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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
81

Chloride Ingress into Submerged Concrete Under Sustained Load

Karam, Andrew 24 January 2014 (has links)
A harsh, cold, and icy environment is of no surprise to the conditions of a winter climate, where the wide use of de-icing salts on roads and highways allows for the initiation of chloride-induced corrosion of the reinforcement of concrete structures; a reduced service life, loss of structural integrity, visible damages, and ultimately structural failure are among the many unwanted effects of rebar corrosion. Chloride ingress into concrete has been extensively studied for the last four decades; however, most of the relevant research to date does not take into account the effects of sustained loading on chloride transport properties. Therefore, the objectives of this study were to investigate the influence of sustained compressive and tensile stresses on chloride ingress into concrete, and ultimately to understand what the effect of sustained stress is on chloride penetration depth, on chloride concentration by % weight of concrete, and on apparent diffusion coefficients by comparing results to those of unloaded control specimens. To achieve these objectives, six post-tensioned and four non-reinforced control concrete beams were constructed with different water-to-cement (w/c) ratios and completely submerged in a 4-5% de-icing salt (NaCl) solution for 12 weeks, allowing chloride transfer to be completely governed by continuous diffusion. The effects of supplementary cementing material on chloride ingress are also studied. Concrete beams were post-tensioned to induce variable sustained compressive and tensile stresses along the beam. After 12 weeks of exposure, beams were fractured at specific locations and sprayed with a 0.1N silver nitrate (AgNO3) solution to determine average penetration depths; chloride concentration profiles were obtained from potentiometric titration of grinded powder samples. Apparent chloride diffusion coefficients were then obtained from the results of spraying AgNO3 and titration, the latter by non-linear regression curve-fitting to Fick’s second law of diffusion. A good agreement between results from both methods reveals that the use of AgNO3 in field is acceptable in predicting the rate of chloride ingress in concrete sustaining stress. The chloride diffusivity for each profile, relative to that of the unstressed section, was related to the compressive and tensile stresses in the concrete section. The experimental results indicate the dependence of chloride ingress and concentration on the type and level of sustained stress. An analysis of the results to study the effects of the w/c ratio using colourimetric (silver nitrate spray) and potentiometric titration methods was also completed.
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82

Numerical Investigation Of Incompressible Flow In Grooved Channels- Heat Transfer Enhancment By Self Sustained Oscillatins

Gurer, Turker 01 April 2003 (has links) (PDF)
In this study, forced convection cooling of package of 2-D parallel boards with heat generating chips is investigated. The main objective of this study is to determine the optimal board-to-board spacing to maintain the temperature of the components below the allowable temperature limit and maximize the rate of heat transfer from parallel heat generating boards cooled by forced convection under constant pressure drop across the package. Constant heat flux and constant wall temperature boundary conditions on the chips are applied for laminar and turbulent flows. Finite elements method is used to solve the governing continuity, momentum and energy equations. Ansys-Flotran computational fluid dynamics solver is utilized to obtain the numerical results. The solution approach and results are compared with the experimental, numerical and theoretical results in the literature. The results are presented for both the laminar and turbulent flows. Laminar flow results improve existing relations in the literature. It introduces the effect of chip spacing on the optimum board spacing and corresponding maximum heat transfer. Turbulent flow results are original in the sense that a complete solution of turbulent flow through the boards with discrete heat sources with constant temperature and constant heat flux boundary conditions are obtained for the first time. Moreover, optimization of board-to-board spacing and maximum heat transfer rate is introduced, including the effects of chip spacing.
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83

Early Indicators of Executive Function and Attention in Preterm and Full-term Infants

Sun, Jing (Jenny) January 2003 (has links)
This study investigated executive function and sustained attention in preterm and full-term infants at 8 months after expected date of delivery and at 10-11 months chronological age. Executive function and sustained attention emerge in infancy and continues to develop throughout childhood. Executive function and sustained attention is believed to underlie some learning problems in children at school age. Although numerous studies have reported that the overall development of preterm infants is comparable to that of full-term infants at the same corrected age, it is unclear to what extent the development of specific cognitive abilities is affected by prematurity and/or other factors such as medical complications. As preterm infants have a high rate of learning difficulties, it is possible that factors associated with prematurity specifically affect the development of some regions of the brain associated with the regulation of executive function and sustained attention. Thirty-seven preterm infants without identified disabilities, and 74 due date and gender matched healthy bull-term infants, participated in the present study. The preterm infants were all less that 32 weeks gestation and less that 1500 grams birth weight. The current study aimed to examine the effects of maturation and length of exposure to extrauterine environmental stimuli on the development of executive function and sustained attention, by comparing the development of preterm infants with that of full-term infants at both the same corrected age and the same chronological age. All infants were therefore assessed on executive function and sustained attention tasks at 8 months after the expected date of delivery (when preterm infants were actually 10-11 months chronological age). The full-term infants in the study were then reassessed at an age equivalent to the chronological age of their matched preterm infants at the time of the first assessment. The findings of the study showed that preterm infants performed significantly more poorly than full-term infants at both 8 months after the expected date of delivery and 10-11 months chronological age on all measures of executive function and sustained attention. However the difference between preterm and full-term infants at 8 months after expected date of delivery was much less that at 10-11 months chronological age. The results suggested that the effects of maturation are greater that the effects of exposure to extrauterine environmental stimuli on the development of executive function and sustained attention. However, as the performance of the preterm infants was below that of the term infants at the same corrected age, it was necessary to consider whether other factors associated with preterm birth were contributing to this difference. Confounding factors including cognitive abilities and psychomotor skills on the Bayley Scales of Infant Development, infant temperament, maternal education, family socioeconomic status and maternal psychological wellbeing were examined. Statistical analysis of the effects of these factors on the difference between preterm ad full-term infants found that only psychomotor sills significantly affected the differences between preterm and full-term infants of the same corrected age on executive function measures, although not on sustained attention measures. The differences between preterm and full-term infants of the same corrected age remained even when psychomotor skills were taken into consideration; therefore psychomotor skills were not sufficient to fully explain the differences between preterm and full-term infants in the performance of executive function. Consequently, the preterm infants were divided into two subgroups on the basis of (a) low or high medical risk factors, (b) birth weight of less that 1000g versus 1000-1500g, and (c) gestation age of less that 28 weeks versus 28-32 weeks, in order to assess the effects of these variables on the performance of executive function and sustained attention. Medical risk, lower birth weight and lower gestation age were all found to adversely affect performance on executive function, but did not affect the performance on sustained attention tasks. It is argued that these factors may influence the development of specific areas of the brain which govern executive function, and that as the prefrontal regions are particularly immature they may be especially vulnerable to damage or disruption. The fact that these perinatal factors did not contribute to the difference between preterm and full-term infants' performance on sustained attention tasks. This suggests that the deficits of sustained attention in preterm infants may be associated with birth prematurity per se, and that additional complications may not have any further detrimental effect. The three components of executive function (i.e., working memory, inhibition, and planning) did not correlate with each other when only infants with Bayley psychomotor ability scores greater that 85 were included, suggesting that the components of executive function may be discrete abilities which are governed by different parts of the prefrontal cortex. Sustained attention correlated with planning, supporting the suggestion that it may be a cognitive dimension which overlaps with executive function, depending upon the task requirement. Neither executive functio nor sustained attention correlated with the Bayley mental ability and Bayley psychomotor ability scores when infants with scores of less than 85 were excluded. This suggests that executive function and sustained attention measures are independent of general development.
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84

Farmacocinética do cloridrato de tramadol administrado por via oral em cães com a mutação nt230(del4) no gene MDR1

Baja, Karine Gehlen January 2013 (has links)
A P-glicoproteína (P-gp) é uma transportadora transmembrana de múltiplos fármacos, produto do gene MDR1 (ABCB1). A P-gp contribui para a função de barreira de vários tecidos e órgãos, funcionando como uma bomba de efluxo para muitos substratos. Diminuição na expressão desta proteína é associada à sensibilidade a fármacos. Cães da linhagem dos Collies possuem uma alta incidência de uma mutação no gene MDR1, denominada nt230(del4). Animais homozigotos para a mutação apresentam a supressão total de uma P-gp funcional e um animal heterozigoto apresenta uma maior sensibilidade para substratos da P-gp, devido a uma diminuição na expressão da mesma. Alguns fármacos opioides, como a morfina e a metadona, foram identificados como substratos da P-gp. O tramadol é um dos analgésicos opioides mais utilizados em cães. No presente trabalho, a mutação MDR1 nt230(del4) foi analisada em vinte cães Collie, utilizando reação em cadeia de polimerase (PCR). A identificação foi realizada por eletroforese em gel de poliacrilamida de alta resolução, sendo o resultado confirmado por análise de sequênciamento de DNA. Como resultado, seis cães apresentaram normalidade nos dois alelos e 14 apresentaram heterozigose para a mutação. Estes animais foram submetidos à segunda fase do experimento, quando se administrou uma dose única de 100 mg de tramadol oral de liberação prolongada (SR), objetivando investigar o tramadol como sendo substrato da P-gp. Outro objetivo foi avaliar a farmacocinética deste tipo de formulação, pois ainda não foi estabelecida para cães. A análise farmacocinética do tramadol foi realizada utilizando cromatografia líquida de alta eficiência (CLAE) com detecção por espectrometria de massas para a determinação e quantificação de tramadol no soro canino. O analito e o padrão interno foram extraídos do soro por método líquido-líquido. A separação cromatográfica foi obtida a partir de uma coluna analítica C18, mantida a 30°C, sob condições isocráticas de uma fase móvel constituída por uma mistura de acetonitrila e ácido fórmico a 0,1% (80:20). A concentração de tramadol no soro foi maior do que o limite de quantificação (LOQ), em 17 cães. Os cães foram divididos em dois grupos, cães normais (MDR1 +/+) e heterozigotos (MDR1 +/-). Os cálculos farmacocinéticos para o tramadol oral SR obtiveram valores médios de concentração máxima no soro (Cmax) de 63,12 ng/mL ± 33,35 para o grupo normal e 58,00 ng/mL ± 27,29 para o grupo heterozigoto. Tmax (tempo de concentração plasmática maxima) foi de 4 h para ambos os grupos e t ½ (meia-vida) foram 2,85 h ± 1,61 e 2,81 ± 1,46 h para os cães normais e heterozigotos, respectivamente. A área sob a curva (AUC) média para o tramadol oral SR para o grupo normal e heterozigoto foram 350,20 ± 216,61 e 312,15 ± 155,43 ng.h/mL, respectivamente. A biodisponibilidade foi de 22% e 23% para os cães normais e heterozigotos, respectivamente. Não houve diferença estatística entre os grupos em todos os parâmetros farmacocinéticos. Os resultados sugerem que o tramadol não é um substrato da Pgp. A quantidade de dados farmacocinéticos do tramadol oral na formulação de liberação prolongada (SR) em cães é escassa, sendo necessários mais estudos farmacocinéticos e farmacodinâmicos para o tramadol oral de liberação prolongada em cães para estabelecer adequada dose e frequência de administração em cães. / The P-glycoprotein (P-gp) is a transmembrane multidrug transporter, product of the MDR1 (ABCB1) gene. P-gp contributes to the barrier function of several tissues and organs, acting as an efflux pump for many substrates. Decreased expression of this protein is associated with sensitivity to drugs. Collie dogs have a high incidence of a mutation in MDR1 gene, denominated MDR1 nt230 (del4). In homozygosis, this mutation results in the total absence of a functional P-gp and a heterozygote animal presents a greater sensibility to P-gp substrates, probably due to a decrease in the expression thereof. Some opioid drugs such as morphine and methadone were identified as P-gp substrates. Tramadol is one of the most commonly opioid used in dogs. In the present work MDR1nt230 (del4) mutation was analyzed in 20 healthy Collie dogs using allele-specific polymerase chain reaction (PCR) method. Thereby, 6 homozygous intact and 14 heterozygous mutated MDR1 genotypes can be differentiated by high resolution polyacrylamide gel electrophoresis, confirmed by DNA sequence analysis. These animals underwent the second phase of the experiment, when a single oral administration of 100 mg of sustained release (SR) tramadol was administrated to investigate the tramadol as P-gp substrate. In addition, another aim was evaluate the pharmacokinetics of sustained release formulation, which has not been established for dogs. Pharmacokinetic analysis of tramadol was evaluated using high performance liquid chromatography (HPLC) with tandem mass spectrometry for determination and quantification of tramadol in canine serum. The analyte and internal standard (IS) were extracted from serum using liquid-liquid method. Chromatographic separation was achieved on a C18 analytical column, kept at 30°C, under isocratic conditions of a mobile phase consisted by a mixture of acetonitrile and water contained 0,1% formic acid (80:20). Serum tramadol concentration was greater than the limit of quantification (LOQ) in 17 dogs. The dogs were divided into two groups, normal dogs (MDR1 +/+) and heterozygous (MDR1 +/-) according to the MDR1 genotype. The median values of maximum serum concentration (Cmax) were 63.13 ng/mL ± 33.35 for the normal group and 58.01 ng/mL ± 27.29 for the heterozygous group. Tmax (time to maximum serum concentration) was 4 h for both groups and t ½ (half-life) were 2,85h ± 1,61 e 2,81h ± 1,46 for normal and heterozygous dogs, respectively. The mean area-under-the-curve (AUC) values for the sustained release tramadol compounds for the normal and heterozygous group were 350,20 ±216,61 and 312,15 ± 155,43 ng.h/mL, respectively. The bioavailability was 22% and 23% for normal and heterozygous dogs respectively. There was no statistic difference between groups in all pharmacokinetics parameters. The findings suggest that tramadol is not a P-gp substrate. The amount of pharmacokinetics data of SR formulation of tramadol in dogs is sparse. Therefore, more studies of oral SR tramadol in dogs are needed to establish appropriate dose and frequency of administration in dogs.
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85

Revestimento de grânulos farmacêuticos em leito fluidizado / Fluidized bed coating of pharmaceutical granules.

Fabiano de Araújo Rezende 22 October 2007 (has links)
Operações de revestimento são amplamente utilizadas em diversos setores industriais, tais como químico, agrícola, alimentício e farmacêutico. Dentre as principais razões para a aplicação de revestimento em partículas destacam-se fatores estéticos, proteção e o controle da taxa de dissolução de substâncias químicas. Este trabalho teve por objetivo investigar o revestimento de sólidos farmacêuticos em leito fluidizado. Inicialmente foram realizados ensaios fluidodinâmicos visando à definição de parâmetros operacionais nos quais ocorre uma operação estável do sistema. Definidas condições de operação estável, realizaram-se ensaios de revestimento de grânulos contendo um fármaco modelo (paracetamol), empregando-se uma composição à base de Eugradit RS30D. Nesta etapa investigou-se a influência da vazão de ar de fluidização, do diâmetro das partículas, da temperatura do ar de fluidização e da vazão de suspensão de revestimento na fração revestida, Wrt; na eficiência do revestimento, ; e no índice de aglomeração, Agl. Ensaios de liberação in vitro foram realizados no sentido de se avaliar a alteração das propriedades de liberação do fármaco devido ao revestimento aplicado. Os resultados obtidos evidenciaram que um tempo maior de processo levou à formação de um filme de revestimento mais espesso, modificando o perfil de dissolução do fármaco. Amostras de grânulos revestidos em condições selecionadas foram submetidas a um tratamento térmico, que consistiu na armazenagem do produto em estufa à 40 oC por intervalos de tempo que variaram de 1 a 96 horas sendo, posteriormente, realizados ensaios de dissolução. Verificouse que, nas condições experimentais utilizadas, o tratamento térmico do grânulo revestido não influenciou na velocidade liberação do fármaco, independentemente do período de armazenagem. / Coating operations are widely used in several industrial sectors, such as the chemical, agricultural, food and pharmaceutical. Among the reasons for particle coating application, the aesthetic, protection against the environment and the control of the dissolution rate of chemical substances are prominent. The aim of this work was to investigate the fluidized bed coating of pharmaceutical solids. Initially, hydrodynamic tests were carried out in order to define the operating parameters which lead to a stable system operation. After selection of the conditions of stable operation, coating experiments of granules containing a model drug (acetaminophen), with a coating composition based on Eudragit RS30D were started. In this stage, it was investigated the effects of the flow rate of the fluidizing air, mean particle diameter, inlet temperature of the fluidizing air, and the feed flow rate of the coating suspension on the coating fraction, Wrt; on coating efficiency, ; and on agglomerating index, Agl. In vitro dissolution tests were performed to evaluate the modification of the drug release properties due to the coating application. The results showed that the thickness of the coating layer is dependent of the processing time, leading to a modification on drug release profiles. Samples of the coated granules obtained at selected conditions were submitted to a thermal treatment, which consisted of the product storage in an air circulated oven at 40 oC during 1 to 96 hours time intervals. After the thermal treatment the granules were submitted to dissolution tests. It was verified, in the experimental conditions used, that the thermal treatment of the coated granules do not influenced the drug release rate, independently of the storage period.
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86

Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla / Influence of inflamatory response on sustained virological response in pa ents with chronic Hepa s C genotype 1 during an viral treatment with triple therapy

Winckler, Fernanda Cristina [UNESP] 19 October 2016 (has links)
Submitted by FERNANDA CRISTINA WINCKLER null (fwinckler@fmb.unesp.br) on 2016-11-30T19:00:44Z No. of bitstreams: 1 DISSERTAÇÃO FINAL 30.11.16.pdf: 468887 bytes, checksum: 372ef2c27b73313e5608616205ed1d2e (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-12-02T16:28:26Z (GMT) No. of bitstreams: 1 winckler_fc_me_bot.pdf: 468887 bytes, checksum: 372ef2c27b73313e5608616205ed1d2e (MD5) / Made available in DSpace on 2016-12-02T16:28:26Z (GMT). No. of bitstreams: 1 winckler_fc_me_bot.pdf: 468887 bytes, checksum: 372ef2c27b73313e5608616205ed1d2e (MD5) Previous issue date: 2016-10-19 / A hepatite C é uma doença infecciosa que torna-se crônica em cerca de 85% dos infectados que poderão desenvolver cirrose e carcinoma hepato celular. O tratamento antiviral em muitos dos pacientes não é eficaz, principalmente quando estes portam o genótipo 1 e fibrose avançada, a resposta inflamatória também desempenha seu papel sobre a resposta virológica sustentada (RVS) durante o tratamento com Interferon Peguilado (PegIFN) associado a Ribavirina (RBV). Nesse estudo nosso objetivo principal foi avaliar a influência da resposta inflamatória através de células e citocinas/quimiocinas sobre a resposta virológica do paciente em tratamento antiviral com terapia tripla. Incluimos pacientes com RNA VHC+, nunca tratados (naive), portadores do genótipo 1, ambos os sexos e com fibrose avançada F3 (n=6); F4 (n=21) candidatos ao tratamento em regime triplo. Os pacientes tiveram suas amostras coletadas e analizadas nas semanas 0 e 12 do tratamento e os seguintes parâmetros foram analisados: IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ, RANTES, MCP-1, MIG, IP- 10, através de citometria de fluxo (método CBA). Foram incluídos 15 voluntários saudáveis (grupo controle) e 27 pacientes que foram separados em G1(RVS) e G2 (não RVS), a taxa de RVS foi de 63%. Os pacientes com hepatite C crônica tiveram os níveis circulantes de IP10, MCP-1, MIG, RANTES, IL-8 e IL-6 mais elevados quando comparados com voluntários saudáveis, quando comparados G1xG2 os níveis de RANTES (p=0,04) e IL-6 (p=0,02) foram associadas com a RVS na semana 0, seus níveis eram mais baixos em G1, na semana 12 os níveis de RANTES (p=0,04) e IL-8 (n=0,01) foram associados com a RVS, seus níveis são mais elevados em G2, a comparação entre as semanas 0 e 12 mostrou que em G1 os níveis de IL6 (p= 0,02) e MCP-1 (p=0,001) apresentam associação com o tratamento e em G2 os parâmetros associados ao tratamento foram RANTES (p=0,05) e MCP-1 (p=0,01). Os resultados sugerem que, a citocina IL-6 e a quimiocina RANTES estão associadas com a RVS na semana 0. Na semana 12, RANTES assim como IL-8 influenciam na RVS durante terapia antiviral em regime triplo. Quando comparado semana 0 e 12 em pacientes RVS, a citocina IL-6 está associada ao tratamento. Em pacientes não RVS, RANTES esta associada ao tratamento e MCP-1 está associada ao tratamento independente da resposta obtida. / Hepatitis C is an infectious disease which becomes chronic in about 85% of infected people who can develop cirrhosis and hepatocellular carcinoma. Antiviral therapy isn’t effective in many patients, especially when these patients are genotype 1 and have advanced fibrosis, the inflammatory response also plays a role on sustained virological response (SVR) during treatment with Pegylated (PegIFN) plus Ribavirin (RBV). The aim of this study was evaluate the influence of the inflammatory response by cells and cytocines/chemokines on the virologic response of the patients under antiviral treatment with triple therapy. We included patients with HCV RNA+, naive, genotype 1, both male and female and with advanced fibrosis F3 (n=6); F4 (n=21) for triple treatment regimen. Patients had their samples collected and analyzed at weeks 0 and 12 of treatment and the following parameters were analyzed: IL- 2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ RANTES, MCP-1, MIG, IP-10 by flow cytometry (CBA method). Control group of 15 healthy volunteers and 27 patients, who were separated into GI (SVR) and G2 (not SRV), were included, the SVR rate was 63%. Patients with chronic hepatitis C had higher circulating levels of IP10, MCP-1, MIG, RANTES, IL-8 and IL-6 compared with healthy volunteers, when G1xG2 were compared, levels of RANTES (p=0,040 and IL-6 (n=0,02) were associated with a SVR at week 0 and its levels were lower in G1; at week 12, levels of RANTES (p=0,04) and IL-8 (p=0,01) were associated with a SVR and its levels were higher in G2. The comparison between weeks 0 and 12 showed that, in G1, the IL6 levels (p = 0.02) and MCP-1 (p = 0.001) were associated with the treatment and in G2, the parameters associated with the treatment were RANTES (p = 0.05) and MCP-1 (p = 0.01). The results suggest that the cytocine IL-6 and chemokine RANTES are associated with SVR at week 0. At week 12, RANTES as well as IL-8 influence in SVR during antiviral therapy in triple regimen. When weeks 0 and 12 in patients SVR are compared, the cytocine IL-6 is associated with treatment. In non-SVR patients, RANTES is associated with treatment and MCP-1 is associated with independent treatment of the patient's response.
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87

Farmacocinética do cloridrato de tramadol administrado por via oral em cães com a mutação nt230(del4) no gene MDR1

Baja, Karine Gehlen January 2013 (has links)
A P-glicoproteína (P-gp) é uma transportadora transmembrana de múltiplos fármacos, produto do gene MDR1 (ABCB1). A P-gp contribui para a função de barreira de vários tecidos e órgãos, funcionando como uma bomba de efluxo para muitos substratos. Diminuição na expressão desta proteína é associada à sensibilidade a fármacos. Cães da linhagem dos Collies possuem uma alta incidência de uma mutação no gene MDR1, denominada nt230(del4). Animais homozigotos para a mutação apresentam a supressão total de uma P-gp funcional e um animal heterozigoto apresenta uma maior sensibilidade para substratos da P-gp, devido a uma diminuição na expressão da mesma. Alguns fármacos opioides, como a morfina e a metadona, foram identificados como substratos da P-gp. O tramadol é um dos analgésicos opioides mais utilizados em cães. No presente trabalho, a mutação MDR1 nt230(del4) foi analisada em vinte cães Collie, utilizando reação em cadeia de polimerase (PCR). A identificação foi realizada por eletroforese em gel de poliacrilamida de alta resolução, sendo o resultado confirmado por análise de sequênciamento de DNA. Como resultado, seis cães apresentaram normalidade nos dois alelos e 14 apresentaram heterozigose para a mutação. Estes animais foram submetidos à segunda fase do experimento, quando se administrou uma dose única de 100 mg de tramadol oral de liberação prolongada (SR), objetivando investigar o tramadol como sendo substrato da P-gp. Outro objetivo foi avaliar a farmacocinética deste tipo de formulação, pois ainda não foi estabelecida para cães. A análise farmacocinética do tramadol foi realizada utilizando cromatografia líquida de alta eficiência (CLAE) com detecção por espectrometria de massas para a determinação e quantificação de tramadol no soro canino. O analito e o padrão interno foram extraídos do soro por método líquido-líquido. A separação cromatográfica foi obtida a partir de uma coluna analítica C18, mantida a 30°C, sob condições isocráticas de uma fase móvel constituída por uma mistura de acetonitrila e ácido fórmico a 0,1% (80:20). A concentração de tramadol no soro foi maior do que o limite de quantificação (LOQ), em 17 cães. Os cães foram divididos em dois grupos, cães normais (MDR1 +/+) e heterozigotos (MDR1 +/-). Os cálculos farmacocinéticos para o tramadol oral SR obtiveram valores médios de concentração máxima no soro (Cmax) de 63,12 ng/mL ± 33,35 para o grupo normal e 58,00 ng/mL ± 27,29 para o grupo heterozigoto. Tmax (tempo de concentração plasmática maxima) foi de 4 h para ambos os grupos e t ½ (meia-vida) foram 2,85 h ± 1,61 e 2,81 ± 1,46 h para os cães normais e heterozigotos, respectivamente. A área sob a curva (AUC) média para o tramadol oral SR para o grupo normal e heterozigoto foram 350,20 ± 216,61 e 312,15 ± 155,43 ng.h/mL, respectivamente. A biodisponibilidade foi de 22% e 23% para os cães normais e heterozigotos, respectivamente. Não houve diferença estatística entre os grupos em todos os parâmetros farmacocinéticos. Os resultados sugerem que o tramadol não é um substrato da Pgp. A quantidade de dados farmacocinéticos do tramadol oral na formulação de liberação prolongada (SR) em cães é escassa, sendo necessários mais estudos farmacocinéticos e farmacodinâmicos para o tramadol oral de liberação prolongada em cães para estabelecer adequada dose e frequência de administração em cães. / The P-glycoprotein (P-gp) is a transmembrane multidrug transporter, product of the MDR1 (ABCB1) gene. P-gp contributes to the barrier function of several tissues and organs, acting as an efflux pump for many substrates. Decreased expression of this protein is associated with sensitivity to drugs. Collie dogs have a high incidence of a mutation in MDR1 gene, denominated MDR1 nt230 (del4). In homozygosis, this mutation results in the total absence of a functional P-gp and a heterozygote animal presents a greater sensibility to P-gp substrates, probably due to a decrease in the expression thereof. Some opioid drugs such as morphine and methadone were identified as P-gp substrates. Tramadol is one of the most commonly opioid used in dogs. In the present work MDR1nt230 (del4) mutation was analyzed in 20 healthy Collie dogs using allele-specific polymerase chain reaction (PCR) method. Thereby, 6 homozygous intact and 14 heterozygous mutated MDR1 genotypes can be differentiated by high resolution polyacrylamide gel electrophoresis, confirmed by DNA sequence analysis. These animals underwent the second phase of the experiment, when a single oral administration of 100 mg of sustained release (SR) tramadol was administrated to investigate the tramadol as P-gp substrate. In addition, another aim was evaluate the pharmacokinetics of sustained release formulation, which has not been established for dogs. Pharmacokinetic analysis of tramadol was evaluated using high performance liquid chromatography (HPLC) with tandem mass spectrometry for determination and quantification of tramadol in canine serum. The analyte and internal standard (IS) were extracted from serum using liquid-liquid method. Chromatographic separation was achieved on a C18 analytical column, kept at 30°C, under isocratic conditions of a mobile phase consisted by a mixture of acetonitrile and water contained 0,1% formic acid (80:20). Serum tramadol concentration was greater than the limit of quantification (LOQ) in 17 dogs. The dogs were divided into two groups, normal dogs (MDR1 +/+) and heterozygous (MDR1 +/-) according to the MDR1 genotype. The median values of maximum serum concentration (Cmax) were 63.13 ng/mL ± 33.35 for the normal group and 58.01 ng/mL ± 27.29 for the heterozygous group. Tmax (time to maximum serum concentration) was 4 h for both groups and t ½ (half-life) were 2,85h ± 1,61 e 2,81h ± 1,46 for normal and heterozygous dogs, respectively. The mean area-under-the-curve (AUC) values for the sustained release tramadol compounds for the normal and heterozygous group were 350,20 ±216,61 and 312,15 ± 155,43 ng.h/mL, respectively. The bioavailability was 22% and 23% for normal and heterozygous dogs respectively. There was no statistic difference between groups in all pharmacokinetics parameters. The findings suggest that tramadol is not a P-gp substrate. The amount of pharmacokinetics data of SR formulation of tramadol in dogs is sparse. Therefore, more studies of oral SR tramadol in dogs are needed to establish appropriate dose and frequency of administration in dogs.
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88

Dynamics and nonlinear thermo-acoustic stability analysis of premixed conical flames / Dynamique et analyse non-linéaire de stabilité thermo-acoustique de flammes coniques prémélangées

Cuquel, Alexis 11 June 2013 (has links)
Les instabilités thermo-acoustiques présentes dans les chambres de combustion sont générées par des interactions entre une flamme et l’acoustique du foyer. Ces oscillations auto-entretenues peuvent être observées dans de nombreux systèmes industriels tels que des chaudières domestiques, des fours industriels, des turbines à gaz ou des moteurs fusée. Bien que ce phénomène ait fait l’objet de nombreux travaux, il n’existe toujours pas de cadre d’étude assez général et robuste pour prédire le déclenchement de ces oscillations auto-entretenues et pour déterminer l’évolution des variables de l’écoulement à l’intérieur de la chambre de combustion. Ce travail s’appuie à la fois sur des modèles et des expériences. L’objectif est d’améliorer la description de la réponse de flammes coniques laminaires prémélangées à des perturbations de l’écoulement et les prédictions d’instabilités thermo-acoustiques dans des foyers alimentés par des flammes coniques. Dans la première partie du manuscrit, une revue des modèles décrivant la dynamique de flammes coniques est entreprise et un cadre général d’étude pour la modélisation de la Fonction de Transfert de Flamme (FTF) est présenté. Le dispositif expérimental ainsi que les diagnostics utilisés sont ensuite décrits. Ces systèmes sont utilisés pour mesurer la FTF de flammes coniques laminaires prémélangées soumises à des perturbations harmoniques de l’écoulement. Une nouvelle technique expérimentale est proposée pour contrôler les perturbations de l’écoulement à la sortie du brûleur. Elle est utilisée pour moduler l’écoulement avec un bruit blanc aléatoire et déterminer la FTF avec une résolution fréquentielle bien meilleure. Pour de faibles niveaux d’excitation, les résultats obtenus avec cette technique sont en accord avec ceux obtenus par la méthode classique utilisant des perturbations harmoniques. Les limites de cette technique sont décrites lorsque le niveau de perturbation augmente. Plusieurs expressions analytiques de la FTF de flammes coniques sont établies dans la seconde partie de cette thèse en introduisant progressivement plus de phénomènes physiques dans le modèle. Les modèles basés sur des perturbations convectées par l’écoulement sont étendus en tenant compte de la nature incompressible du champ de perturbation de vitesse. La prévision de la phase de la FTF de flamme conique est améliorée et présente un bon accord avec les mesures. Ensuite, une étude détaillée des interactions de la base de la flamme avec le bord du brûleur est conduite en tenant compte des pertes thermiques instationnaires de la flamme vers le brûleur. Ce mécanisme contrôle le mouvement de la base de la flamme et la dynamique de flamme à haute fréquence. Cette contribution à la FTF détermine le comportement haute fréquence de la FTF ainsi que l’évolution non-linéaire de la FTF lorsque le niveau de perturbation augmente. Enfin, une analyse de la dynamique des flammes coniques est entreprise pour des flammes placées dans des tubes de différents diamètres. Il est montré que les effets de confinement doivent être pris en compte lorsque les gaz brûlés ne peuvent se dilater complètement. Des différences importantes sont observées entre des FTF mesurées pour des tubes de confinement de diamètres différents. Un nouveau nombre sans dimension est établi pour prendre en compte ces effets. Ces différents modèles sont ensuite utilisés pour modéliser la réponse d’une collection de petites flammes coniques stabilisées sur une plaque perforée. Il est montré qu’une combinaison de ces modèles permet de capturer le comportement de ces flammes ainsi que l’évolution de la phase de la FTF couvrant le spectre fréquentiel pertinent pour la prédiction d’instabilités thermo-acoustiques. / Thermo-acoustic instabilities in combustion chambers are generated by the interactions between a flame and the combustor acoustics, leading to a resonant coupling. These self-sustained oscillations may be observed in many practical systems such as domestic boilers, industrial furnaces, gas turbines or rocket engines. Although this phenomenon has already been the topic of many investigations, there is yet no generalized robust framework to predict the onset of these self-sustained oscillations and to determine the evolution of the flow variables within the combustor during unstable operation. This work builds on previous models and experiments to improve the description of the response of laminar conical flames to flow perturbations and the prediction of thermoacoustic instability in burners operating with conical flames. In the first part of the manuscript, an extensive review of conical flame dynamics modeling is undertaken and a general framework for the modeling of their Flame Transfer Function (FTF) is presented. The experimental setup and the diagnostics used to characterize their response to flow disturbances are then described. They are used to measure the FTF when the flames are submitted to harmonic flow perturbations. A novel experimental technique is also proposed to control the flow perturbation level at the burner outlet. It enables to modulate the flow with random white noise perturbations and to measure the FTF with a better frequency resolution. Results with this alternative technique compare well with results from the classical method using harmonic signals for small disturbances. Limits of this technique are also highlighted when the perturbation level increases. Different analytical expressions for the FTF of conical flames are derived in the second part of the thesis by progressively introducing more physics into the models. Models based on convected flow disturbances are extended by taking into account the incompressible nature of the perturbed velocity field. It is shown that the prediction of the FTF phase lag of a conical flame is greatly improved and collapses well with measurements. Then, a thorough investigation of the flame base dynamics interacting with the anchoring device is conducted by considering unsteady heat loss from the flame to the burner. This mechanism is shown to drive the motion of the flame base and the flame dynamics at high frequencies. It is also shown that this contribution to the FTF rules the high frequency behavior of the FTF as well as the nonlinear evolution of the FTF when the perturbation level increases. Finally, an analysis is conducted on the dynamics of a single conical flame placed into cylindrical flame tubes featuring different diameters. It is shown that confinement effects need to be taken into account when the burnt gases cannot fully expand. Large differences are observed between FTF measured for different confinement tube diameters. A new dimensionless number is derived to take these effects into account and make all the FTF collapse on a single curve. These different models are then used to model the response of a collection of small conical flames stabilized on a perforated plate. It is shown that by sorting out the different contributing mechanisms to the FTF, the expressions proposed in this work may be combined to capture the main behavior and correct phase lag evolution of these flames in the frequency range of interest for thermo-acoustic instability prediction.
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89

Estudo sobre atividade auto sustentada em modelos de redes neurais corticais / Study on self-sustained activity in cortical neural network models

Diogo Porfirio de Castro Vieira 13 December 2013 (has links)
O entendimento de como a informação é representada e processada no cérebro e quais são os mecanismos necessários para que isto seja possível é um dos grandes desafios da neurociência. A atividade populacional das células corticais possui dinâmica emergente bastante complexa, apresentando padrões auto-sustentados mesmo na ausência de estímulos externos. Esses padrões de atividade podem representar estados internos de auto-organização da rede neural cortical. Porém, quais características da rede cortical seriam essenciais para o entendimento deste tipo de atividade? Podemos elencar duas características fundamentais: a organização topológica da rede e as características dinâmicas das unidades funcionais da rede (os neurônios). Neste trabalho estudamos a influência da topologia e da dinâmica dos neurônios sobre a atividade auto-sustentada de dois modelos corticais diferentes. O primeiro modelo possui arquitetura hierárquica e modular construída segundo uma estratégia top-down. As simulações com este modelo mostram que criação hierárquica de módulos favorece a atividade auto-sustentada em concordância com trabalhos anteriores de outros autores. Também observamos que diferentes classes funcionais de neurônios influenciam de maneiras distintas a atividade auto-sustentada da rede. O segundo modelo possui arquitetura em camadas com regras intra- e inter-laminares específicas baseadas em dados anatômicos do córtex visual primário de gatos. As simulações com este modelo mostram um importante papel das condutâncias sinápticas excitatórias e inibitórias sobre o início da atividade auto-sustentada na rede, especialmente sobre a largura (intervalo de valores da condutância excitatória) da zona de transição entre as regiões com e sem atividade auto-sustentada no diagrama de condutâncias sinápticas. Conclui-se que a topologia da rede cortical e sua composição em termos de combinações de neurônios de diferentes tipos têm importante papel sobre a existência e as propriedades da atividade auto-sustentada na rede. / To understand how information is represented and processed in the brain and the necessary mechanisms for this is one of the major challenges in neuroscience. The population activity of cortical cells has complex and emergent dynamics, showing self-sustained activity patterns even in the absence of external stimuli. These activity patterns may represent internal self-organizing states of the cortical network. Which characteristics that make up the cortical network would be essential to understand this type of activity? We can list two basic characteristics: the topological organization of the network and the dynamic characteristics of its functional units (the neurons). In this work we studied the influence of topology and neuronal dynamics on self-sustained activity in two different cortical network models. The first model has hierarchical and modular architecture constructed according to a top-down strategy. Simulations with this model show that the hierarchical creation of modules favors self-sustained activity in agreement with results from other authors. We also observed that different functional neuronal classes influence in distict ways the self-sustained activity. The second model has a layered architecture with specific intra- and inter-laminar rules based on anatomical evidence from the primary visual cortex of cats. Simulations with this model show an important role of excitatory and inhibitory synaptic conductances on the beginning of self-sustained network activity, specially on the width of the border (range of excitatory conductance values) between regions with and without self-sustained activity in the excitatory-inhibitory synaptic conductances diagram. We conclude that network topology and its composition in terms of combinations of neurons with different dynamics have an important role on the existence and properties of self-sustained activity in the network.
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90

Estudo dendrológico e anatômico do lenho das árvores do Parque da Escola Superior de Agricultura \"Luiz de Queiroz\", Universidade de São Paulo: subsídios para a sua conservação / Dendrological and anatomical of wood study of the trees of the \"Luiz de Queiroz\" School of Agriculture, University of São Paulo: subsidies for conservation

Luiz Santini Junior 03 July 2018 (has links)
O termo \"área verde\" é compreendido como espaços urbanos que têm em comum a acessibilidade, a relação da saúde, recreação e que proporcionam interação das atividades humanas com o meio ambiente, atuando no equilíbrio climático e na qualidade de vida nas cidades como filtro ou barreira natural do vento, som e particulados do ar, melhorando a qualidade do clima, do solo, da água, fauna e flora, etc. Neste contexto destaca-se o Parque Philippe Westin Cabral de Vasconcelos, conhecido como Parque da ESALQ, localizado no Campus da Universidade de São Paulo, em Piracicaba/SP. Com aproximadamente 15h é o segundo maior parque em extensão e o mais frequentado dentre os cinco parques existentes no município, inaugurado em 1907 e passou a representar um patrimônio digno de preservação, pelo aspecto histórico e pelo valor científico, didático, ecológico e cultural, sendo tombado em 2006. Seu histórico é marcado por uma dinâmica de reformas e intervenções para melhoria e modernização da área, além do manejo inadequado que estão comprometendo a manutenção do projeto paisagístico original. Assim, no intuito de subsidiar um Plano de Manejo Sustentado para o Parque da ESALQ, o presente estudo foi dividido em três capítulos: o primeiro faz um levantamento florístico das 100 principais espécies arbóreas que compõem o Parque da ESALQ, para elaboração do \"Guia Ilustrado das Árvores da ESALQ\", com a caracterização dendrológica e anatômica do lenho das espécies. Foi identificada predominância da família Leguminosae, seguida das famílias Malvaceae e Bignoniaceae. Sobre a importância, as mais abundantes foram as espécies produtoras de madeira de qualidade (46%), seguindo-se as de importância paisagística e ornamental (28%), e produção de frutos e aplicação medicinal (12-14%) e ainda 10 espécies que se encontram sob algum grau de ameaça. No capítulo 2, foram identificados alguns dos principais problemas que comprometem a conservação do Parque da ESALQ, por meio de cinco estudos de caso. Os resultados apontam para sucessivas práticas de podas irregulares nos ramos das árvores que estão levando as espécies à senescência, pela exposição do tecido lenhoso e consequente estabelecimento de organismos xilófagos. A ocorrência de espécies exóticas invasoras vegetais infestando diversas áreas do parque e competindo por recursos com as árvores do local foi outro grave problema identificado. Também se constatou a presença de animais domésticos errantes (gatos e cães) que estão relacionados com a predação de algumas espécies nativas do local (aves e mamíferos), além de árvores caídas e tocos remanescentes de antigas supressões que representam via de acesso e estabelecimento de fungos e cupins que podem infectar árvores sadias. A abertura de valetas para manutenção e substituição de encanamentos levou à destruição de partes de algumas raízes de pau Brasil (Paubrasilia echinata) e Mirindiba rosa (Lafoensia glyptocarpa) afetando no desenvolvimento natural das árvores. Todos os fatores apontados colocam em risco a conservação do parque e precisam ser pautados nas discussões para criação do Plano de Manejo Sustentado do Parque da ESALQ. Por fim, o capítulo 3 versa sobre a potencialidade na utilização de três métodos não destrutivos para análise da biodeterioração do lenho causada por fungos em cinco espécies arbóreas do Parque da ESALQ. A preparação de lâminas histológicas permitiu analisar a extensão das injúrias causadas no lenho, com diferentes níveis de destruição da estrutura anatômica da madeira. Já a aplicação da microdensitometria de raios x e de fluorescência de raios X, para elaboração dos perfis físicos e químicos, revelaram alterações significativas nas amostras entre as regiões sadias e afetadas do lenho. Sob o ponto de vista físico, tais alterações estão relacionadas à perda de densidade nas regiões de lenho doente e aumento nas regiões de compartimentalização (isolamento físico-químico). Por sua vez, o perfil químico aponta para ocorrência de alguns elementos principais que podem estar relacionados com a resposta fisiológica da planta ao ataque de patógenos. Dessa forma, o presente estudo permitiu identificar as principais espécies arbóreas do Parque da ESALQ, além do apontamento dos principais problemas que comprometem sua conservação, que pode servir como documento de apoio à elaboração de um plano de manejo sustentado que contribua para conservação desta histórica área verde do estado de São Paulo. / The term \"green area\" is understood as urban spaces that have in common the accessibility, the relationship of health, recreation and that provide interaction of human activities with the environment, acting on climate balance and quality of life in cities as filter or natural wind barrier, sound and particulates of the air, improving the quality of climate, soil, water, fauna and flora, etc. In this context stands the Philippe Westin Cabral de Vasconcelos Park, known as the ESALQ\'s Park, located on the University of São Paulo, Campus Piracicaba/SP. With approximately 15 ha, it is the second largest park in extension and the most frequented of the five existing parks in the municipality, inaugurated in 1907 and started to represent a patrimony worthy of preservation, by the historical aspect and by the scientific, didactic, ecological and cultural value, being in 2006. Its history is marked by a dynamic of reforms and interventions to improve and modernize the area, as well as inadequate management that are compromising the maintenance of the original landscape project. Thus, in order to subsidize a Sustainable Management Plan for the ESALQ\'s Park, the present study was divided into three chapters: the first one makes a floristic survey of the 100 main tree species that compose the ESALQ\'s Park, for the elaboration of the \"Illustrated Guide of the ESALQ\'s Trees \", with the dendrological and anatomical characterization of the wood of the species. It was identified predominance of the family Leguminosae, followed by the families Malvaceae and Bignoniaceae. Regarding importance, the most abundant were quality wood species (46%), followed by those of landscape and ornamental importance (28%), fruit production and medicinal application (12-14%) and 10 species that are under some degree of threat. In chapter 2, we identified some of the main problems that compromise the conservation of the ESALQ\'s Park, through five case studies. The results point to successive practices of irregular pruning in the branches of the trees that are leading the species to senescence, by the exposure of the woody tissue and the consequent establishment of xylophagous organisms. The occurrence of exotic invasive plant species infesting several areas of the park and competing for resources with the local trees was another serious problem identified. There were also the presence of wandering domestic animals (cats and dogs) that are related to the predation of some native species of the place (birds and mammals), as well as fallen trees and stumps remaining of old suppressions that represent way of access and establishment of fungi and termites that can infect healthy trees. The opening of ditches for maintenance and replacement of pipelines led to the destruction of parts of some Brazil wood roots (Paubrasilia echinata) and Mirindiba rosa (Lafoensia glyptocarpa), affecting the natural development of the trees. All the factors pointed out pose a risk to the conservation of the park and must be based on the discussions to create the Sustainable Management Plan of the ESALQ\'s Park. Finally, Chapter 3 deals with the potential use of three nondestructive methods to analyze the biodeterioration of the wood caused by fungi in five tree species of the ESALQ\'s Park. The preparation of histological slides allowed to analyze the extent of the injuries caused in the wood, with different levels of destruction of the anatomical structure of the wood. On the other hand, the application of x-ray microdensitometry and X-ray fluorescence, for the elaboration of physical and chemical profiles, revealed significant alterations in the samples between the healthy and affected regions of the wood. From the physical point of view, these alterations are related to the loss of density in the regions of diseased wood and increase in the regions of compartmentalization (physical-chemical isolation). In turn, the chemical profile points to the occurrence of some main elements that may be related to the physiological response of the plant to the attack of pathogens. In this way, the present study allowed to identify the main tree species of the ESALQ\'s Park, as well as the main problems that compromise its conservation, which can serve as a document to support the elaboration of a sustainable management plan that contributes to the conservation of this historic area of the state of São Paulo.
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