A potencialidade do eletrodo de cobre em meio alcalino foi demonstrada para o determinação de etanol a +0,6 V vs Ag/AgCl. A participação de espécies solúveis de Cu(III) no processo eletrocatalítico envolvendo a oxidação do etanol foi demonstrada por experimentos utilizando eletrodo disco-anel. A influência do potencial de pré-tratamento no sinal anódico foi investigada e correlacionada com a morfologia dos filmes formados na superfície do eletrodo por EDS (Energy Dispersive X-Ray Spectroscopy), indicando que as espécies de Cu(III) são originadas a partir da oxidação da camada de CuO. As medidas de etanol foram realizadas por amperometria em 0,6 V (vs Ag/AgCl). A repetibilidade das medidas utilizando padrão aquoso de etanol 0,05 % (v/v) foi de 3 % (v/v) e os limites de detecção e quantificação foram de 0,005 % (v/v) e 0,01 % (v/v), respectivamente. Nas condições experimentais otimizadas, o sensor amperométrico foi utilizado para o monitoramento da concentração de etanol no ar exalado (BrAC), que foi convenientemente coletado em um balão de borracha (V = 3 L) e introduzido em uma solução de NaOH 1 mol L-1 (V = 10 mL). O sensor apresentou uma faixa linear para concentrações de etanol em ar exalado na faixa de 0,26 – 130 mg L-1, operando de acordo com os parâmetros analíticos especificados na Legislação Brasileira para a quantificação de etanol no ar exalado em condutores de veículos automotores. A constante de eliminação de etanol do corpo humano também foi investigada e os resultados concordaram com os valores da literatura. Empregando-se eletrodos de Cu e Au foram também desenvolvidas outras metodologias para a quantificação de dipirona, glicose e ácido ascórbico e sistemas em fluxo. Estudos sobre o desenvolvimento e propriedades de um sistema gerador-coletor foram realizados e o dispositivo foi utilizado em titulações de substâncias redutoras com iodo gerado eletroquimicamente. / A copper disc working electrode in alkaline solutions was demonstrated to act as a suitable amperometric sensor for ethanol determination at +0.6 V vs Ag/AgCl. The participation of free-soluble Cu(III) species in the electrocatalytic process involving the anodic oxidation of ethanol has been demonstrated by rotating ring-disc electrode voltammetry. The influence of the pretreatment potential on the anodic signal was investigated and a correlation with the morphology of the electrode surface characterized by Energy Dispersive X-Ray Spectroscopy (EDS) indicated that the Cu(III) species is originated from the oxidation of a CuO layer. Ethanol measurements were performed in the amperometric mode at 0.6 V (vs Ag/AgCl). The repeatability of the measurements for a 0.05 % aqueous ethanol solution was estimated as 3 %, and the detection and quantification limits were determined as 0.005 % and 0.01 %, respectively. At the optimum experimental conditions, the amperometric sensor was used to monitor the concentration of ethanol in breath (BrAC), which was conveniently collected in a rubber air balloon (volume = 3 L) and introduced in a 1 mol L-1 NaOH working solution (volume = 10 mL). The sensor can measure a person\'s breath ethanol over the concentration range 0.26 - 130 mg L-1 by operating it according to an established protocol, of which the analytical parameters are specified by the Brazilian Legislation for BrAC measurements in drivers. The rate of ethanol degradation in the body was followed, and the results agree with predictions in the literature. Methodologies for the determination of dipyrone, glucose and ascorbic acid were also developed by using Cu and Au electrodes. Features of a dual-band electrochemical cell were investigated towards the development of a generator-collector system, which was employed in titrations with electrogenerated iodine.

Avaliamos as mudanças no padrão respiratório, movimento toracoabdominal e ventilação em portadores de DPOC e indivíduos sadios. Estudou-se 45 indivíduos entre 45 e 75 anos conforme o VEF1. Utilizou-se sistemas de pletismografia respiratória por indutância, análise metabólica de gases em posição semi-sentada ao repouso e radiografia de tórax para a mobilidade diafragmática. Os grupos DPOC apresentaram redução do TI, TTOT, aumento do VC/TI, f, VE, das relações VEM/VC, VE/VO2, VE/VCO2 e diminuição da SpO2. Redução da mobilidade do diafragma e aumento da VEM/VC associaram-se à ineficiência da ventilação e a alterações no modelo ventilatório utilizado, sem alterações no movimento toracoabdominal. / We assessed changes in breathing patterns, thoracoabdominal movement and ventilation in COPD sufferers and healthy individuals. Forty-five individuals between 45 and 75 were grouped by FEV1. Inductive plethysmographic equipment, respiratory metabolism measuring (with subject at rest in semi-recumbent position), and radiographic measurement of diaphragm mobility were used. The COPD groups presented reduction in TI and TTOT and increased VT/TI, f, VE, and VD/VT, VE/VO2, VE/VCO2 and decreased SpO2. Reduction in diaphragm mobility and increase of VEM/VC were associated with ventilatory inefficiency and alterations in the ventilatory model used. No alterations in thoracoabdominal movement

The growth of sensors and sensing technologies have made significant impact in our day-to-day life. The five principle sensory organs of our body should perform effectively, so that we can lead a good healthy life. Apart from these natural sensors, there are man-made sensors that helps us to cope with diseases, organ failure etc. and enable us to lead a normal life. In recent years, with the prevalence of new kind of diseases, the need for new type of biomedical sensors is becoming very important. As a result, sensors used for biomedical applications have become an emerging technology and rapidly growing field of research. The aim of the present thesis work is to use the piezoelectric property of Polyvinylidene Fluoride (PVDF) film for the development of biomedical sensor and studying its application for human respiration/breathing related abnormalities. PVDF nasal sensor was designed in cantilever configuration and detailed theoretical analysis of the same was performed. Based on theoretical and experimental results, the PVDF nasal sensor dimensions were optimized. Suitable signal conditioning circuitry was designed and a measurement system for biomedical application was developed. The developed PVDF nasal sensor was calibrated using MEMS low-pressure sensor. The PVDF nasal sensor system has been applied in different biomedical applications namely, (i) to monitor human respiration pattern, (ii) to identify different Respiration Rates (RR), (iii) to evaluate Deviated Nasal Septum (DNS) in comparison with other objective method and, (vi) to clinically investigate nasal obstruction in comparison with subjective method. The thesis is divided into seven chapters. Chapter 1 This chapter gives a general introduction about biomedical sensors, piezoelectric sensing principle and PVDF polymer films along with the relevant literature survey. The brief introduction as well as literature survey of techniques used to monitor human respiration and to measure nasal obstruction is also included in this chapter. Chapter 2 This chapter gives details about the design of the PVDF nasal sensor in the cantilever configuration for sensing nasal airflow along with the relevant theoretical equations. Also, the details on the optimization of the PVDF nasal sensor dimensions based on the theoretical and experimental analysis are presented. Chapter 3 This chapter reports the designing of the necessary signal conditioning hardware along with the data acquisition unit for the PVDF nasal sensor. The signal conditioning hardware unit made consists of charge amplifier, low-pass filter and an amplifier. Besides, a complete measurement system for biomedical application was developed using PVDF nasal sensor and its merits and demerits were discussed. Chapter 4 In this chapter, an experimental set-up for measuring human respiration/breathing pressure using water U-tube manometer has been described. Also, the calibration procedure followed for the developed PVDF nasal sensor using a Micro Electro Mechanical Systems(MEMS) low pressure sensor is reported. Apart from these, the details on the measurement of deflection of the PVDF cantilever sensing element using laser displacement setup are provided. In addition, the PVDF nasal sensor was also calibrated for various air flow rates. At the end, a study has been reported on optimizing the position the PVDF nasal sensor with respect to human nose. Chapter 5 This chapter is divided into two sections, Section 5.1: This section describes the applicability of the PVDF nasal sensor using its piezoelectric property to monitor the human respiration pattern of each nostril simultaneously. The results of the PVDF nasal sensor have also been evaluated by comparing with Respiratory Inductive Plethysmograph(RIP) technique in normal subjects. Section 5.2: In this section, PVDF nasal sensor, RIP and Nasal Prongs (NP) techniques were used to measure the RR of healthy adults. The aim here was to evaluate the presently developed PVDF nasal sensor for identifying different RR compared to „Gold standard‟ RIP and NP methods. Chapter 6 This chapter is divided into two sections. Section 6.1: This section reports about the utilization of the developed PVDF nasal sensor for clinical application on the patient population. For this purpose, the performance of the PVDF nasal sensor measurements has been compared with the Peak Nasal Inspiratory Flow(PNIF) objective technique and visual analog scale (VAS). Section 6.2: This section describes about the use of PVDF nasal sensor system to measure nasal obstruction caused due to DNS objectively. Further, the results of the PVDF nasal sensor were compared with subjective techniques namely, VAS and clinician scale in patients and control group. Chapter 7 This chapter is composed of two sections. Section 7.1: This section summarizes the salient features of the work presented in this thesis. Section 7.2: This section reports a scope for carrying out further work.

.La consommation journalière de fructose est en augmentation croissante, jusqu'à plus de 50g par jour aux Etats-Unis et en Europe de l'Ouest. Le fructose est de plus en plus incorporé dans les boissons, les produits laitiers et les conserves, les produits cuisinés ou transformés. Le fructose peut déclencher ou aggraver les symptômes digestifs chez des volontaires sains, mais aussi dans le syndrome de l'intestin irritable. Le rôle de l'hypersensibilité viscérale dans le déclenchement des symptômes, lié à la prise de fructose a été suspecté mais n'a jamais été évalué. La prévalence de la malabsorption du fructose était mal documentée chez les patients souffrant d'un syndrome de l'intestin irritable, principalement en raison de l'hétérogénéité des méthodes diagnostiques. Le premier objectif de ce travail a été de définir, dans une population de patients souffrant d'un syndrome de l'intestin irritable, la prévalence de la malabsorption du fructose. Notre test de malabsorption du fructose a été défini par une dose de charge de 25g. Chez nos patients souffrant d'un syndrome de l'intestin irritable, 22% présentaient une malabsorption du fructose. Les patients jeunes et de sexe masculin étaient plus à risque de malabsorption du fructose. Nous avons également étudié l'association de la malabsorption du fructose avec d'autres anomalies physiopathologiques connues dans le syndrome de l'intestin irritable. Nous n'avons pas retrouvé d'association entre la présence d'une inflammation digestive et la présence ou non d'une malabsorption du fructose. En revanche, une association a été retrouvée entre malabsorption du fructose et hypersensibilité viscérale. L'efficacité du régime appauvri en fructose dans le syndrome de l'intestin irritable est connue. L'existence ou non d'une malabsorption du fructose associée pourrait être un facteur prédictif d'efficacité d'un tel régime. Le deuxième objectif de ce travail a été de déterminer si le test de dépistage de la malabsorption au fructose permettait de prédire l'efficacité du régime appauvri en fructose sur les symptômes digestifs des patients souffrant d'un syndrome de l'intestin irritable. Les résultats de notre étude ont confirmé l'efficacité du régime appauvri en fructose dans le syndrome de l'intestin irritable. En revanche, la présence ou non d'un test respiratoire au fructose positif n'impactait pas l'efficacité du régime. Le dernier objectif de ce travail était de modéliser la malabsorption du fructose sur des modèles murins, pour permettre d'identifier les mécanismes physiopathologiques sous-jacents. La modélisation sur 3 modèles murins de malabsorption du fructose (par régime riche en fructose, par délétion des gènes codant les transporteurs du fructose GLUT5 et GUT2) permettait d'induire une hypersensibilité viscérale associée à une augmentation de la perméabilité intestinale, deux anomalies déjà rapportées dans le syndrome de l'intestin irritable. L'étude des mécanismes physiopathologiques sous-jacents a permis d'écarter l'implication d'une inflammation de bas grade qui n'était pas retrouvée chez nos souris. L'augmentation d'activité élastase dans les selles de souris avec malabsorption du fructose était associée à l'hypersensibilité viscérale. Or il a déjà été démontré que l'activité protéasique pouvait être responsable d'une hypersensibilité viscérale et d'une augmentation de la perméabilité intestinale. Les récepteurs associés à la protéase-2 sont connus pour être associés à l'hypersensibilité viscérale et l'augmentation de la perméabilité intestinale. Les résultats obtenus dans le cadre de ce travail soulignent le rôle de la malabsorption du fructose, qui entraine la survenue d'une hypersensibilité viscérale et d'une augmentation de la perméabilité intestinale, dans le syndrome de l'intestin irritable. Un régime appauvri en fructose n'améliore pas de manière ciblée les symptômes des patients souffrant d'un syndrome de l'intestin irritable avec malabsorption du fructose. / Fructose intake has increased by up to 50 g per day in the USA and Western Europe. Fructose is increasingly incorporated in beverages, dairy products and canned, baked or processed foods worldwide. Fructose has been shown to trigger or worsen digestive symptoms not only in healthy volunteers, but also in patients with irritable bowel syndrome. The involvement of visceral hypersensitivity has been suspected but has never been assessed. The prevalence of fructose malabsorption in patients with irritable bowel syndrome in Western Europe remains poorly documented, due to the heterogeneity of available tests. Therefore, the first objective of this present work was to assess the prevalence of fructose malabsorption in patients with irritable bowel syndrome. We assessed fructose malabsorption with a fructose breath test, after a 25 g load. We systematically ruled out small intestinal bacterial overgrowth which could promote false positive. In our irritable bowel syndrome patients, 22% had fructose malabsorption. Young, male patients were more likely to have fructose malabsorption. We also assessed the association between fructose malabsorption and other abnormalities. We did not observe any association between low-grade inflammation (with faecal calprotectin dosage) or fructose malabsorption. In contrast, an association between fructose malabsorption and visceral hypersensitivity was evidenced. Low fructose diet is known to improve symptoms in patients with irritable bowel syndrome. The presence of fructose malabsorption could be predictive of the efficacy of a low fructose diet. The second objective of this work was to determine if an abnormal fructose breath test was a predictor of symptomatic response to low fructose diet in irritable bowel syndrome. Our study has confirmed the efficacy of low fructose diet on irritable bowel syndrome. However, the results of the fructose breath test had no impact on its efficacy. One explanation for this result could be the presence of other abnormalities (including visceral hypersensitivity) that were not addressed only with a diet. The last objective of this work was to model fructose malabsorption in mice, in order to identify the underlying mechanisms. We used three models of fructose malabsorption (high fructose diet, invalidation of GLUT5 and GLUT2 coding gene). In these models, fructose malabsorption induced visceral hypersensitivity and increased intestinal permeability, the two abnormalities being reported in irritable bowel syndrome. In our models, there was no low-grade inflammation. Increased elastase activity in mice faeces was associated with visceral hypersensitivity. Protease-activated receptor-2 is known to be associated with visceral hypersensitivity and increases intestinal permeability. Further works are warranted to determine the involvement of protease-activated receptor-2 in fructose malabsorption-associated visceral hypersensitivity. The results of this work underlined the role of fructose malabsorption in irritable bowel syndrome, in the onset of visceral hypersensitivity and increased intestinal permeability. A low fructose diet is not helpful to improve symptoms of irritable bowel syndrome with fructose malabsorption.

Poröse Polymermembranen spielen in der Industrie und Forschung als Filtrationsmedien eine bedeutende Rolle. Eine besondere Form dieser Membranen sind die sogenannten Mikrosiebe, die sich im Vergleich zu herkömmlichen Filtermedien durch eine Membrandicke kleiner als der Durchmesser der Poren, eine enge Porengrößenverteilung und eine hohe Porendichte auszeichnen. Dies führt zu einer hohen Selektivität und Permeabilität dieser Mikrosiebe. Aufgrund der geringen Membrandicke sind sie jedoch, beispielsweise beim Einsatz als Filtermedien, sehr empfindlich gegenüber mechanischer Belastung und benötigen üblicherweise eine zusätzliche (externe) Stützstruktur. Die vorliegende Arbeit beschäftigt sich mit der Herstellung mikrosiebartiger Polymermembranen, bei denen die Darstellung der späteren Trennschicht und Stützstruktur in einem Prozess erfolgt – den hierarchisch strukturierten porösen Membranen. Es werden zwei neue Verfahren zur Darstellung dieser Membranen vorgestellt. Im ersten Verfahren wird das Prinzip der partikel-assistierten Benetzung mit den sogenannten Kondensationsmustern (Breath Figures Patterns), im zweiten Verfahren mit der Tintenstrahltechnik kombiniert. In beiden Fällen enthalten die resultierenden Polymermembranen die gewünschte hierarchische Porenstruktur, d. h. sie weisen eine Trennschicht mit submikrometergroßen Poren auf der einen Seite und eine Stützstruktur mit größeren, mikrometergroßen Poren auf der anderen Seite auf. Um die Membranen, welche durch Kombination der partikel-assistierten Benetzung mit den Kon-densationsmustern hergestellt werden, für einen möglichen Einsatz als Filtrationsmedium zu charakterisieren, werden Untersuchungen bezüglich des Permeatflusses und der Permeabilität sowie zum Rückhaltevermögen durchgeführt.:Inhaltsverzeichnis iii Verzeichnis der verwendeten Abkürzungen und Symbole vi Abkürzungen vi Symbole ix 1 Einleitung und Motivation der Arbeit 1 2 Verfahren zur Herstellung hierarchisch strukturierter Membranen durch Kombination von Kondensationsmustern mit dem Prinzip der partikel-assistierten Benetzung 10 2.1 Einleitung 10 2.2 Ergebnisse 15 2.3 Zusammenfassung 24 2.4 Experimenteller Teil 25 2.4.1 Synthese der Siliziumdioxid-Partikel 25 2.4.2 Membranherstellung 26 2.4.2.1 Herstellung der Partikel-Polymer-Dispersionen 26 2.4.2.2 Herstellung der Membranen 28 2.4.3 Rasterelektronenmikroskopische Untersuchung 29 2.4.4 Verwendete Chemikalien 30 2.4.4.1 Herstellung der Siliziumdioxid-Partikel nach Stöber 30 2.4.4.2 Herstellung der Membranen 30 3 Untersuchung der Filtrationseigenschaften der hierarchisch strukturierten porösen Membranen 31 3.1 Einleitung 31 3.1.1 Filtration 31 3.1.2 Ultrafiltration und Mikrofiltration - Prozessführung 36 3.1.2.1 Dead-End-Filtration 37 3.1.2.2 Querstrom-Filtration 40 3.1.3 Membranfouling 41 3.1.4 Mikrofiltration mit Mikrosieben 42 3.2 Ergebnisse 45 3.2.1 Bestimmung der Porosität 46 3.2.2 Bestimmung der Leistungsfähigkeit der hierarchisch strukturierten Membranen 49 3.2.3 Bestimmung des Rückhaltevermögens der hierarchisch strukturierten Membranen 56 3.2.3.1 Filtration von Hefezellen 56 3.2.3.2 Filtration von Rhodamin B markierten Melamin-Partikeln 58 3.3 Zusammenfassung 60 3.4 Experimenteller Teil 62 3.4.1 Herstellung poröser Membranen für Filtrationsversuche 62 3.4.2 Permeatfluss- und Permeabilitätsmessungen 62 3.4.3 Filtrationsmessungen 63 3.4.3.1 Filtration von Hefezellen 63 3.4.3.2 Filtration von Rhodamin B markierten Melamin-Partikeln 64 3.4.4 Rasterelektronenmikroskopische Untersuchung 64 3.4.5 Verwendete Chemikalien 65 3.4.5.1 Herstellung der Membranen 65 3.4.5.2 Permeatfluss- und Permeabilitätsmessungen 65 3.4.5.3 Filtrationsmessungen 66 3.5 Anhang 67 3.5.1 Anhang 3.1 - Ergebnisse der Porositätsbestimmung 67 3.5.2 Anhang 3.2 - Ergebnisse der Bestimmung der Permeatflüsse und Permeabilitäten 78 3.5.3 Anhang 3.3 - Ergebnisse der Filtrationsmessungen 83 4 Herstellung poröser Membranen mittels Inkjet-Technologie 86 4.1 Einleitung 87 4.1.1 Inkjet-Technologie (Tintenstrahltechnik) 87 4.1.2 Ober- und Grenzflächenthermodynamik 91 4.1.3 Herstellung poröser Membranen mit Hilfe der Inkjet-Technologie 96 4.2 Ergebnisse 97 4.2.1 Druckprozess 98 4.2.2 Membranherstellungsprozess 104 4.2.2.1 Membranherstellung mittels Filmziehrahmen 105 4.2.2.2 Membranherstellung mittels Ringmethode 107 4.2.2.3 Vergleich zwischen theoretischem und experimentell ermitteltem Porendurchmesser 110 4.2.2.4 Porosität 116 4.3 Zusammenfassung 118 4.4 Experimenteller Teil 119 4.4.1 Herstellen der Substrate 119 4.4.2 Druckprozess 119 4.4.2.1 Herstellung der Tinte und Befüllen der Patrone 120 4.4.2.2 Einstellung des Druckers 120 4.4.3 Membranherstellung 121 4.4.3.1 Herstellung der Polymerlösungen 121 4.4.3.2 Herstellung und Aufarbeitung der Membranen 122 4.4.4 Rasterelektronenmikroskopische Untersuchung 123 4.4.5 Verwendete Chemikalien 124 4.4.5.1 Herstellung der Substrate 124 4.4.5.2 Druckprozess 124 4.4.5.3 Membranherstellung 124 4.5 Anhang 125 5 Verfahren zur Herstellung hierarchisch strukturierter Membranen durch Kombination der Inkjet-Technologie mit dem Prinzip der partikel-assistierten Benetzung 127 5.1 Einleitung 128 5.1.1 Dünne Polymerfilme 128 5.1.2 Dynamik des Verdunstungsprozesses 129 5.2 Ergebnisse 132 5.2.1 Einfluss der Partikel auf die Membranherstellung 134 5.2.2 Einfluss der Oberflächenfunktionalisierung der Partikel und des Partikel : Polymer-Verhältnisses 137 5.2.3 Einfluss des Lösungsmittels 144 5.2.3.1 Membranherstellung mit einem Lösungsmittelgemisch aus Chloroform und 1-Dekalin 146 5.2.3.2 Membranherstellung mit einem Lösungsmittelgemisch aus Chloroform und 3-Pentanon 148 5.2.3.3 Porosität 153 5.3 Zusammenfassung 155 5.4 Experimenteller Teil 158 5.4.1 Herstellung der Substrate 158 5.4.2 Druckprozess 158 5.4.2.1 Herstellung der Tinte und Befüllen der Patrone 159 5.4.2.2 Einstellung des Druckers 159 5.4.3 Membranherstellung 160 5.4.3.1 Herstellung der Siliziumdioxid-Partikel 160 5.4.3.2 Herstellung der Partikel-Polymer-Dispersion 162 5.4.3.3 Herstellung und Aufarbeitung der Membranen 164 5.4.4 Rasterelektronenmikroskopische Untersuchung 164 5.4.5 Verwendete Chemikalien 166 5.4.5.1 Synthese der Siliziumdioxid-Partikel 166 5.4.5.2 Herstellung der Substrate 167 5.4.5.3 Druckprozess 167 5.4.5.4 Membranherstellung 167 6 Zusammenfassung 168 7 Literatur 172 Abbildungsverzeichnis 180 Tabellenverzeichnis 184 Selbständigkeitserklärung 185 Circum Vitae 186 8 Literatur 191

Detection of early pathophysiological changes of breathing in children with chronic respiratory disease MD. Vaclav Koucky - Ph.D. thesis Abstract Introduction: Currently, there are different methods for infant pulmonary function testing (iPFT) and morphological assessment of microscopic changes in endobronchial biopsy samples (EBB). In research setting, they allow detection of early pathophysiological changes of breathing in small children with chronic respiratory disease, respectively in risk of its development. Their clinical significance, however, is not fully acknowledged. The aim of this thesis is to evaluate the safety, feasibility and clinical significance of iPFT and EBB in infants younger than 2 years of age. In addition, the relationship between functional and morphological changes of respiratory tract and the function of peripheral chemoreceptors was studied in selected patients' subgroups. Methods: Fifty-five infants with cystic fibrosis (CF), 35 physician-confirmed recurrent wheezers (AB), 9 infants with congenital diaphragmatic hernia, 7 with interstitial lung disease (chILD) and 3 with primary ciliary dyskinesia (PCD) were enrolled. All infants underwent iPFT and relevant clinical history data were recorded. Based on patients' age, CF group was divided into CFmalí (< 6 months) and CFvelcí (>...

Metabolomics is the methodical scientific study of biochemical processes associated with the metabolome—which comprises the entire collection of metabolites in any biological entity. Metabolome changes occur as a result of modifications in the genome and proteome, and are, therefore, directly related to cellular phenotype. Thus, metabolomic analysis is capable of providing a snapshot of cellular physiology. Untargeted metabolomics is an impartial, all-inclusive approach for detecting as many metabolites as possible without a priori knowledge of their identity. Hence, it is a valuable exploratory tool capable of providing extensive chemical information for discovery and hypothesis-generation regarding biochemical processes. A history of metabolomics and advances in the field corresponding to improved analytical technologies are described in Chapter 1 of this dissertation. Additionally, Chapter 1 introduces the analytical workflows involved in untargeted metabolomics research to provide a foundation for Chapters 2 – 5. Part I of this dissertation which encompasses Chapters 2 – 3 describes the utilization of mass spectrometry (MS)-based untargeted metabolomic analysis to acquire new insight into cancer detection. There is a knowledge deficit regarding the biochemical processes of the origin and proliferative molecular mechanisms of many types of cancer which has also led to a shortage of sensitive and specific biomarkers. Chapter 2 describes the development of an in vitro diagnostic multivariate index assay (IVDMIA) for prostate cancer (PCa) prediction based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) metabolic profiling of blood serum samples from 64 PCa patients and 50 healthy individuals. A panel of 40 metabolic spectral features was found to be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy. The performance of the IVDMIA was higher than the prevalent prostate-specific antigen blood test, thus, highlighting that a combination of multiple discriminant features yields higher predictive power for PCa detection than the univariate analysis of a single marker. Chapter 3 describes two approaches that were taken to investigate metabolic patterns for early detection of ovarian cancer (OC). First, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic high-grade serous carcinoma (HGSC) observed in women were studied. Using UPLC-MS, serum samples from 14 early-stage tumor DKO mice and 11 controls were analyzed. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for early-stage HGSC detection. In the second approach, serum metabolic phenotypes of an early-stage OC pilot patient cohort were characterized. Serum samples were collected from 24 early-stage OC patients and 40 healthy women, and subsequently analyzed using UPLC-MS. Multivariate statistical analysis employing support vector machine learning methods and recursive feature elimination selected a panel of metabolites that differentiated between age-matched samples with 100% cross-validated accuracy, sensitivity, and specificity. This small pilot study demonstrated that metabolic phenotypes may be useful for detecting early-stage OC and, thus, supports conducting larger, more comprehensive studies. Many challenges exist in the field of untargeted metabolomics. Part II of this dissertation which encompasses Chapters 4 – 5 focuses on two specific challenges. While metabolomic data may be used to generate hypothesis concerning biological processes, determining causal relationships within metabolic networks with only metabolomic data is impractical. Proteins play major roles in these networks; therefore, pairing metabolomic information with that acquired from proteomics gives a more comprehensive snapshot of perturbations to metabolic pathways. Chapter 4 describes the integration of MS- and NMR-based metabolomics with proteomics analyses to investigate the role of chemically mediated ecological interactions between Karenia brevis and two diatom competitors, Asterionellopsis glacialis and Thalassiosira pseudonana. This integrated systems biology approach showed that K. brevis allelopathy distinctively perturbed the metabolisms of these two competitors. A. glacialis had a more robust metabolic response to K. brevis allelopathy which may be a result of its repeated exposure to K. brevis blooms in the Gulf of Mexico. However, K. brevis allelopathy disrupted energy metabolism and obstructed cellular protection mechanisms including altering cell membrane components, inhibiting osmoregulation, and increasing oxidative stress in T. pseudonana. This work represents the first instance of metabolites and proteins measured simultaneously to understand the effects of allelopathy or in fact any form of competition. Chromatography is traditionally coupled to MS for untargeted metabolomics studies. While coupling chromatography to MS greatly enhances metabolome analysis due to the orthogonality of the techniques, the lengthy analysis times pose challenges for large metabolomics studies. Consequently, there is still a need for developing higher throughput MS approaches. A rapid metabolic fingerprinting method that utilizes a new transmission mode direct analysis in real time (TM-DART) ambient sampling technique is presented in Chapter 5. The optimization of TM-DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. In terms of reproducibility, TM-DART compared favorably with traditional probe mode DART analysis, with coefficients of variation as low as 16%. TM-DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera and was adapted for exhaled breath condensate (EBC) analysis. To determine the feasibility of utilizing TM-DART for metabolomics investigations, TM-DART was interfaced with traveling wave ion mobility spectrometry (TWIMS) time-of-flight (TOF) MS for the analysis of EBC samples from cystic fibrosis patients and healthy controls. TM-DART-TWIMS-TOF MS was able to successfully detect cystic fibrosis in this small sample cohort, thereby, demonstrating it can be employed for probing metabolome changes. Finally, in Chapter 6, a perspective on the presented work is provided along with goals on which future studies may focus.

Indiana University-Purdue University Indianapolis (IUPUI) / The fragmented bodies and lives of postcolonial Caribbean women examined in Caribbean literature beget struggle and psychological ruin. The characters portrayed in novels by postcolonial Caribbean writers Edwidge Danticat, Michelle Cliff, and Shani Mootoo are marginalized as “Other” by a Western patriarchal discourse that works to silence them because of their gender, color, class, and sexuality. Marginalization participates in the act of fragmentation of these characters because it challenges their sense of identity. Fragmentation means fractured; in terms of these fictive characters, fragmentation results from multiple traumas, each trauma causing another break in their wholeness. Postcolonial scholars have identified the causes and effects of fragmentation on the postcolonial subject, and they argue one’s need to heal because of it. Danticat, Cliff, and Mootoo prove that wholeness is not possible for the postcolonial Caribbean woman, so rather than ruminate on that truth, they examine the journey of the postcolonial Caribbean woman as a way of making meaning of the pieces of her life. This project contends that fragmentation – and the fracture it produces – does not bind these women to negative existences; in fact, the female subjects of Danticat, Cliff, and Mootoo locate power in their fragmentation. The texts studied include Danticat’s "Breath, Eyes, Memory" (1994) and "The Farming of Bones" (1999), Cliff’s "Abeng" (1984) and "No Telephone to Heaven" (1987), and Mootoo’s "Cereus Blooms at Night" (1996) and "He Drown She in the Sea" (2005).