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1
Zimmermann, Estevan Sonego. „Modelagem farmacocinética populacional na avaliação do papel da glicoproteína-P na penetração tecidual de fluoroquinolonas“. reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/163764.
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Objetivos: O objetivo deste trabalho foi desenvolver modelo farmacocinético (popPK) populacional para descrever simultaneamente as concentrações das fluoroquinolonas (levofloxacino – LEV e ciprofloxacino – CIP) no plasma, pulmão e próstata na presença e ausência do inibidor da P-gp tariquidar (TAR) visando determinar a contribuição desse transportador de efluxo na distribuição tecidual desses antimicrobianos. Método: Para alcançar este objetivo as seguintes etapas foram realizadas: i) foi validado o método analítico de HPLC-fluorescência para quantificação de CIP em amostras de plasma e microdialisado; ii) foram estabelecidas as condições para microdiálise para o CIP e as taxas de recuperação in vitro, por diálise e retrodiálise, e em tecido pulmonar e prostático in vivo por retrodiálise; iii) foi avaliada a farmacocinética do LEV após administração a ratos Wistar via i.v. bolus e por nebulização intratraqueal na dose de 7mg/kg na ausência e após administração prévia de TAR (15 mg/Kg i.v.); iv) foi desenvolvido um modelo popPK para prever as concentrações do LEV simultaneamente no plasma, pulmão e próstata após administração intravenosa e intratraqueal na presença e ausência do TAR; v) foi desenvolvido o modelo popPK para descrever as concentrações de CIP simultaneamente no plasma, pulmão e próstata após administração a ratos Wistar da dose de 7 mg/kg i.v. bolus na presença e ausência de TAR (15 mg/kg i.v.); vi) Para ambos os fármacos os dados foram avaliados por análise não-compartimental e modelados por modelo de quatro compartimentos modificado, com ajuda do software NONMEN®. Resultados e Conclusões. i) Método analítico foi desenvolvido e validado com sucesso para quantificação de CIP em HPLC/fluorescência mostrando-se linear na faixa de 10–2000 ng/mL em plasma e 5–1000 ng/mL em microdialisado com coeficientes de determinação (r2) superiores a 0,99. Os valores obtidos de erro padrão relativo para ensaios de precisão intra e inter-dia foram entre 8,8 e 6,0 %, para microdialisado entre 11,1 e 7,4 % para plasma, respectivamente. Os valores de exatidão foram 86,1% entre 114.3% para microdialisado e 85,6% entre 108,2% para plasma; ii) A avaliação do CIP por microdiálise mostrou recuperação concentração independente (0,25 - 1,5 μg/mL). Além disso, não houve diferença entre as recuperações obtidas por diálise e retrodiálise para o mesmo fluxo. No fluxo selecionado para os experimentos (1,5 μL/min) as recuperações médias por diálise e retrodiálise foram 23,0 ± 2,8% e 22,8 ± 1,6 %, respectivamente. A recuperação relativa das sondas in vivo foi de 11,3 ± 1,9 e 13,1 ± 2,7 % para pulmão e próstata, respectivamente; iii) A análise dos perfis plasmáticos e teciduais LEV após dose intravenosa do grupo controle (sem TAR) mostrou boa penetração tecidual na próstata (ƒT = 0,68) e no pulmão (ƒT = 0,69). Para a mesma via de administração, o grupo TAR mostrou uma penetração praticamente inalterada para o pulmão (ƒT = 0,81) e um aumento de mais de 2 vezes na penetração prostática (ƒT= 1,64). Na dose intratraqueal houve um aumento significativo na biodisponibilidade para o grupo TAR (F = 0,86) em relação ao controle (F = 0,4). Nessa via de administração foi detectado um aumento significativo na exposição (ASC) do pulmão ao LEV no grupo TAR demonstrando que o transporte por efluxo no pulmão é mais relevante quando o fármaco é administrado pela via intratraqueal; iv) Para o LEV, o modelo popPK de quatro compartimentos foi capaz de descrever simultaneamente os dados no plasma, pulmão e próstata na presença e ausência do TAR. Além disso, o modelo para administração intravenosa foi estendido e adaptado para administração intratraqueal. Foi possível analisar o impacto do transporte por efluxo sobre a penetração tecidual do LEV por diferentes vias de administração utilizando o modelo popPK; v) A avaliação do perfil farmacocinético plasmático do CIP após administração intravenosa, na presença e ausência de TAR, demonstrou diferença significativa entre todos os parâmetros calculados por análise não-compartimental, exceto para a constante de velocidade de eliminação (= 0,05). Em relação à penetração tecidual do CIP na próstata e pulmão, não houve alteração significativa nos parâmetros de eliminação e exposição tecidual do fármaco na presença do inibidor de efluxo TAR ( = 0,05), demonstrando que o transporte por efluxo possui papel minoritário no processo de distribuição do fármaco para os tecidos estudados. O modelo popPK de quatro compartimentos foi capaz de descrever as concentrações plasmáticas totais, livres no pulmão e próstata em presença e ausência de TAR, simultaneamente; vi) O modelo popPK desenvolvido permitiu o estudo mais profundo do processo de distribuição do LEV e do CIP no pulmão e próstata.Objectives: The aim of this study was to develop a population pharmacokinetic model (popPK) able to simultaneously describe fluoroquinolones (levofloxacin – LEV and ciprofloxacin – CIP) concentrations in plasma, lung and prostate in the presence and absence of the inhibitor of P-gp tariquidar (TAR) to determine the contribution of this efflux transporter on the tissue distribution of these antimicrobials. Methods: To achieve this goal the following steps were taken: i) An analytical method by HPLC-fluorescence was developed and validated for CIP analysis in plasma and microdialysate samples; ii) microdialysis conditions were established for CIP including determination of in vitro relative recovery by dialysis and retrodialysis. The relative recovery was also determined in vivo, in lung and prostate, by retrodialysis; iii) LEV pharmacokinetics was evaluated after intravenous (i.v.) bolus and intratracheal (i.t.) administration of 7 mg/kg dose alone and following TAR administration (15 mg/kg i.v.) to Wistar rats; iv) a popPK model was developed to describe and predict LEV concentrations in plasma, lung and prostate following i.v. and i.t. dosing with and without TAR co-administration; v) the popPK model developed was used to describe CIP concentrations in plasma, lung and prostate after i.v. bolus administration of 7 mg/kg in presence and absence of TAR; vi) For both drugs non-compartmental analysis was performed besides data modeling by four compartment model using NONMEN®. Results and Conclusions i) The analytical method was developed and successfully validated for quantification of CIP by HPLC/fluorescence. The method was linear in the range of 10-2000 ng/mL in plasma and 5-1000 ng/mL in tissues microdialysate samples with coefficients of determination (r2) higher than 0.99. The relative standard error (RSD) obtained for intra and inter-day precision were lower than 8.8% and 6.0% for microdialysate and lower than 11.1 and 7.4% for plasma, respectively. The accuracy was 86.1% to 114.3% for microdialysate and 85.6 to 108.2 % for plasma samples; ii) the evaluation of CIP microdialysis probes relative recovery in vitro showed that the recovery was concentration independent (0.25 to 1.5 μg/mL). In addition, there was no statistical difference between the recoveries determined by dialysis and retrodialysis at the same flow rate. Using the selected flow rate (1.5 μL/min) the recoveries by dialysis and retrodialysis were 23.0 ± 2.8% and 22.8 ± 1.6%, respectively. CIP relative recoveries in vivo by retrodialysis were 11.3 ± 1.9 and 13.1 ± 2.7% for lung and prostate, respectively; iii) the analysis of LEV plasma and tissues concentration-time profiles after i.v. dosing showed a good tissue penetration of LEV in the prostate (ƒT = 0.68) and lung (ƒT = 0.69). For the same route of administration, TAR group showed virtually the same penetration into lung (ƒT = 0.81) and an increase of over 2 fold in drug levels in prostate (ƒT = 1.64). For the i.t. dose, there was a significant increase on LEV bioavailability for TAR group (F = 0.86) compared to control (F = 0.4). Furthermore, a significant increase was detected on lung exposure to LEV for TAR group indicating that efflux transport in the lung is more relevant when the drug is administered by the i.t. route; iv) For LEV, a four compartment model was able to describe the data simultaneously in plasma, lung and prostate in the presence and absence of TAR. Moreover, the intravenous model was extended to adapt the intratracheal dosing route. The popPK model allowed to analyze the impact of efflux transport on tissue LEV penetration of different routes of administration; v) the evaluation of plasma CIP profiles after i.v. dosing with and without TAR showed a significant difference in all parameters determined by non-compartmental analysis in the TAR group, except the elimination rate constant (α = 0.05). The CIP tissue penetration in prostate and lung, no significant difference was observed in tissues exposure and elimination rate when TAR was present demonstrating that efflux transporter play a minor role on CIP distribution to tissues investigated (α = 0.05). The popPK model with four compartments was able to describe CIP concentrations in plasma, lung and prostate in the presence and absence of TAR, simultaneously; vi) the popPK model developed allowed a more detailed investigation of LEV and CIP distribution process in lung and prostate.
2
Bernardi, Priscila Martini. „Avaliação por microdiálise da penetração pulmonar da tobramicina em modelo de pneumonia por microrganismo formador de biofilme“. reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/149491.
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Objetivo: Avaliar a influência da infecção por Pseudomonas aeruginosa formadora de biofilme na penetração pulmonar da tobramicina através da modelagem populacional dos dados de plasma e microdialisado em animais sadios e infectados. Metodologia: A pneumonia foi desenvolvida através de inoculação de P. aeruginosa (cepa PA14) pela via intratraqueal (109 UFC/mL) a ratos Wistar. Sete dias após a inoculação os animais infectados (n = 5) receberam tobramicina 10 mg/kg i.v. bolus. Animais saudáveis (n = 6) foram utilizados como controle. As concentrações livres pulmonares foram coletadas por microdiálise (sonda CMA/20). As sondas de microdiálise foram calibradas in vitro através de diálise e retrodiálise e in vivo utilizando retrodiálise. A ligação da tobramicina às proteínas plasmáticas foi determinada por microdiálise. As concentrações do fármaco nas amostras foram determinadas por cromatografia líquida em tandem com espectrometria de massas (CLAE-EM/EM) utilizando metodologia validada. Os parâmetros farmacocinéticos foram determinados por abordagem não-compartimental (Phoenix®) e modelagem populacional (popPK) (Monolix®). Resultados e Discussão: A recuperação relativa (RR) das sondas foi independente da concentração de tobramicina e inversamente proporcional ao fluxo de perfusão. A RR determinada in vivo foi de 27,64 % ± 7,70 para animais sadios e 24,47 % ± 1,66 para animais infectados. A ligação às proteínas plasmáticas foi de 11,3 ± 1,9%. A infecção com formação de biofilme não alterou a farmacocinética plasmática da tobramicina, entretanto reduziu em cerca de 70% a penetração pulmonar do fármaco. As concentrações plasmáticas e teciduais foram simultaneamente descritas por um modelo farmacocinético populacional de dois compartimentos, tanto em animais sadios como infectados. A infecção, utilizada como covariável categórica, permitiu descrever as alterações no volume do compartimento periférico e na constante de eliminação do compartimento central devido à infecção. Conclusões: As concentrações plasmáticas da tobramicina, utilizadas para ajuste posológico, superestimam as concentrações ativas no pulmão infectado. O modelo popPK descrito permite a previsão das concentrações livres pulmonares da tobramicina em pulmão infectado, podendo auxiliar na otimização da terapia de pneumonias com P. aeruginosa formadora de biofilme.Objective: To evaluate the influence of biofilm-forming Pseudomonas aeruginosa infection on tobramycin lung penetration by population pharmacokinetic modeling of plasma and microdialysate data in healthy and infected rats. Methodology: The infection was developed by intratracheal inoculation (109 CFU/mL) of P. aeruginosa (PA14 strain) to Wistar rats. In order to determine plasma and tissue concentrations, seven days after the inoculation the infected animals (n = 5) received tobramycin 10 mg/kg i.v. bolus dose via femoral vein. A healthy group (n = 6) was used as control. Free lung concentrations were determined in microdialysate samples obtained using CMA/20 probes. Microdialysis probes were calibrated in vitro by dialysis and retrodialysis and in vivo by retrodialysis. Tobramycin plasma protein binding was determined by microdialysis. Plasma and tissue concentrations were quantified by a developed and validated liquid chromatography in tandem with mass spectrometry (LC-MS/MS) method. Compartmental and non-compartmental analyses were carried out by Monolix™ and Phoenix™ software, respectively. Results and Discussion: Microdialysis probes relative recovery was independent of the tobramycin concentration and is inversely proportional to the perfusion flow rate investigated. The in vivo probe recovery was 27.64 % ± 7.70 (healthy rats) and 24.47 % ± 1.66 (infected rats). The plasma protein binding was 11.3 ± 1.9%. The biofilm-forming lung infection did not alter tobramycin plasma pharmacokinetics, however, reduced lung penetration in about 70%. The plasma and tissue concentrations-time profiles were simultaneously described by a two compartment popPK model in healthy and infected animals. The infection process, used as categorical covariate allowed describing the changes observed in the volume of the peripheral compartment and in constant rate of elimination from the central compartment. Conclusions: Tobramycin plasma concentrations, used for dosing adjustments, overestimate active concentrations in infected lung. The described popPK model allows predicting free tobramycin lung concentrations in infected lung and could be useful to optimize the treatment of pneumonia caused by biofilm-forming P. aeruginosa with this drug.
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Torres, Bruna Gaelzer Silva. „Modelagem farmacocinética/farmacodinâmica (PK/PD) para caracterização do efeito do ciprofloxacino em infecções com biofilmes de Pseudomonas aeruginosa“. reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/159488.
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Biofilmes são comunidades bacterianas complexas encapsuladas em matrizes poliméricas autoproduzidas e podem se desenvolver em superfícies inertes ou tecidos vivos. A formação do biofilme é um importante fator de virulência, pois permite à bactéria resistir às respostas do hospedeiro e à terapia antimicrobiana. Devido a essa elevada resistência aos antimicrobianos, é difícil estabelecer uma estratégia eficaz para o tratamento de infecções com formação de biofilmes, levando a falhas na erradicação das mesmas. Nesse contexto, o objetivo do presente estudo é desenvolver um modelo farmacocinético/farmacodinâmico (PK/PD) para descrever o efeito do ciprofloxacino (CIP) na presença de biofilmes de Pseudomonas aeruginosa (ATCC 27853), visto que a modelagem PK/PD de antimicrobianos é uma ferramenta útil na escolha de regimes posológicos que atinjam o efeito bactericida máximo, minimizando o desenvolvimento de resistência. Para atingir esse objetivo, inicialmente um método analítico por CLAE/fluorescência foi desenvolvido para quantificar o CIP em amostras de plasma e microdialisado. O método desenvolvido foi simples, rápido e com sensibilidade adequada para corretamente caracterizar a farmacocinética plasmática e pulmonar do CIP. Posteriormente, um modelo animal de infecção pulmonar crônica foi adaptado da literatura e padronizado, permitindo a investigação da distribuição pulmonar do CIP em ratos Wistar sadios e infectados. Para tal, bactérias foram imobilizadas em beads de alginato a fim de manter a infecção por até 14 dias com cargas bacterianas superiores à 108 UFC/pulmão. Estudo de microdiálise foi então conduzido para avaliar as concentrações livres de CIP após administração intravenosa de 20 mg/kg. A análise não-compartimental (NCA) e a modelagem farmacocinética populacional (PopPK) dos dados foram realizadas nos softwares Phoenix® e NONMEM®, respectivamente. Diferenças significativas foram observadas no clearance plasmático (1,59 ± 0,41 L/h/kg e 0,89 ± 0,44 L/h/kg) e na constante de eliminação (0,23 ± 0,04 h-1 e 0,14 ± 0,08 h-1) para ratos sadios e infectados, resultando em uma exposição plasmática maior nos animais infectados (ASC0-∞ = 27,3 ± 12,1 μg·h/mL) quando comparados com os animais sadios (ASC0-∞ = 13,3 ± 3,5 μg·h/mL) ( = 0,05). Apesar da maior exposição plasmática, quando comparados com os animais saudáveis (fT = 1,69), animais infectados apresentaram uma penetração pulmonar quatro vezes menor (fT = 0,44). Diferenças na constante de eliminação pulmonar não foram observadas. Dados plasmáticos e pulmonares foram simultaneamente descritos por modelo PopPK constituído de compartimentos venoso e arterial, dois compartimentos representativos de duas regiões pulmonares distintas e dois compartimentos periféricos, representando outros tecidos que não os pulmões. Um clearance pulmonar foi adicionado ao modelo apenas para os dados de microdiálise dos animais infectados (CLlung = 0,643 L/h/kg) afim de explicar a exposição tecidual diminuída. O modelo desenvolvido descreveu, com sucesso, os dados plasmáticos e teciduais de animais sadios e infectados, permitindo a correta caracterização das alterações observadas na disposição plasmática e pulmonar do CIP decorrentes da infecção com biofilme. Para os estudos de farmacodinâmica, o efeito bactericida do CIP frente a biofilmes e células planctônicas de P. aeruginosa foi simultaneamente avaliado através do uso de curvas de morte bacteriana. Para a construção destas curvas, biofilmes de P. aeruginosa foram formados na superfície de blocos de acrílico e sua formação foi confirmada pelo ensaio cristal violeta e por microscopia eletrônica de varredura. Os blocos foram expostos a concentrações constantes de CIP (de 0,0625 a 10 μg/mL) e, em tempos pré-determinados, células planctônicas e de biofilmes eram amostradas para quantificação. Um modelo semi-mecanístico que incorpora um modelo Emax sigmoidal foi utilizado para descrever o efeito do CIP frente a ambos estilos de vida bacteriano. Uma subpopulação pré-existente com menor suscetibilidade ao CIP foi incluída no modelo e o efeito do CIP nesta subpopulação também foi descrito pelo modelo Emax sigmoidal. A comparação dos parâmetros estimados pelo modelo demonstrou que o efeito in vitro do CIP é maior para as células planctônicas (EC50 = 0,259 mg/L e 0,123 mg/L e Emax = 2,25 h-1 e 5,59 h-1 para biofilmes e planctônicas, respectivamente). A potência estimada do CIP para a subpopulação resistente foi muito menor para ambos estilos de vida bacteriano (EC50 = 2,71 mg/L e 1,15 mg/L para biofilmes e planctônicas, respectivamente). Os modelos desenvolvidos podem ser utilizados para a simulação de cenários não testados e servir como uma ferramenta para guiar a escolha dos regimes posológicos adequados, contribuindo para o sucesso terapêutico no tratamento de infecções associadas à biofilmes.Biofilms are complex bacterial communities enclosed in self-produced polymeric matrices that can develop in inert surfaces or living tissues. Biofilm formation is an important virulence factor that allows bacteria to resist host responses and antibacterial agents. Due to this high resistance to antibiotics, it is difficult to establish an efficacious strategy for treatment of infections with biofilm formation leading to failure in infection eradication. In this context, the goal of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the antimicrobial effect of ciprofloxacin (CIP) in the presence of biofilms of Pseudomonas aeruginosa (ATCC 27853), since PK/PD modeling for antibacterial agents can be a useful tool to choose dosing regimens and to achieve the maximum bactericidal effect, minimizing the development of resistance. To reach this goal, firstly an analytical method based on HPLC/fluorescence was developed in order to quantify CIP in plasma and lung microdialysate. The developed method was simple, fast and with enough sensibility to proper characterize CIP plasma and lung pharmacokinetics. Secondly, an animal model of chronic lung infection was adapted from literature and standardized, allowing the analysis of CIP lung distribution in infected and healthy Wistar rats. Bacteria were immobilized in alginate beads prior to inoculation to Wistar rats in order to sustain the pneumonia for 14 days, maintaining a bacterial load superior to 108 CFU/lung. A microdialysis study was then conducted to evaluate free CIP concentrations after an intravenous administration of 20 mg/kg. Non-compartimental analysis (NCA) and populational PK modeling (PopPK) of the data were performed in Phoenix® and NONMEM®, respectively. Statistical differences were observed in the plasma clearance (1.59 ± 0.41 L/h/kg and 0.89 ± 0.44 L/h/kg) and elimination rate constant (0.23 ± 0.04 h-1and 0.14 ± 0.08 h-1) for healthy and infected rats, respectively, resulting in a significantly higher CIP plasma exposure in infected rats (AUC0-∞ = 27.3 ± 12.1 μg·h/mL) compare to healthy animals (AUC0-∞ = 13.3 ± 3.5 μg·h/mL) ( = 0.05). Besides the plasma exposure, a four times lower pulmonary penetration was observed in infected rat’s lungs (fT = 0.44) in comparison to healthy animals (fT = 1.69), with no significant differences in the lung elimination rate constant. Plasma and lung data were simultaneously fitted using a PopPK model consisting of an arterial and a venous compartment, two compartments representing different regions of the lungs and two peripheral distribution compartments, representing tissues other than lungs. A lung clearance was added to the model for infected animals (CLlung = 0.643 L/h/kg) to explain the lower tissue exposure. The model successfully described the plasma and microdialysis data from both, healthy and infected rats and allowed to correctly describe the changes in CIP plasma and lung disposition in biofilm infections. For the pharmacodynamic studies, CIP bactericidal effect against Pseudomonas aeruginosa biofilms and planktonic shedding cells were simultaneously evaluated using the time-kill curves approach. For the time-kill curves construction, P. aeruginosa biofilms were formed in acrylic blocks, which was confirmed by the crystal violet assay and scanning electron microscopy. The blocks were placed in flasks containing Mueller-Hinton growth medium and exposed to constant CIP concentrations (ranging from 0.0625 to 10 μg/mL). At pre-determined time points, biofilm and planktonic cells were sampled for bacterial counting. A mechanism-based model which incorporates a sigmoidal Emax model was used to describe the CIP effect against P.aeruginosa in both llifestyles, biofilm and planktonic. The presence of a pre-existing resistant subpopulation was included in the model and also modeled with a sigmoidal Emax model to describe CIP effect in this subpopulation. Comparison of the parameter estimates showed that the in vitro effect of CIP is higher for planktonic cells (EC50 = 0.259 mg/L and 0.123 mg/L and Emax = 2.25 h-1 and 5.59 h-1 for biofilm and planktonic cells, respectively). CIP potency was much lower for the resistant subpopulation, for both bacteria lifestyles (EC50 = 2.71 mg/L and 1.15 mg/L for biofilm and planktonic, respectively). The developed models can be used to simulate untested scenarios and serve as a tool to guide dosing regimen selection, contributing for the therapeutic success of treatments of biofilm-associated infections.
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Bicchierai, Marco. „Ai confini della Repubblica di Firenze : Poppi dalla Signoria dei Conti Guidi al vicariato del Casentino /“. Firenze : Leo S. Olschki, 2005. http://catalogue.bnf.fr/ark:/12148/cb40071465v.
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Dediu, Igorevna. „Tall Poppy Syndrome and its effect on work performance“. Thesis, University of Canterbury. Psychology, 2015. http://hdl.handle.net/10092/10261.
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The aim of this study was to find out whether employees would perform worse if they perceived their work colleagues to have negative attitudes towards tall poppies (colleagues favoured the fall of tall poppies rather than rewarding tall poppies), thus displaying typical tall poppy syndrome perceptions. Performance measures were: decision-making vigilance, decision-making dependence, decision-making avoidance, problem solving, creativity, service quality, and the personality construct need for affiliation. Control variables were age, tenure and need for achievement. The design of the study was cross-sectional, online surveys were used to collect the data. The link to the survey was distributed using LinkedIn groups and Facebook advertising, yielding a sample of 229 participants. The data was analysed using regression; the results confirmed 3 of the 7 hypotheses. The results indicated that employees working in an environment that favoured the fall of tall poppies, showed lower decision-making dependability and higher decision-making avoidance. Internal service quality was partially confirmed, it was negatively associated with participants working in an environment that favoured the fall of tall poppies, rather than reward; Theories about the contribution New Zealand’s history has made to the development of tall poppy syndrome are considered. Practical implications of the results are discussed. Directions for future studies in industrial and organizational psychology on the effects of tall poppy syndrome on work performance are discussed.
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Giovannetti, Alessandra. „Francesco Morandini detto il Poppi /“. Firenze : EDIFIR, 1995. http://catalogue.bnf.fr/ark:/12148/cb37521462h.
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Leding, Albin. „Recommendation for first pharmacokinetic in vivo experiment design with a pharmacometric informed approach“. Thesis, Uppsala universitet, Institutionen för farmaci, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447311.
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Tuberculosis, the leading cause of death by a single infection disease caused by bacteria, requires long treatments and the bacteria are prone to develop drug resistance. Therefore, new efficient treatment regiments needs developing, which requires new tools for drug development. A major reason for discontinuance of a drug under development is undesired pharmacokinetic properties. Therefore, it is important to have early information of this, preferably the first time the drug is tested in animals. The first in vivo pharmacokinetic experiment is often done in mice and the only information present at this stage are often in vitro values and physicochemical properties. Physiological-based pharmacokinetic modelling can be used to extrapolate from in vitro to in vivo values. From this, the first in vivo pharmacokinetic experiment can be designed, often with the goal of reducing the amount of mice. This goal is one of the three R.s and it is called Reduction. To explore the Reduction of an experiment population pharmacokinetic modelling can be utilized via exploration of the imprecision, bias and probability of an informative experiment to evaluate if a design meets the goal of Reduction. In this report a recommendation of the first in vivo pharmacokinetic experiment is presented. This is based on in vitro values and physicochemical properties that are common in anti-tuberculosis drugs. If the probability of an informative experiment is critical, a terminal sampling of 40 mice is recommended. If imprecision and bias are necessary, zipper sampling of 10 mice is recommended.
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Leding, Albin. „Optimized design recommendation for first pharmacokinetic in vivo experiments for new tuberculosis drugs using pharmacometrics modelling and simulation“. Thesis, Uppsala universitet, Institutionen för farmaci, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447311.
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Tuberculosis, the leading cause of death by a single infection disease caused by bacteria, requires long treatments and the bacteria are prone to develop drug resistance. Therefore, new efficient treatment regiments needs developing, which requires new tools for drug development. A major reason for discontinuance of a drug under development is undesired pharmacokinetic properties. Therefore, it is important to have early information of this, preferably the first time the drug is tested in animals. The first in vivo pharmacokinetic experiment is often done in mice and the only information present at this stage are often in vitro values and physicochemical properties. Physiological-based pharmacokinetic modelling can be used to extrapolate from in vitro to in vivo values. From this, the first in vivo pharmacokinetic experiment can be designed, often with the goal of reducing the amount of mice. This goal is one of the three R.s and it is called Reduction. To explore the Reduction of an experiment population pharmacokinetic modelling can be utilized via exploration of the imprecision, bias and probability of an informative experiment to evaluate if a design meets the goal of Reduction. In this report a recommendation of the first in vivo pharmacokinetic experiment is presented. This is based on in vitro values and physicochemical properties that are common in anti-tuberculosis drugs. If the probability of an informative experiment is critical, a terminal sampling of 40 mice is recommended. If imprecision and bias are necessary, zipper sampling of 10 mice is recommended.
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Day, Keith B. „Papaver somniferum and P. bracteatum : tissue culture and morphinan alkaloid production“. Thesis, University of Leicester, 1987. http://hdl.handle.net/2381/35449.
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Papaver somniferum plants accumulate the secondary products codeine and morphine. P. bracteatum accumulates their precursor, thebaine. The aims of the project were to use tissue cultures for the production of these alkaloids and for the biotransformation of thebaine to codeine and morphine. Methods were evaluated for the extraction, separation and quantification of mg or mug amounts of morphinan alkaloids from plant material. TLC, IIPLC and RIA were useful. Poppy cells fron a range of seed sources and explants were grown in static and suspension culture. Manipulations were made in atterpts to induce morphinan biogenesis. These included inmobilisation of cells and changes in the growth medium. Morphinans were absent from unspecialised cells in all but one instance. The biotransformation of thebaine was tested in cell suspensions of P. somniferum and Nicotiana alata. Using thebaine (biosynthesised from CO2) these experiments were extended to organs of the P. somniferum plant. A thebaine-biotransfomation product arose in N. alata (but not P. somniferum) suspensions that also arose in excised P. somniferum capsules. A non-specific enzymic activity is proposed. No codeine or morphine were produced. Plant regeneration was demonstrated, in good yield, by embryogenesis fron meristenoid tissue of P. bracteatum. In P. somniferum the process was initiated but was not routinely successful. Regeneration may be useful for plant improvenent via cloning or as a source of variation. On reorganisation into plantlets, capacity for morphinan alkaloid accumulation was realised. Capacity for alkaloid accumulation is discussed in tenns of a requisite minimum level of cytodifferentiation, perhaps of laticifer-like cells. The uptake or binding of radiolabelled morphine by suspension cultures was investigated, since binding may be a reason for failure to detect morphinans in cultures extracted by the usual methods. Evidence was found that exogenous morphine binds to an insoluble fraction in P. somniferum and I. tabacum but cells did not contain any endogenous bound morphincins.
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Techapinyawat, Rheana. „The Evolution of Opium and Anesthesia: From the Ancient Sumerians to 1800s“. The University of Arizona, 2018. http://hdl.handle.net/10150/626597.
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Poppe, Frederik [Verfasser]. „Künstler mit Assistenzbedarf : Eine Interaktionsstudie / Frederik Poppe“. Frankfurt : Peter Lang GmbH, Internationaler Verlag der Wissenschaften, 2012. http://d-nb.info/1042414254/34.
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Poppe, Silvio [Verfasser]. „Selbstorganisation π-förmiger bolapolyphiler Catecholderivate / Silvio Poppe“. Halle, 2018. http://d-nb.info/1166140652/34.
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Schwarz, Stephan, und Gisela Schwarz. „750 Jahre Familiengeschichte Schwarz und Popp“. Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-100345.
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Vorliegendes Buch erzählt die Familiengeschichte der sächsischen Familien Schwarz und Popp. Der Autor hat sowohl seine Vorfahren, nämlich die Familienlinien Schwarz, Einenkel , Schulze und Dehmel, als auch die Vorfahren seiner Frau, nämlich die Familienlinien Popp, Kießling, Störl und Rüdiger bis Mitte des 13. Jahrhunderts - überwiegend anhand von Kirchenbucheinträgen - erforscht und beschrieben.
Die Familien stammen alle aus dem Erzgebirge und dem Vogtland. Einzelne Personen kamen aus Böhmen, Franken, Österreich und Baden-Württemberg hinzu.
Im ersten Teil sind die Herkunft der Familien, die Berufe, herausragende Persönlichkeiten, Besonderheiten aus dem Leben der Personen, sowie tragische und kuriose Geschichten aus den Kirchenbucheinträgen zusammengetragen. Außerdem sind, zugeordnet zu den Familien, tabellarische Aufstellungen von Herkunftsorten und Familiennamen enthalten.
Im Anhang Teil 2 sind die Ahnentafeln der Linien Schwarz und Popp dargestellt. Teil 3 enthält nochmals eine umfassende Aufstellung aller Herkunftsorte und Familiennamen.
Der Autor wurde 1947 in Limbach-Oberfrohna geboren, absolvierte Schul- und Berufsausbildung ab 1954 in Oberschwaben, ist seit 1970 verheiratet und lebt seit 1972 in Bayern.
Die Anlagen 1-12 auf den Seiten 53-218 sind in dem Online-Dokument aus rechtlichen Gründen nicht enthalten.
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Simms, Daniel M. „Remote sensing of opium poppy cultivation in Afghanistan“. Thesis, Cranfield University, 2016. http://dspace.lib.cranfield.ac.uk/handle/1826/9851.
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This work investigates differences in the survey methodologies of the monitoring programmes of the United Nations Office on Drugs and Crime (UNODC) and the US Government that lead to discrepancies in quantitative information about poppy cultivation. The aim of the research is to improve annual estimates of opium production. Scientific trials conducted for the UK Government (2006–2009) revealed differences between the two surveys that could account for the inconsistency in results. These related to the image interpretation of poppy from very high resolution satellite imagery, the mapping of the total area of agriculture and stratification using full coverage medium resolution imagery. MODIS time-series profiles of Normalised Difference Vegetation Index (NDVI), used to monitor Afghanistan’s agricultural system, revealed significant variation in the agriculture area between years caused by land management practices and expansion into new areas. Image interpretation of crops was investigated as a source of bias within the sample using increasing levels of generalisation in sample interpretations. Automatic segmentation and object-based classification were tested as methods to improve consistency. Generalisation was found to bias final estimates of poppy up to 14%. Segments were consistent with manual field delineations but object-based classification caused a systematic labelling error. The findings show differences in survey estimates based on interpretation keys and the resolution of imagery, which is compounded in areas of marginal agriculture or years with poor crop establishment. Stratified and unstratified poppy cultivation estimates were made using buffered and unbuffered agricultural masks at resolutions of 20, 30 and 60 m, resampled from SPOT-5 10 m data. The number of strata (1, 4, 8, 13, 23, 40) and sample fraction (0.2 to 2%) used in the estimate were also investigated. Decreasing the resolution of the imagery and buffering increased unstratified estimates. Stratified estimates were more robust to changes in sample size and distribution. The mapping of the agricultural area explained differences in cultivation figures of the opium monitoring programmes in Afghanistan. Supporting methods for yield estimation for opium poppy were investigated at field sites in the UK in 2004, 2005 and 2010. Good empirical relationships were found between NDVI and the yield indicators of mature capsule volume and dry capsule yield. The results suggested a generalised relationship across all sampled fields and years (R2 >0.70) during the 3–4 week period including poppy flowering. The application of this approach in Afghanistan was investigated using VHR satellite imagery and yield data from the UNODC’s annual survey. Initial results indicated the potential of improved yield estimates using a smaller and targeted collection of ground observations as an alternative to random sampling. The recommendations for poppy cultivation surveys are: the use of image-based stratification for improved precision and reducing differences in the agricultural mask, and use of automatic segmentation for improved consistency in field delineation of poppy crops. The findings have wider implications for improved confidence in statistical estimates from remote sensing methodologies.
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Wheeler, Mike. „An investigation into the molecular genetics and cytogenetics of self-incompatibility in Papaver rhoeas L“. Thesis, University of Birmingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367621.
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Carter, Karen Faye. „Description and control of flowering in California Poppy (Eschscholzia californica)“. Thesis, Virginia Polytechnic Institute and State University, 1986. http://hdl.handle.net/10919/53095.
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The California poppy (Eschscholzia californica Cham.) has floral marketplace potential provided it can be produced as a well-proportioned potted plant. Its attractive floral display and tolerance of extreme heat and drought make it a good candidate for research aimed at introducing it as a new ornamental crop.
The major objectives of this study were to document the apical meristem changes of California poppy during the transition to flowering, to determine the minimum number of inductive long-day (LD) cycles required for induction and initiation of flowering, and to examine the effects of exogenously applied gibberellin (GA₄₊₇) and auxin (NAA) on reproductive and vegetative development.
Histological examination of apical meristems exposed to varying numbers of LD cycles revealed many changes commonly associated with the onset of flowering. There was an increase in RNA activity in the apical cells, an enhanced doming of the shoot apex, an increased elongation of primordia internodes, a disruption of the tunica-corpus organization, and the appearance of well-developed branch primordia.
Eight to ten LD cycles was identified as the critical range required for successful flowering in California poppy plants when exposure to the inductive photoperiod was begun at the 8 to 12 true, expanded leaf stage.
Exogeneous NAA was shown to have no significant effect on final reproductive status or vegetative development of California poppy. GA₄₊₇ application resulted in an enhanced shift toward reproductive development and an increase in stem elongation, but it had little effect on peduncle elongation. These results indicate that stem and peduncle elongation may be controlled by different mechanisms and warrant further research.
The final chapter of the thesis concerning the design and evaluation of educational programs for the Virginia Tech Horticultural Gardens represents a departure from the major topic of study. This chapter is the result of the author's interest in, and the Garden's need for, an educational program suitable for the general public. This study can be considered the first step in the development of such an educational program.Master of Science
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Eklund, Jonas. „Fenomenet Poppe, mellan scen och skratt : En studie av Nils Poppes komiska skådespeleri utifrån en fenomenologisk utgångspunkt“. Thesis, Stockholms universitet, Avdelningen för teater- och dansvetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-90328.
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Scholarly research on comical popular theatre is rare in the Swedish context even though the genre has attracted large audiences throughout the 20th century. Nils Poppe is one of the greatest Swedish actors in the comical genre and he is famous for his playful acting style. With my Master’s dissertation I aim to shed some light on both the genre and this great actor. Another aim of this Master’s dissertation is to gain understanding of what causes the audience’s laughter experiencing Nils Poppe’s comical acting. To understand the audience response to the comical acting I need to study the communication between the actor and the beholders. In doing this I use Bert O. States phenomenological approach, in which he divides the communication into three modes in which the beholder experiences the action. In each of these modes I then use complementary concepts and theories to analyze the audience’s laughter. My analysis starts with the Representational mode in which the focus is on the fiction of the play. Using semiotics, I discuss Poppe’s characters as a stock character related to the Commedia dell’arte character Harlequin and other clown characters, which are imbedded in the audience’s memory. With examples from a play I show why the audience laugh in different scenes. In the next chapter, I analyze the Self-expressive mode in which the artist at stage is in focus. While experiencing the fiction of the play the audience simultaneously experiences the reality on stage. The actor is present and Poppe’s real face, body and voice is affecting the audience’s response. The final mode is the Collaborative mode in which the collaboration between the actor and beholder is analyzed. The direction of the play and how Poppe interacts with the audience is increasing the impression of presence among the audience. In his acting, Poppe breaks the theatrical conventions of the separation between fiction and reality, and in improvisations, he challenges both the audience and fellow actor’s notion of theatre. The result of the study implies that some laughter can’t be explained just by studying each of these modes separately. When the character leaves the fictional play and acts within the audience reality, or when the actor on stage is understood as part of the fiction an incongruity is created that tends to make the audience laugh.
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Poppe, Robert [Verfasser], und Markus [Akademischer Betreuer] Frölich. „Essays in Development Economics / Robert Poppe. Betreuer: Markus Frölich“. Mannheim : Universitätsbibliothek Mannheim, 2012. http://d-nb.info/1034490079/34.
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Garrett, Elizabeth Carol Bass. „Height control of Eschscholtzia californica using ancymidol, cycocel, and limited inductive photoperiod“. Thesis, Virginia Tech, 1988. http://hdl.handle.net/10919/43860.
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Limited inductive photoperiod (LIP) significantly reduced stem length but had no effect on the peduncle length, leaf number, plant diameter, days from seed to first flower or days from start of long days (LD) to first flower in Eschscholtzia californica. However with fewer LD cycles, negative effects associated with LIP included an increasing number of bud abortions and plants remaining vegetative, while the number of axillary buds decreased. Ancymidol [alpha-cyclopropyl-alpha-(4-methoxyphenyl)-5- pyrimidinemethanol] at 35, 45 and 50 ppm reduced stem length, but had no effect on peduncle length. Although plant diameter was significantly reduced, ancymidol had no effect on number of leaves or days to flower. There were no bud abortions, all plants flowered successfully, and there was no negative effect on axillary bud number with the use of ancymidol. Cycocel [(2-chloroethyl) trimethylammonium chloride] had no effect on stem length or the overall plant height in the Eschscholtzia californica. In addition, cycocel proved to be ineffective on associated vegetative growth and reproductive development.
Master of Science
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Popp, Alexander [Verfasser]. „Untersuchung von Peptiddynamik mittels zeitaufgelöster Infrarotspektroskopie / Alexander Popp“. Konstanz : Bibliothek der Universität Konstanz, 2015. http://d-nb.info/109943677X/34.
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Popp, Martin [Verfasser]. „Die strafrechtliche Verantwortung von Internet-Providern. / Martin Popp“. Berlin : Duncker & Humblot, 2002. http://d-nb.info/123831855X/34.
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Johnson, Alison G. „Functional architecture of alkaloid biosynthetic gene promoters from opium poppy“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ31356.pdf.
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Emery, Isabelle R. „Poppy dancer, illness and suicide : auto/biographically represented and critically analyzed“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ49563.pdf.
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Ontaneda, Elizabeth. „Crítica del libro Creating the Market de Elizabeth Popp Berman“. Universidad Peruana de Ciencias Aplicadas (UPC), 2014. http://hdl.handle.net/10757/332726.
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Critica del libro Creating the Market University: how academic science became economic engine en la cual Elizabeth Popp Berman analiza cómo universidades estadounidenses pasaron de ser generadores pasivos de conocimiento para el mercado a integrarse como actores claves del mercado a fines de los setentas.
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Poppek, Matthias [Verfasser]. „Diversität und Verbreitung von Schluchtwäldern (Tilio-Acerion) im Rheinischen Schiefergebirge / Matthias Poppek“. Koblenz : Universitätsbibliothek Koblenz, 2012. http://d-nb.info/1028947526/34.
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Zimmermann, Claudia [Verfasser], und Erich [Akademischer Betreuer] Poppe. „Ystoryaeu Seint Greal - Zwischen Übersetzung und Adaption / Claudia Zimmermann ; Betreuer: Erich Poppe“. Marburg : Philipps-Universität Marburg, 2021. http://d-nb.info/1230552669/34.
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Poppe, Michael [Verfasser]. „Untersuchung der humanen Coronavirus-induzierten Wirtsreaktion auf mRNA- und Proteomebene / Michael Poppe“. Gießen : Universitätsbibliothek, 2018. http://d-nb.info/116715892X/34.
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Almeida, Rebeca Alves Domingues Pereira de. „Plano de comunicação integrada de marketing para a marca Mariana Poppe Cêramica“. Master's thesis, Instituto Superior de Economia e Gestão, 2019. http://hdl.handle.net/10400.5/19330.
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Mestrado em MarketingA comunicação integrada de marketing (CIM) é uma ferramenta essencial para qualquer tipo de empresa pois tem como principal missão unificar, de maneira consistente e relevante, todos os formatos de comunicação que a empresa tem com os seus stakeholders. A eficiência da CIM garante às empresas uma comunicação clara e objetiva que tem um impacto positivo no alcance dos resultados pretendidos. Com este mote, o desenvolvimento deste projeto partiu da análise de uma marca de cerâmicas recente e com grande potencial de crescimento - Mariana Poppe Cerâmica - para, posteriormente, implementar um plano de comunicação integrada de marketing. A estratégia adotada na construção deste projeto foi a Case Study Research. Esta estratégia de pesquisa consiste na análise de pessoas, grupos, eventos, organizações ou outros sistemas que são estudados de forma holística por um ou mais métodos. Foram recolhidos dados secundários sobre o setor de atividade da empresa e toda a sua envolvente externa, bem como, dados primários, recolhidos através do formato de entrevistas semi-estruturadas realizadas à responsável da marca e aos seus stakeholders, com o objetivo de reunir informações que permitam melhorar o conhecimento do negócio. Sendo esta uma empresa que se encontra de momento numa fase inicial e com recursos limitados, o principal contributo é fornecer uma orientação prática com um plano de comunicação integrada que passará pelo desenvolvimento de várias áreas de atuação com o intuito de otimizar a comunicação da empresa.
Integrated marketing communications (IMC) is an essential tool for any type of company because its main mission is to unify, in a consistent and relevant way, all communication formats between the company and its stakeholders. The efficiency of IMC guarantees a clear and objective communication for companies, which has a positive impact on the achievement of the intended results. With this motto in mind, the development of this project stemmed from the analyses of a new pottery brand with great potential for growth - Mariana Poppe Cerâmica - with the purpose of implementing an integrated marketing communication plan afterward. The research strategy adopted in this project was a Case Study Research. This type of research strategy consists in analyzing people, groups, events, organizations or other systems which are studied in a holistic manner using one or more methods. Secondary data about the company's sector and its external context were collected. Primary data was also collected through semi-structured interviews with the owner of the brand and its stakeholders, in order to improve the knowledge regarding the business. Being a company that is currently in an initial phase and with limited resources, the main contribution will be to provide a practical orientation with an integrated communication plan that will involve the development of several areas of action in order to optimize the communication of the company.
info:eu-repo/semantics/publishedVersion
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Žilinskaitė, Dovilė. „TAPYBA ANT ŠILKO „AGUONŲ PIEVA”“. Bachelor's thesis, Lithuanian Academic Libraries Network (LABT), 2010. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2010~D_20100903_115229-82033.
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SANTRAUKA
Tapyba ant šilko – tai menas, artimas jausmams. Ši technologija atsirado Kinijoje ir paplito po visą pasaulį, tik kiekviena tauta tapybą ant šilko suprato ir interpretavo savaip. Tapyba ant šilko šiandien yra labai populiarus ir mielas užsiėmimas. Tapybos ant šilko tecnikos domina ne tik menininkus, bet ir moteris, moytojus bei moksleives. Šis užsiėmimas koordinuoja mokinių veiklą, kuri sužadina smalsumą, aktyvumą, skatina mąstymą.
Taigi mano darbo tema: Tapyba ant šilko „Aguonų pieva”. Pasirinkau šį augalo motyvą, nes aguonos – išlikimo ir trapumo simbolis, kuris rečiau sutinkamas lietuvių ornamentikoje, o tai dar labiau paskatino pasidomėti būtent aguonų motyvo tapyba.
Darbo tikslas: Paanalizuoti aguonos augalą istorijoje, mitologijoje, simbolikoje, tautosakoje ir
pavaizduoti jį tapant ant šilko.
Darbo uždaviniai:
Panagrinėti aguonos augalo atsiradimo istoriją, simboliką.
Paanalizuoti aguonos žiedo reikšmę mitologijoje, tautosakoje.
Panagrinėti aguonų neigiamą ir teigiamą poveikį žmogaus sveikatai.
Apžvelgti tapybos ant šilko istoriją ir technikas.
Paanalizuoti tapybos ant šilko technikų panaudojimą technologijų pamokose.
Atlikti kūrybinį darbą „Aguonų pieva“.
Metodai. Informacinių šaltinių analizė, mokinių pasiekimų analizė technologijų pamokose, kūrybinis darbas.
Šiame darbe aprašomas kūrybinio darbo atlikimas. Savo kūrybiniame darbe pasirinkau vaizduoti aguonų pievą. Aguonų pievos kompoziciją sudaro trys dalys. Sustačius visas tris kompozicijas į vieną... [toliau žr. visą tekstą]SUMMARY Painting on silk - is the art of close feelings. This technology emerged in China and has spread all over the world, but every nation understood the painting on silk and interpreted it in their own way. Paintings on silk are very popular and lovely occupation. Not only artists, but women, teachers and students are interested about painting on silk. This activity coordinates the activities of students, which stimulates curiosity, activity, stimulate thinking. So, my work theme is: Painting on silk “Poppy meadow”. I chose this motif of a plant, because poppy - a symbol of survival and fragility, which is less frequently encountered in Lithuanian ornamentation and this reason, further encouraged finding out precisely poppy motif paintings. Work aim: to analyze the poppy crop in history, mythology, symbolism, and folklore represented by painting on silk. Work tasks: To explore the history and symbolism of poppy plants; To analyze the significance of poppies ring in mythology and folklore; To explore the poppy negative and positive effects for human health; To review the history and techniques of painting on silk; To analyze the techniques of painting on silk adaptation in technology lessons; To do a creative work: “ Poppy meadow”. Work methods: Information Resource analysis; student achievement analysis in technology lessons, creative work. This work describes the performance of creative work. I decided to paint a poppy meadow. The composition of... [to full text]
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Gerardi, Richard David, und mikewood@deakin edu au. „Investigations into the analytical applications and fundamental chemistry of the chemiluminescent reactions of Tris(22-bipyridyl)ruthenium(III) with certain Papaver Somniferum alkaloids and other related compounds“. Deakin University. School of Biological and Chemical Sciences, 1999. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20060630.100432.
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The reaction of tris(2,2-bipyridyl)ruthenium(III) (Ru(bipy) 33+) with various analytes to generate chemiluminescence has been well documented. This investigation sought to undertake a chemiluminometic study of the reactions of Ru(bipy) 33+ with selected Papaver Somniferum alkaloids and specifically synthesised phenethylamines. The investigation, based on a kinetic study, primarily addressed the effect of varying reaction conditions (pH) on Ru(bipy) 33+ chemiluminescence production. To monitor these reactions, a batch chemiluminometer was specifically designed, fabricated and automated to conduct an extensive study on the selected compounds of interest. The instrumentation incorporated a custom built reaction cell and comprised an on-line sample preparation system with which calibration standards could be automatically prepared. The instrumentation provided both time-independent (peak area) and time-dependent (kinetic profile) information. A novel approach to the stabilisation of Ru(bipy) 33+ as a chemiluminescencent reagent was also investigated and a recirculating system was employed with the batch chemiluminometer to provide a stable supply of Ru(bipy) 33+. Codeine, thebaine and 6-methoxy-codeine were the Papaver Somniferum alkaloids selected for this study and several N-methylated and N,N-dimethylated phenethylamines and methoxy-substituted phenetheylamines were also synthesised to investigate the affect of pH on the chemiluminescence emission efficiency.
The versatility of the batch chemiluminometer facilitated the kinetic study of numerous analytes over a broad pH range. The exemplary performance of the chemiluminometer as an analytical instrument, was demonstrated by the calibration functions, based on peak area data, which exhibited excellent linearity and sensitivity. The estimated detection limits (3σ) for the selected alkaloids were in the range 2 x 10&-9<&/sup;> M to 7 x 10&-9<&/sup;> at pH 5.0 and above, which compared favourably to detection limits for the same compounds determined using FIA. Relative standard deviations (n=5) for peak areas ranged between 1% to 5% with a mean of 3.1% for all calibration standards above 2.5 x 10&-8<&/sup;> M. Correlation between concentration and peak area, irrespective of pH and analyte was excellent, with all but two calibration functions having r-squared values greater than 0.990. The analytical figures of merit exemplified the precision and robustness of the reagent delivery and on-line sample preparation, as well as the sensitivity of the system. The employment of the chemiluminometer for the measurement of total chemiluminescence emission (peak area) was in itself a feasible analytical technique, which generated highly reproducible and consistent data. Excellent analytical figures of merit, based on peak area, were similarly achieved for the phenethylamines.
The effects of analyte structure on chemiluminescence activity was also investigated for the alkaloids and the phenethylamines. Subtle structural variations between the three alkaloids resulted in either a moderately reduced or enhanced total emission that was two or three fold difference only. A significant difference in reaction kinetics was observed between thebaine and codeine/6-methoxy-codeine, which was dependent upon pH. The time-dependent data, namely the observed rate constants for the initial rise in intensity and for the subsequent decay rate, were obtained by fitting a mathematical function (based on the postulated reaction mechanism) to the raw data. The determination of these rate constants for chemiluminescence reactions highlighted the feasibility for utilising such measurements for quantitative analytical applications. The kinetic data were used to discriminate between analyte responses in order to determine the concentrations of individual analytes in a binary mixture. A preliminary, multi-component investigation performed on a binary mixture of codeine and 6-methoxy-codeine (1:1) successfully determined the concentrations of these individual components using such rate constant measurements.
Consequently, variations in kinetics resulted in a significant difference between the relative chemiluminescence response based on peak area measurements and the relative response base on peak height measurements obtained using FIA. With regards to the observed reactivity of secondary amines and tertiary amines, chemiluminescence peak area determinations confirmed the vital role of pH on reaction efficiency, which was governed by structural features and kinetics. The tertiary amines investigated generally produced a greater emission under acidic conditions than the corresponding secondary amines. However, the measured chemiluminescence responses were highly dependent upon pH, with similar peak areas obtained for both amine groups under slightly alkaline conditions.
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Boman, Johanna, und Josephine Ekhager. „Hur bra är bra tills bra blir dåligt?“ Thesis, Högskolan i Gävle, Avdelningen för ekonomi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-34173.
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Gevenkiris, Ali. „Determination Of Morphine And Total Phenolic Content In Poppy Seed Of Turkish Origin“. Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613052/index.pdf.
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Turkey is important major licid opium poppy (Papaver Somniferum) producer for medicinal and scientific purposes in the world and one of the two traditional producer country. The poppy seeds which are unique part of the opium poppy are used for food purpose. About 25.000 ton/year poppy seeds
were produced for food purpose. Recent years morphine content of commercially available poppy seeds were speculated. Some studies have been reported that poppy seeds from different origins contain a wide variation
of morphine (2 &ndash294) &mu
g/g content. They have been used also different sample preparation method (extraction and derivatization) and different instruments (GC-MS) during analyses. In this study morphine content was determined in Turkish origin which were white, yellow and blue poppy seeds colors by using high pressure liquid chromatography (HPLC). Different sample preparation method (without derivatization) was used. Morphine was eluted from poppy seeds by acidic water through stationary phase activated aluminum oxide. Poppy seed samples were collected from 13 provinces and 35 different sowing fields of Turkey. The determined morphine contents in poppy seeds were ranged between (9.73 to 37.46) &mu
g/g. Any study was not found in the literatures on determination of total phenolic in poppy seed. In this study, the optimum condition for extraction of polyphenols in poppy seeds was determined and then, total phenolic values were obtained in three different colours seeds by spectrophotometric method. At the end of experiments the total phenolic contents in white, yellow and blue colours poppy seed were found to be 4.44, 3.05 and 3.67 mg/g respectively.
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Poppe, Marco [Verfasser]. „Komplexe Mesophasen bolapolyphiler Moleküle mit Oligo(p-phenylenethinylen)-Gerüsten : [kumulative Dissertation] / Marco Poppe“. Halle, 2018. http://d-nb.info/1174205318/34.
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Karemo, Emil, und Viktor Svensson. „Poppa till det pedagogiskt! : en intervjustudie om fritidspedagogers uppfattningar kring populärkulturen på fritidshemmet“. Thesis, Högskolan Kristianstad, Fakulteten för lärarutbildning, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-18023.
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Syftet med studien är att undersöka fritidspedagogers uppfattningar kring elevers populärkultur och hur fritidspedagogerna beskriver att de arbetar med populärkulturen. Studien utgår från en fenomenografisk ansats. Intervjusvar från fritidspedagoger tolkades och delades in i olika kategorier. Forskningen visar att populärkulturen är ett brett område vilket gör populärkulturen till ett svårtolkat fenomen. Studien indikerar en stor variation i hur fritidspedagoger uppfattar och arbetar med elevernas populärkultur. Utifrån fritidspedagogernas berättelser framkom det att fritidspedagogerna hade svårigheter i att beskriva vad populärkultur är för något. Fritidspedagogerna vid de tre undersökta fritidshemmen beskriver alla olika uppfattningar om barns populärkultur. I analysen urskiljs följande kategorier som relevanta: fritidspedagogernas uppfattningar om populärkulturen, den digitala världen, den förbjudna världen, populärkulturen som forum för den sociala utvecklingen, det informella lärandet, elevernas populärkultur formar fritidshemmets verksamhet samt nätetiken. Studiens tydligaste resultat visar att fritidspedagogerna ser en stor vinst i att använda sig av populärkulturen på fritidshemmet. Det finns också ett motstånd mot populärkulturen som identifierats i intervjusvaren.
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Poppe, Stephan [Verfasser], und Eva [Akademischer Betreuer] Stukenbrock. „Host specialization in the fungal plant pathogen Zymoseptoria tritici / Stephan Poppe. Betreuer: Eva Stukenbrock“. Marburg : Philipps-Universität Marburg, 2015. http://d-nb.info/1068315555/34.
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Yellina, Aravinda Lakshmi [Verfasser]. „Functional analysis of carpel developmental genes in California poppy (Eschscholzia californica) / Aravinda Lakshmi Yellina“. Gießen : Universitätsbibliothek, 2016. http://d-nb.info/1119009537/34.
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Wäsche, Charlotte. „Vom Singen im Volke : Richard Poppe (1884-1960) und die Ideale des Finkensteiner Bundes /“. Weikersheim : Margraf, 2007. http://deposit.d-nb.de/cgi-bin/dokserv?id=3026869&prov=M&dok_var=1&dok_ext=htm.
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Delga, Alice. „L'effecteur PopP2 de Ralstonia solanacearum cible GTE9 et GTE11, deux lecteurs épigénétiques d'Arabidopsis thaliana“. Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30348.
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Les bactéries phytopathogènes produisent des effecteurs de type III qui sont des facteurs de virulence injectés dans la cellule hôte afin de moduler les défenses et ainsi favoriser l'infection. L'effecteur PopP2 de Ralstonia solanacearum possède une activité acétyl-transférase qui est perçue par la paire de protéines de résistance RRS1-R et RPS4 dans le noyau des cellules végétales. Cette étape de perception conduit à l'activation des réponses de défenses. GTE9 et GTE11, deux protéines à bromodomaine d'Arabidopsis thaliana, s'apparentent à des lecteurs épigénétiques ciblés par PopP2. Nos données démontrent que ces protéines GTEs (i) interagissent avec PopP2 dans le noyau des cellules végétales et (ii) sont acétylées en présence de l'effecteur. De plus, GTE9 et GTE11 se lient in vivo et in vitro à des histones H4, suggérant que PopP2 interfère avec des processus de remodelage de la chromatineMicrobial pathogens infect host cells by delivering virulence factors (effectors) that interfere with defenses, thereby favouring infection. The Ralstonia solanacearum PopP2 effector displays an acetyltransferase activity perceived by the Arabidopsis immune receptor pair, RRS1-R with RPS4, in the plant nucleus. This recognition step leads to the activation of immunity. Two Arabidopsis bromodomain-containing proteins , called General Transcription factor with Extra-terminal domain 9 and 11 (GTE9 and GTE11), were identified as PopP2-interacting partners. GTE9 and GTE11 are considered as epigenetic readers. Our data demonstrate that these GTEs proteins (i) interact with PopP2 in the plant nucleus and (ii) are acetylated in presence of the effector. Moreover, bromodomains of GTE9 and GTE11 bind in vivo and in vitro to Histone H4. Together, these data suggest that PopP2, through the targeting of GTE9 and GTE11, likely interfere with chromatin remodeling processes to affect ETS and/or ETI-related processes
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Theil, Frank [Verfasser], Benjamin [Akademischer Betreuer] Dietzek und Jürgen [Akademischer Betreuer] Popp. „Synthese und Charakterisierung artifizieller Reaktionszentren / Frank Theil. Gutachter: Benjamin Dietzek ; Jürgen Popp“. Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2014. http://d-nb.info/1062536304/34.
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Treffer, Regina [Verfasser], Volker [Akademischer Betreuer] Deckert und Jürgen [Akademischer Betreuer] Popp. „Nanoskopie zur Strukturaufklärung von DNA / Regina Treffer. Gutachter: Volker Deckert ; Jürgen Popp“. Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2014. http://d-nb.info/1047579235/34.
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Petzold, Felix [Verfasser], und Susanne [Akademischer Betreuer] Popp. „Historisches Lernen an materieller Religion im Museum / Felix Petzold ; Betreuer: Susanne Popp“. Augsburg : Universität Augsburg, 2020. http://d-nb.info/1226663788/34.
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Poppe, Michael [Verfasser]. „Integration von Infrastrukturen in Europa im historischen Vergleich : Band 5: Öl- und Treibstoffpipelines / Michael Poppe“. Baden-Baden : Nomos Verlagsgesellschaft mbH & Co. KG, 2015. http://d-nb.info/1106339444/34.
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Rey, Caballero Jordi. „Unravelling herbicide resistance in corn poppy (Papaver rhoeas L.) to improve integrated weed management strategies“. Doctoral thesis, Universitat de Lleida, 2016. http://hdl.handle.net/10803/382633.
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La presencia de biotipos de amapola (Papaver rhoeas L.) resistentes a herbicidas constituye uno de los principales problemas de muchas áreas cerealistas de secano. La solución del mismo pasa por una correcta caracterización de la resistencia y por el establecimiento de una adecuada estrategia de manejo integrado. El presente trabajo se ha planteado precisamente con este fin. Para ello a) se han seleccionado biotipos con resistencia múltiple (a inhibidores de la acetolactato sintasa -ALS- y a herbicidas auxínicos) y biotipos únicamente resistentes a 2,4-D originarios de las zonas cerealistas del noreste peninsular de los que se han estudiado las bases moleculares y fisiológicas de estas resistencias; b) se ha querido discernir bajo condiciones controladas (invernadero), si los fallos de control observados en campo, mediante herbicidas inhibidores del fotosistema II (bromoxinil), son debidos al estadio fenológico de la mala hierba en el momento de aplicación o a la presencia de una posible resistencia incipiente y c) se han establecido diferentes estrategias de manejo integrado de amapola en campos comerciales de cereales de secano del noreste peninsular.La presència de biotips de rosella (Papaver rhoeas L.) resistents a herbicides constitueix un dels principals problemes de moltes àrees cerealistes de secà. La solució del mateix passa per una correcta caracterització de la resistència així com en l'establiment d'una adequada estratègia de maneig integrat. El present treball s'ha plantejat precisament amb aquesta finalitat. Per això a) s'han seleccionat biotips amb resistència múltiple (a inhibidors de la acetolactato sintasa -ALS- i a herbicides auxínics) i biotips únicament resistents a 2,4-D originaris de les zones cerealistes del nord-est peninsular i s’han estudiat les bases moleculars i fisiològiques d'aquestes resistències; b) s'ha volgut discernir sota condicions controlades (hivernacle), si la manca de control observada en camp, mitjançant herbicides inhibidors del fotosistema II (bromoxinil), és deguda a l'estadi fenològic de la mala herba en el moment de l’aplicació o a la presència d' una possible resistència incipient i c) s'han establert diferents estratègies de maneig integrat de rosella en camps comercials de cereals de secà del nord-est peninsular.
The persistence of resistant corn poppy (Papaver rhoeas L.) biotypes is one of the most pressing problems in rainfed Spanish cereal crops. Resolution to this problem begins with the proper characterization of the resistant profile, followed by the establishment of an appropriate integrated management system. The study herein has been conducted precisely towards this end, while maintaining the following bases as a general framework: a) corn poppy biotypes with multiple resistance (acetolactate synthase -ALS- inhibiting herbicides and auxinic herbicides) and only 2,4-D resistance from north-eastern Spain were selected for analysis of molecular and physiological resistance matrices; b) we have tried to investigate under controlled conditions, if failures observed in the field, by photosystem II inhibiting herbicides (bromoxynil), could be directly attributed to the phenological stage of the weed at application time or inherent resistance and c) the creation of integrated management strategies for corn poppy and rainfed cereal fields in North-Eastern Spain.
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Poppe, Patrick [Verfasser], und Wolfgang [Akademischer Betreuer] Behringer. „„Translatio Europae?“ - Kulturelle Transferdiskurse im Kontext des Falls von Konstantinopel / Patrick Poppe ; Betreuer: Wolfgang Behringer“. Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1188238647/34.
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Popp, Hanna [Verfasser], und Martin [Gutachter] Herrmann. „Veränderung der Emotionsverarbeitung depressiver Patienten - eine EEG-Studie - / Hanna Popp ; Gutachter: Martin Herrmann“. Würzburg : Universität Würzburg, 2017. http://d-nb.info/1149510323/34.
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Bec, Julien [Verfasser], Jürgen [Gutachter] Popp und Laura [Gutachter] Marcu. „Intravascular Fluorescence lifetime characterization of Atherosclerosis / Julien Bec ; Gutachter: Jürgen Popp, Laura Marcu“. Jena : Friedrich-Schiller-Universität Jena, 2019. http://d-nb.info/1207273023/34.
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Popp, Andreas Verfasser], Heinrich [Akademischer Betreuer] [Kuhn und Ulrich [Akademischer Betreuer] Küsters. „Stochastische dynamische Losgrößenplanung mit positiven Bestellvorlaufzeiten / Andreas Popp. Betreuer: Heinrich Kuhn ; Ulrich Küsters“. Eichstätt-Ingolstadt : Katholische Universität Eichstätt-Ingolstadt, 2015. http://d-nb.info/1073584771/34.
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Popp, Andreas [Verfasser], Heinrich [Akademischer Betreuer] Kuhn und Ulrich [Akademischer Betreuer] Küsters. „Stochastische dynamische Losgrößenplanung mit positiven Bestellvorlaufzeiten / Andreas Popp. Betreuer: Heinrich Kuhn ; Ulrich Küsters“. Eichstätt-Ingolstadt : Katholische Universität Eichstätt-Ingolstadt, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:824-opus4-2543.
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Bartholmes, Conny. „Regulation of Morphogenesis of Lateral Organs in the Basal Eudicot Eschscholzia californica“. Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1305123248.
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Poppe, Jan [Verfasser], Stephen G. [Akademischer Betreuer] Hickey, Alexander [Akademischer Betreuer] Eychmüller und Thomas [Akademischer Betreuer] Wolff. „Spectroelectrochemical Investigations of Semiconductor Nanoparticles / Jan Poppe. Gutachter: Alexander Eychmüller ; Thomas Wolff. Betreuer: Stephen G. Hickey“. Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1071785575/34.
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