and intensity classifications (Aim 1). Accelerometer output data were transformed into variables related to the magnitude (ϒ), horizontal angle (φ), and inclination (θ) of acceleration, and used to develop algorithms for the NDW, DW, and hip. Random forest algorithms were developed to predict activity type classification (i.e., sedentary, lifestyle, and ambulatory) and activity intensity classification (i.e., sedentary, light, moderate, and vigorous), and regression models were built to predict VO2 (Aim 2). Following the laboratory visit, participants simultaneously wore an accelerometer at each of the three locations for three days of free-living data collection. The site-specific algorithms developed in Aim 2 were compared for equivalence (Aim 3). Aim 1 Results: Analysis of variance indicated that accelerometer output differed between the NDW, DW, and hip for all activities completed, except for lying supine. Differences were expected; thus, Pearson correlation coefficients were calculated between the NDW, DW, and hip, and compared across activity type and intensity classifications. For activity type, the relationships between all wear locations were different for all activity types (i.e., sedentary, lifestyle PA, and ambulatory PA). For activity intensity, the relationships between the wrists were significantly different between sedentary and light activities. Additionally, relationships between the NDW, DW, and hip differed between light and moderate, and light and vigorous PA for all wear locations. The disparate correlations indicated that accelerometer signals do not just increase in magnitude as intensity increases; rather they increase differentially by wear location and activity type. Aim 2 Results: Site-specific random forest algorithms were developed to predict activity type and intensity classification. The algorithms utilized 10-15 features of the accelerometer signal related to variability, location, and central tendency. The hip had prediction accuracies of 84.9% for activity type classification and 80.2% for activity intensity classification. The dominant wrist had activity type prediction accuracy of 83.6% and intensity prediction accuracy of 78.9%. The non-dominant wrist had prediction accuracies of 83.1% and 78.0% for activity type and intensity, respectively. The VO2 prediction algorithms had Mean Absolute Errors of 2.96 ml/kg/min for the hip, 3.34 ml/kg/min for the NDW, and 3.49 ml/kg/min for the DW. This equates to an average error of 0.93 metabolic equivalents (METs); algorithms currently used in practice yield errors of 0.89 to 2.00 METs. Aim 3 Results: The site-specific prediction algorithms were applied to free-living data. Using the random forest algorithms, activity type classification estimates differed by 2 to 82 minutes/day, and activity intensity classification estimates differed by 0 to 83 minutes/day; however, these differences were not significantly different. The VO2 prediction models provided estimates of PA within 0 to 57 minutes/day of one another. The hip provided the lowest estimates of MVPA, while the NDW provided the highest estimates, however the VO2 estimates from all wear locations were statistically equivalent to one another. Conclusion: The differential relationships among accelerometer outputs from the NDW, DW, and hip indicate that output differs based on activity type and intensity. This non-systematic error prevents scaling or comparing data collected at different wear locations and supports the need for site-specific analysis methods. Site-specific prediction algorithms provided comparable to improved performance over currently-utilized analysis methods in PA research, and the PA estimates were equivalent across wear locations. This research provides a more nuanced understanding of the impact of wear location on accelerometer output and alternative methods for analysis. Importantly, the algorithms created allow for comparisons to be made among data collected at the NDW, DW, and hip, which has not previously been possible.

This thesis contains both physics analysis and hardware studies. It consists of two primary sections: the results of a search for heavy Majorana mass neutrinos, using the event signature of same (like) sign charged electron pairs ($e^{\pm} e^{\pm}$ ) and two jets, and the results of studies to upgrade the Hadronic Forward (HF) and Hadronic Endcap (HE) subdetectors in the Compact Muon Solenoid (CMS) detector in response to the high intensity proton-proton collisions generated at the Large Hadron Collider (LHC) at European Organization for Nuclear Research (CERN, Conseil Europ\'{e}en pour la Recherche Nucl\'{e}aire). In this search for Majorana mass neutrinos, same sign dielectron ($e^{\pm} e^{\pm}$) + dijet events in the final state have been considered as a signature for neutrino particles. The analyzed data corresponds to an integrated luminosity of 19.7 fb\textsuperscript{-1} of proton-proton collisions at a center of mass energy of \begin{math}\sqrt{s} = 8\ TeV \end{math}, collected using the CMS detector during the 2012 operation at the LHC. Monte Carlo simulations accounting for the theoretical expectations of the Standard Model (SM) and the detector limitations are used to prototype the experiment and to test proposed analysis steps. No excess of events is observed in the data beyond the expected SM background. Upper limits are set on the mixing element squared, $|{V}_{eN}|^{2}$, of the heavy Majorana neutrino with standard model neutrinos, as a function of Majorana neutrino mass for masses in the range of 40-500 $GeV/c^2$. The detector upgrade search comprises three sections of this thesis. The first section describes the test results of 1785 multianode Hamamatsu R7600U-200-M4 photomultiplier tubes (PMT) in numerous parameters such as gain, dark current, and timing characteristics, which provide insights on the expected performance of the upgraded CMS-HF detector. These PMTs replaced the previous single anode R7525 PMTs because the glass windows of previous PMTs are the source of Cherenkov radiation, which causes a background noise in the experiment. The second section reports characterization results of two types of PMTs in a novel operation mode for Secondary Emission (SE) Ionization Calorimetry, which is a novel technique to measure electromagnetic shower particles in extreme radiation environments. The third section presents the test results of novel scintillating materials for CMS experiment in specific and future particle accelerators in general. These materials are Polyethylene Naphthalate (PEN), Polyethylene Terephthalate (PET), high efficiency mirror (HEM) and quartz plates with various organic and inorganic coating materials such as p-Terphenyl (pTp), Anthracene and Gallium-doped Zinc Oxide (ZnO:Ga). We have investigated them for radiation hardness, light yield, timing characteristics, and scintillation and transmission properties.