Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet. / Härtill 6 uppsatser.

A method for the retrieval of grain boundary inclination parameters of the grain boundary character distribution by oblique double-sectioning is proposed. The method, which is similar to the recovery of the orientation distributions from sets of incomplete pole-figures, is described along with a framework for implementation. The method directly measures grain boundary inclinations in a manner similar to serial sectioning while statistically sampling the microstructure comparably to stereological methods. Computer simulations of the method were used to confirm the mathematical framework. Additional simulations, where the grain boundary normal distributions were recovered by both oblique double-sectioning and stereological methods, showed that results recovered by 3 orthogonal double-sections from oblique double-sectioning proved to be just as accurate as the 25 section-cuts required for stereology in resolving the finer details in the recovered distribution.

No description available.

As copaíferas fazem parte de um importante gênero de plantas que produzem um exsudato denominado como oleorresina, que é constituído por uma mistura de sesquiterpenos e diterpenos ácidos. A medicina popular utiliza a oleorresina de diferentes espécies de Copaifera com diversas indicações, tais como: ação anti-inflamatória, antimicrobiana, cicatrizante, antitumoral, entre outras. Desta forma, numerosos pesquisadores têm investigado a composição química e as atividades biológicas e toxicológicas deste produto natural, a fim de reconhecer os benefícios e a segurança deste produto. Todavia, estudos da composição química e das atividades biológicas dos constituintes das folhas são escassos. Assim, neste projeto buscou-se investigar a composição química de diferentes extratos de folhas e de oleorresinas de copaíferas coletadas na flora brasileira, bem como produtos comerciais (óleo de copaíba) propondo e aplicando métodos analíticos em cromatografia para determinação dos principais constituintes das amostras. Dez amostras de folhas e oleorresinas autênticas de diferentes espécies foram coletadas no norte e sudeste do Brasil (C. langsdorffi Desf., C. duckei Dwyer, C. reticulata Ducke, C. multijuga Hayne, C. paupera (Herzog) Dwyer, C. pubiflora Benth, C. lucens Dwyer, C. oblogifolia Mart, C. trapezifolia Hayne, e Copaifera sp.) e mais seis amostras comerciais foram adquiridas. Os compostos voláteis foram separados da oleorresina bruta utilizando-se o aparelho de Clevenger. Os padrões cromatográficos foram isolados utilizando-se diferemntes modalidades cromatográficas. As oleorresinas de C. multijulga e C. langsdorffii apresentaram os maiores teores de óleo volátil das amostras com 92 e 72%, respectivamente. Três diterpenos foram isolados da oleorresina de C. duckei: os ácidos ent-poliáltico, ent-diidroagático e ent-agático-15-metil éster. Uma análise qualitativa foi otimizada usando microextração em fase sólida seguido de análise em CG-EM, a qual revelou a presença em comum do ?-copaeno, ?-elemeno, ?-cariofileno e ?-bergamoteno em todas as amostras de oleorresina analisadas. Dois métodos analíticos utilizando CLUE-EM/EM e CG-DIC foram desenvolvidos, otimizados e validados para análise de nove diterpenos ácidos e quatro sesquiterpenos, os quais apresentaram adequada seletividade/especificidade, faixa de trabalho, limite de detecção, limite de quantificação, precisão e exatidão. Todavia, em ambos os métodos há necessidade de controle rigoroso das condições analíticas dos sistemas cromatográficos. Os resultados obtidos aplicando os dois métodos indicaram a presença frequente do ?-cariofileno e dos ácidos ent-copálico e ent-caurenoico como as substâncias mais encontradas em oleorresinas de copaíferas autênticas e comerciais. A análise qualitativa empregando CLUE-EM indicou a presença dos ácidos di-O-metil-3,5-di-O-galoilquínico (AGQ-8), 5\',5\'\'-di-O-metil-4,5-di-O-galoilquínico (AGQ-9), 5\',5\'\',5\'\'\'-tri-O-metil-3,4,5-tri-O-galoilquínico (AGQ-16), afzelina e quercitrina nos extratos das folhas de nove amostras de copaíferas. Os métodos analíticos desenvolvidos são confiáveis para as análises dos componentes fixos e voláteis e os resultados obtidos neste trabalho confirmam a variabilidade da composição química das oleorresinas desse gênero vegetal. / Copaifera plants are part of an important genus that produces an exsudate called oleoresin, which consists of a mixture of sesquiterpenes and acid diterpenes. Folk medicine uses the oleoresin of different Copaifera species for different health problems, such as: anti-inflammatory, antimicrobial, wound healing and antitumor, among others. Thus, numerous researchers have investigated the chemical composition, biological and toxicological activities of this natural product in order to recognize its benefits and safety. However, investigation of chemical composition and biological activities of leaf contituents are scarce. In this project we aimed to investigate the chemical composition of different leaf extracts and Copaifera oleoresins collected in the Brazilian flora and acquired in the market (copaíba oil) by proposing and applying chromatographic analytical methods to determine their main constituents. Ten samples of leaves and authentic oleoresins of different species were collected in northern and southeastern parts of Brazil (C. langsdorffi Desf., C. duckei Dwyer, C. reticulata Ducke, C. multijuga Hayne, C. paupera (Herzog) Dwyer, C. pubiflora Benth, C. lucens Dwyer, C. oblogifolia Mart, C. trapezifolia Hayne, e Copaifera sp.) and six commercial samples were purchased. The volatile fraction of the crude oleoresin was obtained by using Clevenger apparatus, and the chromatographic standards were isolated by using different chromatographic techniques. The oleoresins of C. langsdorffii and C. multijuga displayed the highest volatile oil contents. Three diterpenes were isolated from C. duckei oleoresin: ent-polialthic, ent-dihydroagathic and ent-agathic-15-metil ester acids. A qualitative analysis was optimized using solid phase micro-extraction followed by GC-MS analysis, which revealed the presence of ?-copaene, ?-elemene, ?-caryophyllene and ?-bergamotene in all investigated oleoresins. Two analytical methods using UPLC-MS/MS and GC-FID were developed, optimized and validated for the analysis of nine acid diterpenes and four sesquiterpenes, which gave adequate selectivity/specificity, range, limit of detection, limit of quantification, precision and accuracy. However, in both methods there is a need for rigorous control of the analytical conditions. The results generated by the two methods indicated the frequent presence of ?-caryophyllene, ent-copalic and ent-kaurenoic acids as the compounds frequently found in authentic and commercial Copaifera oleoresins. Qualitative analysis of leaf extracts using UPLC-MS/MS indicated the presence of 5\',5\'\'-di-O-methyl-3,5-di-O-galloylquinic acid (GQA-8), 5\',5\'\'-di-O-methyl-4,5-di-O-galloylquinic acid (GQA-9), 5\',5\'\',5\'\'\'-tri-O-methyl-3,4,5-tri-O-galloylquinic acid (GQA-16), afzelin and quercetrin in all studied species. The analytical developed methods are reliable for the analyses of both fixed and volatile compounds of the oleoresins. The obtained results confirm the variability among the composition of the Copaifera oleoresins.

A síndrome da imunodeficiência adquirida é causada pelo vírus da imunodeficiência humana e é caracterizada por provocar depleção física e funcional do sistema imune do organismo, através da infecção citopática de células CD4+. Muitos fármacos anti-retrovirais tem sido desenvolvidos e estão disponíveis comercialmente. Para atuar no controle de qualidade de medicamentos deve-se continuamente estudar o desenvolvimento e a validação de novas metodologias para quantificação de fármacos, para serem aplicadas nos estudos de estabilidade de formulações farmacêuticas e na análise de produtos de degradação. Neste trabalho foram utilizadas duas técnicas analíticas, a espectrofotometria direta no UV/VIS e a cromatografia líquida de alta eficiência (CLAE), para a determinação quantitativa de zidovudina (AZT) e estavudina (d4T).em medicamentos. Ambos os métodos foram validados com relação à linearidade, exatidão, precisão, especificidade e limite de detecção e quantificação. O método validado para a CLAE foi também empregado para a determinação quantitativa da timina, produto de degradação do AZT e da d4T. A metodologia validada por CLAE foi utilizada na realização de estudos de estabilidade acelerada dos anti-retrovirais contidos nas diferentes preparações farmacêuticas. Realizou-se o estudo da estabilidade em três diferentes condições: temperatura ambiente, 40 oC / 75% UR e 50 oC / 90% UR. Tanto a zidovudina (Fabricante A) e estavudina (Fabricante B) apresentaram decaimento cinético de zero ordem com prazos de validade a 50 oC / 90% UR de 10, 3 e 2 meses, respectivamente. / The acquired immunodeficiency syndrome is characterized by causing physical and functional depletion of the organism’s immune system, through the cytophatic infection of CD4+ cells. Several antiretroviral drugs has been developed and commercially made available. In order to assure the quality control of drugs it is necessary to develop and validate new analytical methodologies to perform the quantitative determination of drugs and stability studies of pharmaceutical formulations by determining the drug itself and its degradation products. In this research two analytical techniques, direct UV/VIS spectrophotometry and high performance liquid chromatography (HPLC), were used for the quantitative determination of zidovudine (AZT) and stavudine (d4T) in pharmaceutical preparations. Both methods were validated and parameters like linearity, precision, accuracy, specificity, limit of detection and limit of quantification, were determined. The validated HPLC method was also applied for quantitative determination of timine, a degradation product of AZT and d4T. The validated HPLC method was applied to accelerate stability studies of AZT and d4T in different pharmaceutical preparations. The stability studies were performed at three different conditions: room temperature, 40 oC / 75% RH and 50 oC / 90% RH. Both AZT and d4T (Industry A) and d4T (Industry B) pharmaceutical preparations presented a zero order degradation reaction. The three formulations presented a shelf-life of 10, 3 and 2 months, respectively, at 50 oC / 90% RH.

Radiofármacos são compostos radioativos que podem ser usados tanto para diagnóstico como para terapia. O radiofármaco 99m-Tc-MIBI é a formação de um complexo contendo o radionúclideo Tecnécium-99m e seis moléculas de Sestamibi, usado principalmente para cintilografias do miocárdio, sendo o procedimento mais realizado dentro da medicina nuclear, por consequência, o radiofármaco mais comercializado. Já o radiofármaco 99m-Tc-DTPA é composto também pelo mesmo radioisótopo e por uma molécula de ácido pentético, a qual tem característica de um quelante com afinidade pelos rins, por isso, é possível fazer avaliação do sistema renal. Como os radiofármacos são considerados medicamentos, estão sujeitos às mesmas normativas, logo o objetivo deste trabalho foi desenvolver metodologia de doseamento destes insumos ativos antes da complexação com o radionuclídeo através da metodologia de Cromatografia Líquida de Alta Eficiência (CLAE). Dois métodos simples e eficientes foram desenvolvidos e validados para o MIBI em produto acabado e para a matéria-prima ácido pentético (DTPA), utilizando-se misturas de solvente orgânico e tampão. Os parâmetros de validação foram avaliados, obtendo resultados satisfatórios. Um teste de estabilidade para o radiofármaco MIBI em solução foi realizado e o resultado indicou uma preservação das características de aproximadamente 60 dias, e quando liofilizado de mais de 12 meses. Sendo assim, os métodos propostos foram considerados adequados para utilização na rotina da indústria farmacêutica. Como perspectivas, novas condições serão testadas para obter método de quantificação para o radiofármaco 99m-Tc-DTPA em produto acabado. / Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) sestamibi is a radiopharmaceutical including a coordination complex consisting of the radioisotope technetium-99m bound to six Sestamibi ligands, which is mainly used to image the myocardium via scintigraphy. This is the most common nuclear medicine procedure, making Technetium (99mTc) sestamibi the most commercialized radiopharmaceutical. Technetium (99mTC)-DTPA in turn is composed by the same radioisotope plus a molecule of Pentetic Acid, which, by its chelating properties, is used to scan renal system. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study is to develop quantification methodology for these both active pharmaceutical ingredients before their complexation with the radioisotope by employing high-performance liquid chromatography (HPLC) methodology. Two simple, efficient methods were developed and validated for Sestamibi at its final form as well as for DTPA's raw material by using buffer and organic solvent mixtures. The validation parameters were evaluated with satisfactory results. A stability test was carried out for Sestamibi, indicating the preservation of characteristics for nearly 60 days, and for over 12 months when at its freezedryed form. The proposed methods were thus considered adequate for pharmaceutical industries. As perspectives, new conditions shall be tested to obtain a quantification method for Technetium (99mTC)-DTPA at its final form.

Complex networks are ubiquitous in nature. Numerous neurological diseases, such as Alzheimer's, Parkinson's, epilepsy are caused by the abnormal collective behaviour of neurons in the brain. In particular, there is a strong evidence that Parkinson's disease is caused by the synchronisation of neurons, and understanding how and why such synchronisation occurs will bring scientists closer to the design and implementation of appropriate control to support desynchronisation required for the normal functioning of the brain. In order to study the emergence of (de)synchronisation, it is necessary first to understand how the dynamical behaviour of the system under consideration depends on the changes in systems parameters. This can be done using a powerful mathematical method, called bifurcation analysis, which allows one to identify and classify different dynamical regimes, such as, for example, stable/unstable steady states, Hopf and fold bifurcations, and find periodic solutions by varying parameters of the nonlinear system. In real-world systems, interactions between elements do not happen instantaneously due to a finite time of signal propagation, reaction times of individual elements, etc. Moreover, time delays are normally non-constant and may vary with time. This means that it is vital to introduce time delays in any realistic model of neural networks. In this thesis, I consider four different models. First, in order to analyse the fundamental properties of neural networks with time-delayed connections, I consider a system of four coupled nonlinear delay differential equations. This model represents a neural network, where one subsystem receives a delayed input from another subsystem. The exciting feature of this model is the combination of both discrete and distributed time delays, where distributed time delays represent the neural feedback between the two sub-systems, and the discrete delays describe neural interactions within each of the two subsystems. Stability properties are investigated for different commonly used distribution kernels, and the results are compared to the corresponding stability results for networks with no distributed delays. It is shown how approximations to the boundary of stability region of an equilibrium point can be obtained analytically for the cases of delta, uniform, and gamma delay distributions. Numerical techniques are used to investigate stability properties of the fully nonlinear system and confirm our analytical findings. In the second part of this thesis, I consider a globally coupled network composed of active (oscillatory) and inactive (non-oscillatory) oscillators with distributed time delayed coupling. Analytical conditions for the amplitude death, where the oscillations are quenched, are obtained in terms of the coupling strength, the ratio of inactive oscillators, the width of the uniformly distributed delay and the mean time delay for gamma distribution. The results show that for uniform distribution, by increasing both the width of the delay distribution and the ratio of inactive oscillators, the amplitude death region increases in the mean time delay and the coupling strength parameter space. In the case of the gamma distribution kernel, we find the amplitude death region in the space of the ratio of inactive oscillators, the mean time delay for gamma distribution, and the coupling strength for both weak and strong gamma distribution kernels. Furthermore, I analyse a model of the subthalamic nucleus (STN)-globus palidus (GP) network with three different transmission delays. A time-shift transformation reduces the model to a system with two time delays, for which the existence of a unique steady state is established. Conditions for stability of the steady state are derived in terms of system parameters and the time delays. Numerical stability analysis is performed using traceDDE and DDE-BIFTOOL in Matlab to investigate different dynamical regimes in the STN-GP model, and to obtain critical stability boundaries separating stable (healthy) and oscillatory (Parkinsonian-like) neural ring. Direct numerical simulations of the fully nonlinear system are performed to confirm analytical findings, and to illustrate different dynamical behaviours of the system. Finally, I consider a ring of n neurons coupled through the discrete and distributed time delays. I show that the amplitude death occurs in the symmetric (asymmetric) region depending on the even (odd) number of neurons in the ring neural system. Analytical conditions for linear stability of the trivial steady state are represented in a parameter space of the synaptic weight of the self-feedback and the coupling strength between the connected neurons, as well as in the space of the delayed self-feedback and the coupling strength between the neurons. It is shown that both Hopf and steady-state bifurcations may occur when the steady state loses its stability. Stability properties are also investigated for different commonly used distribution kernels, such as delta function and weak gamma distributions. Moreover, the obtained analytical results are confirmed by the numerical simulations of the fully nonlinear system.

Let Ω ⊂ Rn be a bounded Lipschitz domain and consider the energy functional F[u, Ω] := ∫ Ω F(∇u(x)) dx, over the space Ap(Ω) := {u ∈ W 1,p(Ω, Rn): u|∂Ω = x, det ∇u> 0 a.e. in Ω}, where the integrand F : Mn×n → R is quasiconvex, sufficiently regular and satisfies a p-coercivity and p-growth for some exponent p ∈ [1, ∞[. A motivation for the study of above energy functional comes from nonlinear elasticity where F represents the elastic energy of a homogeneous hyperelastic material and Ap(Ω) represents the space of orientation preserving deformations of Ω fixing the boundary pointwise. The aim of this thesis is to discuss the question of multiplicity versus uniqueness for extremals and strong local minimizers of F and the relation it bares to the domain topology. Our work, building upon previous works of others, explicitly and quantitatively confirms the significant role of domain topology, and provides explicit and new examples as well as methods for constructing such maps. Our approach for constructing strong local minimizers is topological in nature and is based on defining suitable homotopy classes in Ap(Ω) (for p ≥ n), whereby minimizing F on each class results in, modulo technicalities, a strong local minimizer. Here we work on a prototypical example of a topologically non-trivial domain, namely, a generalised annulus, Ω= {x ∈ Rn : a< |x| <b}, with 0 <a<b< ∞. Then the associated homotopy classes of Ap(Ω) are infinitely many when n =2 and two when n ≥ 3. In contrast, for constructing explicitly and directly solutions to the system of Euler-Lagrange equations associated to F we introduce a topological class of maps referred to as generalised twists and relate the problem to extremising an associated energy on the compact Lie group SO(n). The main result is a surprising discrepancy between even and odd dimensions. In even dimensions the latter system of equations admits infinitely many smooth solutions, modulo isometries, amongst such maps whereas in odd dimensions this number reduces to one. Even more surprising is the fact that in odd dimensions the functional F admits strong local minimizers yet no solution of the Euler-Lagrange equations can be in the form of a generalised twist. Thus the strong local minimizers here do not have the symmetry one intuitively expects!.

This thesis is concerned with the derivation, numerical analysis and implementation of high-order compact finite difference schemes for parabolic partial differential equations in multiple spatial dimensions. All those partial differential equations contain mixed derivative terms. The resulting schemes have been applied to equations appearing in computational finance. First, we develop and study essentially high-order compact finite difference schemes in a general setting with option pricing in stochastic volatility models on non-uniform grids as application. The schemes are fourth-order accurate in space and second-order accurate in time for vanishing correlation. In the numerical study we obtain high-order numerical convergence also for non-zero correlation and non-smooth payoffs which are typical in option pricing. In all numerical experiment a comparative standard second-order discretisation is significantly outperform. We conduct a numerical stability study which indicates unconditional stability of the scheme. Second, we derive and analyse high-order compact schemes with n-dimensional spatial domain in a general setting. We obtain fourth-order accuracy in space and second-order accuracy in time. A thorough von Newmann stability analysis is performed for spatial domain with dimensions two and three. We prove that a necessary stability condition holds unconditionally without additional restrictions on the choice of the discretisation parameters for vanishing mixed derivative terms. We also give partial results for non-vanishing mixed derivative terms. As first example Black-Scholes Basket options are considered. In all numerical experiments, where the initial conditions were smoothened using the smoothing operators developed by Kreiss, Thomée and Widlund, a comparative standard second-order discretisation is significantly outperformed. As second example the multi-dimentional Heston basket option is considered for n independent Heston processes, where for each Heston process there is a non-vanishing correlation between the stock and its volatility.

This research work is on time-delayed models of infectious diseases dynamics. The dynamics of infectious diseases are studied in the presence of time delays representing temporary immunity or latency. We have designed and analysed time-delayed models with various parameters to simulate disease dynamics, in a view to gaining insight into the behaviour of a population in the presence of infectious diseases, and the reaction of the population to changes in the management procedure of such infections.