Introdução- Considerando o papel da glutamina como substrato energético para os enterácitos e como fornecedora de nitrogênio para o músculo esquelético, o estudo hipotetiza que a suplementação com glutamina pode contribuir na modulação da inflamação sistêmica e na preservação da massa muscular de idosos. Objetivos-avaliar os efeitos da suplementação com glutamina em alguns marcadores de inflamação e de composição corporal de idosos em risco de fragilidade. Métodos-estudo randomizado duplo-cego de intervenção. Foram recrutados idosos não institucionalizados que apresentaram de um a dois critérios de fragilidade biológica. Os idosos foram distribuídos em dois grupos: um recebeu glutamina(GLU) e outro maltodextrina, utilizado como placebo(PLA) durante seis meses, em duas doses diárias. No início e ao fmal do estudo os indivíduos foram avaliados pelo peso e estatura, para cálculo do índice de massa corporal(IMC), circunferências da cintura, quadril, panturrilha e braço(CC,CQ,CP e CB) e dobra cutânea tricipital(DCT); composição corporal porbioimpedância elétrica, observando os valores de resistência(R), reactância(Xc), ângulo de fase(AF), água extra e intracelular e capacitância; força de preensão palmar(FPM); concentração sérica de citocinas (IL-IO, IL-6 e TNF-α); concentração sérica de creatinina e ureia para avaliação de função renal, por meio do cálculo da depuração de creatinina(Cockcorft&Galt); ingestão alimentar pelo recordatório alimentar de 24 horas e diário alimentar; nível de atividade fisica pelo questionário de Baecke; funcionamento intestinal pela escala de Bristol. Resultados-Foram incluídos no estudo 49 idosos, divididos 25 no GLU e 24 no PLA. Embora nenhuma das variáveis tenha apontado diferença significativa na comparação relacionada ao tempo (antes e depois da suplementação) e ao tratamento (glutamina ou placebo), a evolução de algumas variáveis indicou vantagens para o GLU, a saber: maiores valores de FPM; maiores valores do IMC, ligeiro aumento da CB e ligeira diminuição da DCT, menores variações das outras medidas corporais; valores de Xc, AF e água intracelular mostraram um melhor estado celular no GLU. Conclusões-A suplementação com glutamina em idosos em risco de fragilidade mostrou variações que podem ser interpretadas como possíveis beneficios ao funcionamento intestinal e à composição corporal. Dada a grande variabilidade dos resultados, não foi possível estabelecer diferenças estatísticas que pudessem confirmar essas variações. Estudos com amostras maiores, e com medidas prévias da permeabilidade intestinal, podem esclarecer os achados. / Introduction-Having in mind the role of glutamine as an energy substrate to enterocytes, as well as a nitrogen reserve to skeletal muscle, the study hypothesized that glutamine supplementation is capable of modulating the systemic inflammation and improving muscle mass as consequence. Objectives-to evaluate the effects of glutamine supplementation on some inflammatory markers and on the body composition of elderly in risk of frailty. Methods-randomized double-blind clinicai trial (RCT). This study included community-dwelling elderly (above 65 years old), who presented one or two criteria to develop frailty syndrome. The elderly were distributed in two groups, one of them received glutamine (GLU) and the other received placebo (PLA; maltodextrin) for 6 months, in two daily doses. In beginning and cnd of the experiment, the participants were evaluated for body weight and body height, to calculate the body mass index(BMI); waist, hip, calf and arm circumferences(WC,HC,CC,AC); tricipital skin folder(TSF); body composition by bioelectrical impedance measuring resistance, reactance, capacitance, phase angle, extra and intracellular water; grip strength; serum levei of inflammatory cytokines(IL-l0, IL-6 e TNF-α); serum creatinine and urea with evaluation ofkidney function by Cockcroft & Galt equation; food intake by a 24h food record; physical activity level by Baecke questionnaire; bowel function by Bristol scale. Results-49 participants were recruited, and distributed to both groups (GLU= 24 and PLA=24). Although none of the variables showed significant statistical differences, comparing together time (before and after) and group (glutamine or placebo), but evoluation of variables to demonstrate advantages to GLU supplementation, such as: higher grip strength values; higher values of BMI, slight enhance of AC and slight reduction in TSF, lower variation in anthropometric measures; BIA results showed better cellular conditions in GLU group (from reactance, phase angle and intracellular water). Conclusions - According to our experimental conditions, the glutamine supplementation in elderly at frailty risk showed some variability which could be interpreted as benefits either to body composition and gut function. However, due to the high variability presented in the results, it was not possible to find statistical significances, to confirm those finds. Studies involving a larger sample size, and preferably with measures of intestinal permeability, could clarify our results.

Numerous studies have suggested rapid weight gain following diagnosis and initial treatment of childhood craniopharyngioma (CP) due to the damage sustained by the hypothalamus. Hypothalamic lesions formed by the treatment of the tumor and/or by invasiveness of the tumor itself are known to cause intractable weight gain, known as hypothalamic obesity. In contrast, hypothalamic obesity manifested in pediatric low-grade glioma (PLGG) patients is not as prominently addressed in literature; likely due to the expansive set of histological tumor subtypes that makes generalization challenging. Specifically, there is a lack of analysis that examines the difference in treatment, endocrinopathies, and weight gain between CP and PLGG patients. The purpose of this study was to compare hypothalamic damage in subjects diagnosed with pediatric hypothalamic low-grade glioma versus subjects diagnosed with childhood craniopharyngioma. We hypothesized that CP patients will have a more rapid post diagnosis weight gain and a greater degree of obesity compared with PLGG patients due to the more invasive nature of the tumor and the aggressive surgical treatments involved. We performed a retrospective review of the clinical records of patients who received a diagnosis of childhood craniopharyngioma or pediatric low-grade glioma at Dana-Farber Cancer Institute between 1980 and 2009. We identified 45 patients, who met criteria for evaluation, 28 were previously diagnosed with childhood craniopharyngioma and 17 were diagnosed with hypothalamic pediatric low-grade glioma. We analyzed the impact of treatment, the presence of endocrinopathies, and weight gain after diagnosis. We concluded that there was no statistically significant difference in the rate or magnitude of post diagnosis weight gain, disproving our initial hypotheses.

Low grade heat (LGH) sources, here defined as below 80ºC, are one group of abundant energy sources that are under-utilised in the production of electricity. Industrial waste heat provides a convenient source of concentrated LGH, while solar ponds and geothermal resources are examples of sustainable sources of this energy. For a number of years RMIT has had two ongoing, parallel heat engine research projects aimed at the conversion of LGH into electricity. The Thermosyphon Rankine Engine (TSR) is a heat engine that uses water under considerable vacuum. The other research stream uses a hydrocarbon based working fluid in a heat engine employing the Trilateral Flash Cycle (TFC). The TSR Mk V was designed and built as a low cost heat engine for the conversion of LGH into electricity. Its main design advantages are its cost and the employment of only one moving part. Using the data gained from the experimental rig, deviations from the expected results (those derived theoretically) were explored to gain insight for further development. The results from the TSR rig were well below those expected from the design specifications. Although the experimental apparatus was able to process the required heat energy, the efficiency of conversion fell well below the expected 3% and was approximately 0.2%. The inefficiency was explained by a number of contributing factors, the major being form drag upon the rotor that contributed around 2/3 of the losses. Although this was the major cause of the power loss, other factors such as the interference with the rotor by the condensate on its return path contributed to the overall poor performance of the TSR Mk V. The RMIT TFC project came about from exploration of the available academic literature on the subject of LGH conversion. Early work by researchers into applying Carnot's theory to finite heat sources led them to explore the merits of sensible heat transfer combined with a cycle that passes a liquid (instead of a gas) though an expander. The results showed that it was theoretically possible to extract and convert more energy from a heat source of this type using this method than using any other alternative. This previous research was targeted at heat sources above 80ºC and so exploration of the theoretical and empirical results for sources below this temperature was needed. Computer models and an experimental rig using isopentane (with a 28ºC boiling point at atmospheric pressure) were produced to assess the outcomes of employing low temperature heat sources using a TFC. The experimental results from the TFC research proved promising with the efficiency of conversion ranging from 0.8% to 2.4%. Although s uch figures seem poor in isolation, it should be noted that the 2.4% efficiency represents an achievement of 47% of the theoretical ideal conversion efficiency in a rig that uses mainly off-the-shelf components. It also confirms that the TFC shows promise when applied to heat sources less than 80ºC.

Chlorite and corrensite are very common secondary minerals in very low-grade metamorphic or hydrothermally altered mafic rocks. Corrensite, although defined as a 1:1 regularly mixed-layered chlorite/smectite or chlorite/vermiculite, has been considered as a unique mineral phase and might thus be a potential index mineral for evaluating very low metamorphic grade. Many lenticular basaltic rocks, which are intercalated with unmetamorphosed to low-grade metamorphosed Tertiary sedimentary rocks, occur sporadically in the Western foothills and the Central Range in Taiwan. The lenticular basaltic rocks in the Western foothills (diagenetic zone) and the western flank of the Central Range (anchizone to epizone) were subjected to different degrees of hydrothermal alteration and/or metamorphism. However, only few occurrences of corrensite in these basaltic rocks were reported. In the present study, the occurrences and mixed-layering features of corrensite and coexisting chloritic minerals in the basaltic rocks were characterized by utilizing optical microscopy, X-ray diffraction, scanning electron microscopy with energy dispersive spectrometry, and transmission electron microscopy (TEM). The results showed that most of these basaltic rocks contain abundant chloritic minerals occurring as replacements of mafic minerals or interstitial glass, or as vein- or vesicle-filling materials. The chloritic minerals include smectite, corrensite, chlorite, mixed-layered chlorite/smectite, or mixed-layered chlorite/corrensite. The compositions of chlorite, corrensite, and smectite are distinctive in terms of their Si/Al ratios, interlayer cations, and total cation numbers. Corrensite, chlorite, and mixed-layered chlorite/corrensite are common secondary mineral assemblages in the anchizone basaltic rocks, whereas only discrete chlorite occur in the epizone. The basaltic rocks in the diagenetic zone contain different assemblages, such as smectite only, chlorite + smectite + mixed-layered chlorite/smectite + mixed-layered chlorite/corrensite, or chlorite + corrensite + mixed-layered chlorite/corrensite. These different assemblages of chloritic minerals and other secondary mineral assemblages might reflect different stages of hydrothermal alteration. Corrensite was positively identified with TEM lattice-fringe imaging in the diagenetic rocks collected from Nangang, Poneikeng, Shanzijiao, Nanshihjiao, Hsiungkong, Shihsiouping, Fusing, and Northern Shihmen Reservoir areas, and in the studied anchizone rocks from Junghua, Kaopo and Baolai areas. The disappearance of corrensite clearly marks the boundary between the anchizone and epizone basaltic rocks. Corrensite, as a chemically and structurally unique mineral phase, is therefore a potential index mineral in very low-grade metamorphic rocks.

Background: Gliomas are neuroepithelial tumours classified by cell type and grade. In adults, low-grade gliomas are comprised mainly of astrocytomas and oligodendrogliomas grade II. The aim was to non-invasively characterise suspected low-grade gliomas through use of 11C-methionine-PET and physiological MRI in order to facilitate treatment decisions. Materials and methods: Patients with suspected low-grade glioma were prospectively and consecutively included after referral to the Neurosurgical Department, Uppsala University Hospital, between February 2010 and February 2014. All patients underwent morphological MRI, perfusion MRI, diffusion MRI and 11C-methionine PET. The institutional review board approved the study, and written informed consent was obtained prior to participation from each patient. Results: 11C-methionine PET hot spot regions corresponded spatially with regions of maximum relative cerebral blood volume in dynamic susceptibility contrast (DSC) perfusion MRI. The skewness of the transfer constantin dynamic contrast-enhanced (DCE) perfusion MRI, and the standard deviation of relative cerebral blood flow in DSC perfusion MRI could most efficiently discriminate between glioma grades II and III. In diffusion MRI, tumour fractional anisotropy differed between suspected low-grade gliomas of different neuropathological types. Quantitative diffusion tensor tractography was applicable for the evaluation of tract segment infiltration. Conclusion: PET and physiological MRI are able to characterise low-grade gliomas and are promising tools for guiding therapy and clinical decisions before neuropathological diagnosis has been obtained.

Gliomas are common primary brain tumours that occur as low-grade (LGG) and high-grade gliomas (HGG). Typically occurring in younger adults, LGG has an indolent course with a median survival of 5-10 years, but carries an inherent potential for transforming into HGG. The thesis focused on LGG in adults, with the aim of identifying prognostic biomarkers for LGG. Paper I. Epileptic seizures are common symptoms in LGG. In a retrospective study, the correlation between 11C-methionine (MET) uptake, measured by Positron Emission Tomography (PET), and seizure activity was assessed in 101 patients with LGG. Although there was no correlation between MET uptake and seizure activity, survival was longer in patients who were seizure-free before surgery. Paper II. This finding prompted the search for common genetic pathways for both tumour and seizure development and a review of genetic polymorphisms in focal epilepsy and glioma risk. Cell cycle and immune response genes affecting both glioma and seizure risk were identified, and genes involved in synaptic transmission presented potential candidates for future studies. Paper III. The transcription factor PROX1 plays a pivotal role in normal development and carcinogenesis of various organs. The prognostic value of PROX1, together with established clinical and molecular prognostic factors for survival, was retrospectively assessed in 116 patients with LGG. High PROX1 expression in the tumour was associated with shorter survival. Paper IV. DNA repair enzymes, such as ERCC6, are crucial for maintaining genomic stability in glioma response to radiotherapy. An association between the polymorphism rs4253079, mapped to ERCC6, and longer survival in patients with LGG and HGG was identified. Paper V. As LGG typically presented as non-contrast enhancing tumours on morphological MRI (magnetic resonance imaging), the value of combined MET PET with physiological MRI for preoperative diagnosis was assessed in a prospective study of 32 patients with suspected LGG. Representative tumour areas were identified through a combination of perfusion-MRI with MET PET, which can be used as a baseline investigation for follow-up over time. Conclusions: The parameters seizure-freedom before surgery, the polymorphism rs4253079 in ERCC6 and low PROX1 expression in the tumor were identified as favorable prognostic biomarkers.

PURPOSE: To determine the accuracy of prostate biopsy Gleason score (GS) compared to prostatectomy GS. To determine whether a biopsy is a satisfactory diagnostic procedure to offer active surveillance for patients with low-grade prostate cancer. METHODS: This study was conducted in Tuft Medical Center as retrospective cohort study over the period from 2007-2010. The study included 83 patients for whom biopsy and prostatectomy GS were available. MEASUREMENTS: Gleason scores of 6, 7, and 8-10 were assigned to low, moderate, and high-grades, respectively. The kappa statistic was calculated to assess the degree of agreement between biopsy and prostatectomy. The ROC curve was used to evaluate the sensitivity and specificity of prostate biopsy for different Gleason grades. Also, compared whether the use of specific criteria for active surveillance (Johns Hopkins and UCSF) may decrease the level of up-grading in patient with low-grade prostate cancer using Chi-square test. RESULTS: The distribution of low, moderate, and high-grade cancer in biopsy (52%, 32%, 16%) and prostatectomy specimen (33%, 55%, 12%) showed fair agreement with weighted kappa 0.35. The prostate biopsy accurately predicted GS in 46%, up-graded in 38%, and down-graded in 16%. The patients with low-grade cancer and potentially eligible for active surveillance showed up-grading in 50% of cases. This up-grading reduced to 40% with the use of Johns Hopkins criteria and to 41% with the use of UCSF criteria. CONCLUSIONS: The accuracy of biopsy GS in predicting prostatectomy GS is severely limited and therefore biopsy is not enough diagnostic procedure to offer active surveillance.

Globally, there are vast amounts of low-grade heat sources from industrial waste and renewables that can be converted into electricity through advanced thermodynamic power cycles and appropriate working fluids. In this thesis, experimental research was conducted to investigate the performance of a small-scale Organic Rankine Cycle (ORC) system under different operating conditions. The experimental setup consisted of typical ORC system components, such as a turboexpander with a high speed generator, a scroll expander, a finned-tube condenser, an ORC pump, a plate evaporator and a shell and tube evaporator. R245fa was selected as the working fluid, on account of its appropriate thermophysical properties for the ORC system and its low ozone depletion potential (ODP). The test rig was fully instrumented and extensive experiments carried out to examine the influences of several important parameters, including heat source temperature, ORC pump speed, heat sink flow velocity, different evaporators and with or without a recuperator on overall R245fa ORC performances. In addition, in terms of the working fluid’s environmental impact, temperature match of the cycle heat processes and system compactness, CO2 transcritical power cycles (T-CO2) were deemed more applicable for converting low-grade heat to power. However, the system thermal efficiency of T-CO2 requires further improvement. Subsequently, a test rig of a small-scale power generation system with T-CO2 power cycles was developed with essential components connected; these included a plate CO2 supercritical heater, a CO2 transcritical turbine, a plate recuperator, an air-cooled finned-tube CO2 condenser and a CO2 liquid pump. Various preliminary test results from the system measurements are demonstrated in this thesis. At the end, a theoretical study was conducted to investigate and compare the performance of T-CO2 and R245fa ORCs using low-grade thermal energy to produce useful shaft or electrical power. The thermodynamic models of both cycles were developed and applied to calculate and compare the cycle thermal and exergy efficiencies at different operating conditions and control strategies. In this thesis, the main results showed that the thermal efficiency of the tested ORC system could be improved with an increased heat source temperature in the system with or without recuperator. When the heat source temperature increased from 145 oC to 155 oC for the system without recuperator, the percentage increase rates of turbine power output and system thermal efficiency were 13.6% and 14% respectively while when the temperature increased from 154 oC to 166 oC for the system with recuperator, the percentage increase rates were 31.2% and 61.97% respectively. In addition, the ORC with recuperator required a relative higher heat source temperature, which is comparable to a system without recuperator. On the other hand, at constant heat source temperatures, the working fluid pump speed could be optimised to maximise system thermal efficiency for ORC both with and without recuperator. The pressure ratio is a key factor impacting the efficiencies and power generation of the turbine and scroll expander. Maximum electrical power outputs of 1556.24W and 750W of the scroll expander and turbine were observed at pressure ratio points of 3.3 and 2.57 respectively. For the T-CO2 system, the main results showing that the CO2 mass flow rate could be directly controlled by varying the CO2 liquid pump speeds. The CO2 pressures at the turbine inlet and outlet and turbine power generation all increased with higher CO2 mass flow rates. When CO2 mass flow rate increased from 0.2 kg/s to 0.26kg/s, the maximum percentage increase rates of measured turbine power generation was 116.9%. However, the heat source flow rate was found to have almost negligible impact on system performance. When the thermal oil flow rate increased from 0.364kg/s to 0.463kg/s, the maximum percentage increase rate of measured turbine power generation was only 14.8%. For the thermodynamic analysis, with the same operating conditions and heat transfer assumptions, the thermal and exergy efficiencies of R245fa ORCs are both slightly higher than those of T-CO2. However, the efficiencies of both cycles can be enhanced by installing a recuperator at under specific operating conditions. The experiment and simulation results can thus inform further design and operation optimisations of both the systems and their components.

Les gliomes diffus de bas grades sont des tumeurs qui affectent des régions fonctionnelles du cerveau chez des jeunes patients. Malgré leur faible taux de prolifération ces tumeurs peuvent dégénérer en des tumeurs plus agressives après leurs exérèses. Le gène IDH1 est très fréquemment muté dans les DLGG. Cette mutation confère à l’enzyme isocitratedeshydrogénase (IDH1) la propriété de produire du 2-OH-glutarate (2-HG) au lieu de l’α-cétoglutarate (α-KG). L’oncométabolite 2HG rentre alors en compétition avec l’α-KG pour les enzymes de déméthylation conduisant à une hyperméthylation de l’ADN et de l’histone H3 concourant à un blocage de la différenciation cellulaire. Mon projet de thèse consiste à la caractérisation des cellules tumorales et la compréhension des voies de signalisation impliquées dans la progression tumorale ainsi que l’identité du microenvironnement tumoral. Les récepteurs tyrosine kinase, PDGFRα et EGFR, sont abondamment exprimés par les cellules tumorales mais ne sont pas activés. En revanche, une forte phosphorylation de la protéine Erk p42/44 a été détectée dans les tumeurs. Cette phosphorylation a une double origine : les cellules tumorales et leur environnement. L’utilisation d’une série de marqueurs m’a permis de mieux définir l’état de différenciation des cellules tumorales et de mettre en évidence une préférence pour l’expression de Sox8 dans les oligodendrogliomes tandis que Sox9 est prédominant dans les astrocytomes. Dans une seconde partie, j’ai mis au point des méthodes pour la culture des gliomes diffus de bas grade et isolé cinq lignées de gliomes portant la mutation récurente IDH1 R132H. Récemment, la société Agios a identifié des inhibiteurs très spécifiques (notamment l’AGI-5198) de l’enzyme mutée IDH1 qui, utilisés dans un modèle de gliome murin, provoquent une déméthylation des histones H3K9me3 associées à une augmentation de l’expression de gènes de différenciation ainsi qu’à une réduction de la masse tumorale. A contrario, j’ai montré que l’AGI-5198 augmente la croissance cellulaire sur les lignée de patients, modifie la migration cellulaire ainsi que différentes voies de signalisation.Ces travaux apportent un nouvel éclairage sur le phénotype des cellules tumorales, leur diversité et les mécanismes moléculaires régissant leur prolifération. / Low grade gliomas are low proliferating tumors affecting functional regions of young patients. In most cases, they tend to transform into a more malignant state following surgery. These tumors carry a key mutation in isocitrate dehydrogenase (70-80% of DLGG). Gliomas with IDH1 mutation have improved prognosis compared togliomaswith wild type IDH1. IDH1 protein acquires the ability to convert α-Ketoglutarate (α-KG) to 2-OH-glutarate (2-HG). The new onco-metabolite can interfere with the normal function of α-KG, leading to a general hypermethylation of the genome, thus inducing a blockage of the cellular differentiation. Very good reviews on the molecular mechanisms underlying high grade glioma invasion already exist but little is known about the cellular and molecular mechanisms in diffuse low grade gliomas. To that end, I characterized the profile of IDH1 mutated cells in the different types of DLGG. I have demonstrated that the tyrosine kinase, PDGFRα and EGFR receptors are abundantly expressed by tumor cells eventhough they are not activated. In contrast, a strong phosphorylation of Erk p42 / 44 proteins was detected in these tumors. This phosphorylation has a dual origin: tumor cells and their environment. The use of a series of markers allowed me to better define the state of differentiation of cancerous cells and to demonstrate a preferential expression of Sox8 in oligodendrogliomas while Sox9 is predominant in astrocytomas. In a second time, I have developed a method for the culture of low-grade diffuse gliomas and isolated five cell lines carrying the recurrent mutation IDH1 R132H. Recently Agios has identified very specific inhibitors (particularly AGI-5198) of the mutated IDH1 enzyme which, used in a murine glioma model, contributed to the demethylation of H3K9me3 histones with an increased expression of differentiation related genes as well as a reduction of the tumor mass. On the contrary, I have shown that AGI-5198 increases cell growth of patient cell lines, modifies the cellular migration and various signaling pathways.These studies shed new light on the phenotype of tumor cells, their diversity and The molecular mechanisms governing their proliferation.

abstract: About 20-50% of industrial processes energy is lost as waste heat in their operations. The thermal hydraulic engine relies on the thermodynamic properties of supercritical carbon dioxide (CO2) to efficiently perform work. Carbon dioxide possesses great properties that makes it a safe working fluid for the engine’s applications. This research aims to preliminarily investigate the actual efficiency which can be obtained through experimental data and compare that to the Carnot or theoretical maximum efficiency. The actual efficiency is investigated through three approaches. However, only the efficiency results from the second method are validated since the other approaches are based on a complete actual cycle which was not achieved for the engine. The efficiency of the thermal hydraulic engine is found to be in the range of 0.5% to 2.2% based on the second method which relies on the boundary work by the piston. The heating and cooling phases of the engine’s operation are viewed on both the T-s (temperature-entropy) and p-v (pressure-volume) diagrams. The Carnot efficiency is also found to be 13.7% from a temperature difference of 46.20C based on the measured experimental data. It is recommended that the thermodynamic cycle and efficiency investigation be repeated using an improved heat exchanger design to reduce energy losses and gains during both the heating and cooling phases. The temperature of CO2 can be measured through direct contact with the thermocouple and pressure measurements can be improved using a digital pressure transducer for the thermodynamic cycle investigation. / Dissertation/Thesis / Masters Thesis Mechanical Engineering 2020