In this dissertation, theoretical, computational, and experimental methodologies are introduced to determine the rate-dependent material properties of the brain tissue. Experiments have shown that the brain tissue is significantly rate-dependent. To examine the range of strain rates at which trauma might happen, a validated finite element (FE) human head model was initially employed to examine the biomechanics and dynamic behavior of the head and brain under impact and blast loads. The strain rates to cause traumatic brain injury (TBI) were found to be in the range of 36 to 241 1/s, under these types of loadings. These findings provided a good estimation prior to exploring the required experiments for characterizing the brain tissue. The brain samples were tested by employing unconfined compression tests at three different deformation rates of 10 (n= 10 brain samples), 100 (n=8), and 1000 mm/sec (n=12). It was found that the tissue exhibited a significant rate-dependent behavior with various compression rates. Two different material characterization approaches were proposed to evaluate the rate-dependent mechanical responses of the brain. In the first approach, based on the parallel rheological framework, a single-phase viscoelastic model which captures the key aspects of the rate-dependency in large strain behavior was introduced. The extracted material parameters showed an excellent constitutive representation of tissue response in comparison with the experimental test results (R^2=0.999). The obtained material parameters were employed in the FE simulations of the brain tissue and successfully verified by the experimental results. In the second approach, the brain tissue is modeled as a biphasic continuum, consisting of a compressible solid matrix fully saturated with an incompressible interstitial fluid. The governing equations based on conservation of mass and momentum are used to describe the solid-fluid interactions. This viscoelastic biphasic model can effectively estimate the rate-dependent tissue deformations, the hydrostatic pressure as well as fluid diffusion through the tissue. Although both single-phasic, as well as bi-phasic models, can successfully capture the key aspects of the rate-dependency in large strain deformation, it was shown the biphasic model can demystify more phenomenological behavior of this tissue that could not be perceived with yet established, single-phasic approaches.

The biphasic cuirass ventilation (BCV) device is an alternative respiratory support device for patients with chronic respiratory failure. Considered by some a “forgotten” mode of supportive ventilation, the device is portable, lightweight, and easy to operate. Biphasic cuirass ventilation can also be used to rapidly resuscitate patients in acute respiratory distress and requires minimal technical skill to operate. Biphasic cuirass ventilation can be employed by the patient’s caregiver in the home setting, making it a viable alternative to other forms of mechanical ventilation (e.g., BiPAP) for patients enrolled in home hospice or palliative care. The article reviews current knowledge and aims to enhance awareness and encourage further study about cuirass ventilation, particularly with regard to its use in treating patients in the palliative care setting and in the home.

Hormesis is a nonlinear dose-response characterized by biological responses at low doses that are opposite to those observed at higher doses. Studies and review articles on hormesis are being published at an increasing rate by researchers from diverse disciplines and debate has emerged over the role hormesis in risk assessment. As a result, a survey was conducted to assess toxicologists and risk assessors knowledge and attitudes about the hormesis dose response. Study goals were to: 1) ascertain attitudes towards hormesis and other dose-response models, 2) identify whether acceptance or rejection of hormesis is based on knowledge of hormesis, predisposing values, or demographic characteristics, and 3) evaluate potential for response bias. The survey consisted of 44 questions pre-tested by 25 toxicologists and risk assessors. The survey was distributed via email to the membership of the Society of Toxicology and the Society for Risk Analysis, 9,500 potential respondents. The overall response rate was 17% (n= 1,463) with a completion rate over 87%. Major findings were that 50% of respondents indicated sufficient data exist to support the view hormesis occurs across a wide range of species and endpoints, 59% indicated evaluating potential benefits due to hormesis should be included in risk assessments, and 65% are in favor of modifying hazard assessment protocols to identify the presence of hormesis. Respondent characteristics such as: years of experience, society membership, education, residence, employment (excluding government and pharmaceutical companies), and political, economic or social views had little influence on opinion. One of the largest positive influences was experience with hormesis based on actual research; 79% of subjects who reported observing hormesis commonly in their studies agreed hormesis is broadly generalizable. The influence of non-response bias was evaluated through several internal and external measures. Despite a lower than hoped for response rate, but because of robust external validity measures, it is concluded that respondents’ opinions are likely a reasonable representation of the societies of which they are members. Because this is a baseline survey, a follow-up survey is in order. Future survey design should separately evaluate the science of dose-response from the regulatory approach to risk assessment.

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No / The isotopic effect of exchanging deuterium with hydrogen on the mechanical and surface properties of agar gel is examined. The elastic modulus of the D2O gels obtained by AFM nanoindentation is significantly higher (factor of 1.5¿2) than the modulus found in H2O agar gels. Furthermore, the modulus is independent of loading rate. Surface imaging reveals that the surface roughness gets progressively smaller with increasing agar concentration. All these data suggest that the isotopic replacement of deuterium enhances the mechanical properties of the agar gel, with significant advantages in its use as a biphasic scaffold. / MRC

The genus <i>Gluconobacter</i> is known to carry out limited oxidations using the NAD(P)-independent membrane-bound dehydrogenases in which the products are released back to the medium. Reports of further limited oxidations of these primary oxidation products by <i>Gluconobacter</i> in single step or sequential oxidations by secondary dehydrogenases are also published. The objective of this project was to evaluate the nature of one primary (sorbitol) dehydrogenase and one secondary (sorbose) dehydrogenase because of their importance in Vitamin C production. My hypotheses were that sorbitol (the primary) dehydrogenase is constitutive, while sorbose (the secondary) dehydrogenase is inducible. Six <i>Gluconobacter</i> strains from three different species grew on plates containing 50/0 sorbose, indicating their ability to oxidize sorbose thus possessing a secondary dehydrogenase. When four strains were tested for their ability to carry out the sequential oxidation of sorbitol and then sorbose on media containing growth-limiting sorbitol concentrations, three strains showed possible biphasic growth. However, thin layer chromatography of culture media did not support sequential sorbitol and sorbose oxidation. F erricyanide assays for sorbitol and sorbose dehydrogenases from membrane fractions isolated from cells grown on glycerol, sorbitol, or sorbose showed that sorbitol dehydrogenase activity in all four strains (three species) tested was always present (constitutive) and its specific activity was always enhanced by growth on sorbose. Membrane fractions showed no or very low constitutive sorbose dehydrogenase activity and no evidence that this secondary dehydrogenase was induced. / Master of Science

Yes / Highly-branched poly(N-isopropyl acrylamide)s in water pass through coil-to-globule transitions. Using calorimetry and the colour change of a solvatochromic dye within the polymer, we show that some compositions have biphasic core–shell morphologies, with globular cores and open coil shells. The two-phase structure is favoured by increased branching and arises because the chain ends penetrate only to a limited degree into the polymer coil.

O objetivo deste trabalho foi à purificação da toxina alfa produzida por Costridium perfringens tipo A em sistema de duas fases aquosas (SDFA) PEG/fosfato nos modos contínuo e descontínuo. Dois planejamentos fracionários sequenciais foram aplicados para estudar a partição da toxina alfa em SDFA, em função de 4 variáveis: massa molar e concentração do PEG, concentração do fosfato e pH. Os melhores resultados para o fator de purificação, rendimento em atividade e coeficiente de partição foram obtidos com PEG 8000 g/mol (15%, w/w), fosfato 20% (w/w) e pH 8.0. Este sistema permitiu um fator de purificação de 4,6 com rendimento em atividade de 230% e coeficiente de partição de 113,9 na fase PEG. Após isto, novos experimentos foram realizados para aperfeiçoar a purificação da toxina alfa com o emprego de um planejamento experimental completo 22. Nesta pesquisa a concentração do PEG 8000 g/mol e sais de fosfato pH 8,0 foram variados. O coeficiente de partição, fator de purificação e rendimento em atividade foram fortemente influenciados por estas variáveis. Aumentando ambos os fatores estudados, foi observado um aumento nas respostas, com exceção para o fator de purificação. O melhor fator de purificação (5,7) foi obtido com 17,5% e 15% das concentrações de PEG e fosfato, respectivamente. A coluna de discos perfurados rotativos (PRDC) foi usada para extrair toxina alfa a partir do sobrenadante com (PEG) (MM = 8,000 g/mol) e solução de sais de fosfato de sódio e de potássio (pH 8.0). Os resultados obtidos demonstraram que a velocidade de fluxo da fase dispersa (VD) de 3 Ml/min foi a melhor condição para as respostas hold up (ED = 0,8), eficiência de separação (ES = 100 %) e fator de purificação (Pf = 2,37), pois os melhores resultados foram obtidos nesta taxa de fluxo usando uma velocidade de rotação dos discos baixa (35 rpm), enquanto o melhor coeficiente de transferência de massa (KDa = 2,8 x10-3 min-1) foi encontrado na maior velocidade de rotação usada (140 rpm). / The aim this work was purification alpha-toxin (phospholipase C) produced by Costridium perfringens type A by aqueous two-phase systems (ATPS) PEG/phosphate in discontinue and continue mode. Two sequential half-fraction designs were applied to studying the &#8733;-toxin partition in ATPS, as a function of four factors: PEG molar mass and concentration, phosphate concentration and pH. The highest purification factor, yield and partition coefficient results were obtained with PEG 8000 (15%, w/w), phosphate at 20% (w/w) and pH 8.0. This system allows an &#8733;-toxin purification of 4.6 fold with final activity yield of 230% and partition coefficient of 113.9 in the PEG rich phase. After this, new experiments were realized for the optimization of &#8733;-toxin purification with employed of full experimental design. In this research the concentration of PEG 8000 g/mol and phosphate salts pH 8.0 were varied. The partition coefficient (K), purification factor (Pf) and activity yield (Y%) were strongly influenced for these variables. Increasing both factors was observed an increase of these responses, except for P Pf. The higher purification factor (5.7) was obtained with 17.5% and 15% of the PEG and phosphate concentration, respectively. A continuous perforated rotating disc contactor (PRDC) was used for extraction of &#8733;-toxin from the supernatant of Clostridium perfringens type A cultivations with polyethylene glycol (PEG) (MW = 8,000 g/mol) and dipotassium and sodium phosphate salt solution (pH 8.0). The results obtained demonstrated that VD = 3 L/min was by far the optimum dispersed phase flowrate for all these response variables. Besides, maximum values of ED (0.8), Es (100 %) and Pf (2.37) were obtained at this flowrate using the lowest rotational speed (35 rpm), while optimum KDa (2.8 x 10-3 min-1 ) was achieved at the highest agitation level (140 rpm).

O objetivo deste trabalho foi à purificação da toxina alfa produzida por Costridium perfringens tipo A em sistema de duas fases aquosas (SDFA) PEG/fosfato nos modos contínuo e descontínuo. Dois planejamentos fracionários sequenciais foram aplicados para estudar a partição da toxina alfa em SDFA, em função de 4 variáveis: massa molar e concentração do PEG, concentração do fosfato e pH. Os melhores resultados para o fator de purificação, rendimento em atividade e coeficiente de partição foram obtidos com PEG 8000 g/mol (15%, w/w), fosfato 20% (w/w) e pH 8.0. Este sistema permitiu um fator de purificação de 4,6 com rendimento em atividade de 230% e coeficiente de partição de 113,9 na fase PEG. Após isto, novos experimentos foram realizados para aperfeiçoar a purificação da toxina alfa com o emprego de um planejamento experimental completo 22. Nesta pesquisa a concentração do PEG 8000 g/mol e sais de fosfato pH 8,0 foram variados. O coeficiente de partição, fator de purificação e rendimento em atividade foram fortemente influenciados por estas variáveis. Aumentando ambos os fatores estudados, foi observado um aumento nas respostas, com exceção para o fator de purificação. O melhor fator de purificação (5,7) foi obtido com 17,5% e 15% das concentrações de PEG e fosfato, respectivamente. A coluna de discos perfurados rotativos (PRDC) foi usada para extrair toxina alfa a partir do sobrenadante com (PEG) (MM = 8,000 g/mol) e solução de sais de fosfato de sódio e de potássio (pH 8.0). Os resultados obtidos demonstraram que a velocidade de fluxo da fase dispersa (VD) de 3 Ml/min foi a melhor condição para as respostas hold up (ED = 0,8), eficiência de separação (ES = 100 %) e fator de purificação (Pf = 2,37), pois os melhores resultados foram obtidos nesta taxa de fluxo usando uma velocidade de rotação dos discos baixa (35 rpm), enquanto o melhor coeficiente de transferência de massa (KDa = 2,8 x10-3 min-1) foi encontrado na maior velocidade de rotação usada (140 rpm). / The aim this work was purification alpha-toxin (phospholipase C) produced by Costridium perfringens type A by aqueous two-phase systems (ATPS) PEG/phosphate in discontinue and continue mode. Two sequential half-fraction designs were applied to studying the &#8733;-toxin partition in ATPS, as a function of four factors: PEG molar mass and concentration, phosphate concentration and pH. The highest purification factor, yield and partition coefficient results were obtained with PEG 8000 (15%, w/w), phosphate at 20% (w/w) and pH 8.0. This system allows an &#8733;-toxin purification of 4.6 fold with final activity yield of 230% and partition coefficient of 113.9 in the PEG rich phase. After this, new experiments were realized for the optimization of &#8733;-toxin purification with employed of full experimental design. In this research the concentration of PEG 8000 g/mol and phosphate salts pH 8.0 were varied. The partition coefficient (K), purification factor (Pf) and activity yield (Y%) were strongly influenced for these variables. Increasing both factors was observed an increase of these responses, except for P Pf. The higher purification factor (5.7) was obtained with 17.5% and 15% of the PEG and phosphate concentration, respectively. A continuous perforated rotating disc contactor (PRDC) was used for extraction of &#8733;-toxin from the supernatant of Clostridium perfringens type A cultivations with polyethylene glycol (PEG) (MW = 8,000 g/mol) and dipotassium and sodium phosphate salt solution (pH 8.0). The results obtained demonstrated that VD = 3 L/min was by far the optimum dispersed phase flowrate for all these response variables. Besides, maximum values of ED (0.8), Es (100 %) and Pf (2.37) were obtained at this flowrate using the lowest rotational speed (35 rpm), while optimum KDa (2.8 x 10-3 min-1 ) was achieved at the highest agitation level (140 rpm).