980 resultados para lignan derivative


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E-Lychnophoric acid 1, its derivative ester 2 and alcohol 3 killed 100% of trypomastigote blood forms of Trypanosoma cruzi at the concentrations of 13.86, 5.68, and 6.48 µg/mL, respectively. Conformational distribution calculations (AM1) of 1, 2 and 3 gave minimum energies for the conformers a, b, c, and d, which differ from each other only in the cyclononene ring geometry. Calculations (DFT/BLYP/6-31G*) of geometry optimization and chemical properties were performed for conformers of 1, 2, and 3. The theoretical results were numerically compared to the trypanocidal activity. Calculated values of atomic charge, orbital population, and vibrational frequencies showed that the C-4-C-5 pi-endocyclic bond does not affect the trypanocidal activity of the studied compounds. Nevertheless, the structure of the group at C-4 strongly influences the activity. However, the theoretical results indicated that the intra-ring (C-1 and C-9) and pi-exocycle (C-8 and C-14) carbons of caryophyllene-type structures promote the trypanocidal activity of these compounds.

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Solid-state M-2-MeO-Bz compounds, where M stands for bivalent Mn, Co, Ni, Cu and Zn and 2-MeO-Bz is 2-methoxybenzoate, have been synthesized. Simultaneous thermogravimetry-differential thermal analysis (TG-DTA), thermogravimetry, derivative thermogravimetry (TG/DTG), differential scanning calorimetry (DSC), X-ray powder diffractometry, infrared spectroscopy and complexometry were used to characterize and to study the thermal behaviour of these compounds. The results led to have information about the composition, dehydration, thermal stability and thermal decomposition of the isolated compounds.

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Solid State Ln-L compounds, where Ln stands for light trivalent lanthanides (La - Gd) and L is pyruvate, have been synthesized. Thermogravimetry and derivative thermogravimetry (TG/DTG), differential scanning calorimetry (DSC), X-Ray powder diffractometry, infrared spectroscopy, elemental analysis, and complexometry were used to characterize and to study the thermal behaviour of these compounds. The results led to information about the composition, dehydration, ligand denticity, thermal behaviour and thermal decomposition of the isolated compounds.

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Solid state M-L compounds, were M stands for bivalent Mn, Fe, Co, Ni, Cu, Zn and L is pyruvate, have been synthesized. Thermogravimetry and derivative thermogravimetry (TG/DTG), differential scanning calorimetry (DSC), X-Ray powder diffractometry, infrared spectroscopy, elemental analysis, and complexometry were used to characterize and to study the thermal behaviour of these compounds. The results led to information about the composition, dehydration, ligand denticity, and thermal decomposition of the isolated compounds.

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Synthesis, electronic, infrared, elemental micro analytical studies were carried on N-(benzothiazol-2-yl)trichloroethanamide [4] and N-(benzothiazol-2-yl)chloroethanamide [5]. They were also screened in vitro and in vivo for antibacterial activity. The results indicate that the compounds are very stable and that they show high antibacterial activities against both gram-positive and gram-negative bacteria tested. Both derivatives of 2-aminobenzothiazole were active against the multiresistant bacteria with IZD ranging from 9 -18 mm [5] and 9 - 20mm [4]. From the MIC results it is observed that the [5] derivative produced a better antibacterial activity than the [4] derivative. The lethal concentrations (LC50) of the compounds were also determined. Their solubilities and melting points were also determined.

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Huoli ympäristön tilasta ja fossiilisten polttoaineiden hinnan nousu ovat vauhdittaneet tutkimusta uusien energialähteiden löytämiseksi. Polttokennot ovat yksi lupaavimmista tekniikoista etenkin hajautetun energiantuotannon, varavoimalaitosten sekä liikennevälineiden alueella. Polttokenno on tehonlähteenä kuitenkin hyvin epäideaalinen, ja se asettaa tehoelektroniikalle lukuisia erityisvaatimuksia. Polttokennon kytkeminen sähköverkkoon on tavallisesti toteutettu käyttämällä galvaanisesti erottavaa DC/DC hakkuria sekä vaihtosuuntaajaa sarjassa. Polttokennon kulumisen estämiseksi tehoelektroniikalta vaaditaan tarkkaa polttokennon lähtövirran hallintaa. Perinteisesti virran hallinta on toteutettu säätämällä hakkurin tulovirtaa PI (Proportional and Integral) tai PID (Proportional, Integral and Derivative) -säätimellä. Hakkurin epälineaarisuudesta johtuen tällainen ratkaisu ei välttämättä toimi kaukana linearisointipisteestä. Lisäksi perinteiset säätimet ovat herkkiä mallinnusvirheille. Tässä diplomityössä on esitetty polttokennon jännitettä nostavan hakkurin tilayhtälökeskiarvoistusmenetelmään perustuva malli, sekä malliin perustuva diskreettiaikainen integroiva liukuvan moodin säätö. Esitetty säätö on luonteeltaan epälineaarinen ja se soveltuu epälineaaristen ja heikosti tunnettujen järjestelmien säätämiseen.

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The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

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The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.

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The present study shows the development, simulation and actual implementation of a closed-loop controller based on fuzzy logic that is able to regulate and standardize the mass flow of a helical fertilizer applicator. The control algorithm was developed using MATLAB's Fuzzy Logic Toolbox. Both open and closed-loop simulations of the controller were performed in MATLAB's Simulink environment. The instantaneous deviation of the mass flow from the set point (SP), its derivative, the equipment´s translation velocity and acceleration were all used as input signals for the controller, whereas the voltage of the applicator's DC electric motor (DCEM) was driven by the controller as output signal. Calibration and validation of the rules and membership functions of the fuzzy logic were accomplished in the computer simulation phase, taking into account the system's response to SP changes. The mass flow variation coefficient, measured in experimental tests, ranged from 6.32 to 13.18%. The steady state error fell between -0.72 and 0.13g s-1 and the recorded average rise time of the system was 0.38 s. The implemented controller was able to both damp the oscillations in mass flow that are characteristic of helical fertilizer applicators, and to effectively respond to SP variations.

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Hawthorn (Crataegus sp.) is widely distributed in the northern hemisphere (Asia, Europe and North America). It has been used as a medicinal material and food for hundreds of years both in Europe and in China. Clinical investigations and other research suggest that extracts of hawthorn fruits and leaves have multiple health effects including hypolipidaemic, anti-atherosclerotic, hypotensive, cardioprotective and blood vessel relaxing activities. Hawthorn fruit extracts have also displayed antioxidant and radical scavenging activities. Emblic leafflower fruit (Phyllanthus emblica) is widely used in Chinese and Indian traditional medicine. It has been found to have anti-cancer, hypoglycaemic and hypolipidaemic activities as well as cardioprotective effects and antioxidant activity. The fruit is currently used as a functional food targeted at obese people in China. Phenolic compounds, procyanidins (PCs), flavonols and C-glycosyl flavones in hawthorn and hydrolysable tannins in emblic leafflower fruits are considered among the major bioactive compounds in these berries. Moreover, hawthorn and emblic leafflower fruits are rich in vitamin C, triterpenoids, fruit acids, sugar alcohols and some other components with beneficial effects on the health of human beings. The aim of the thesis work was to characterise the major phenolic compounds in hawthorn fruits and leaves and emblic leafflower fruits as well as other components contributing to the nutritional profile and sensory properties of hawthorn fruits. Differences in the content and compositional profile of the major phenolic compounds, sugars, acids and sugar alcohols within various origins and species of hawthorn were also investigated. Acids, sugars and sugar alcohols in the fruits of different origins/cultivars belonging to three species (C. pinnatifida, C. brettschneideri and C. scabrifolia) of hawthorn were analysed by gas chromatography (GC-FID) and mass spectrometry (Publication I). Citric acid, quinic acid, malic acid, fructose, glucose, sorbitol and myo-inositol were found in all the subspecies. Sucrose was present only in C. scabrifolia and three cultivars of C. pinnatifida var. major. Forty-two phenolic compounds were identified/tentatively identified in fruits of C. pinnatifida var. major by polyamide column chromatography combined with high-performance liquid chromatograph-electrospray ionisation mass spectrometry (HPLC-ESI-MS) (Publication II). Ideain, chlorogenic acid, procyanidin (PC) B2, (-)-epicatechin, hyperoside and isoquercitrin were the major phenolic components identified. In addition, 35 phenolic compounds were tentatively identified based on UV and mass spectra. Eleven major phenolic compounds (hyperoside, isoquercitrin, chlorogenic acid, ideain, (-)-epicatechin, two PC dimers, three PC trimers and a PC dimer-hexoside) were quantified in the fruits of 22 cultivars/origins of three species of Chinese hawthorn by HPLC-ESI-MS with single ion recording function (SIR) (Publication III). The fruits of the hawthorn cultivars/origins investigated fell into two groups, one rich in sugars and flavonols, the other rich in acids and procyanidins. Based on the compositional features, different biological activities and sensory properties may be expected between cultivars/origins of the two groups. The results suggest that the contents of phenolic compounds, acids, sugars and sugar alcohols may be used as chemotaxonomic information distinguishing the hawthorn species from each other. Phenolic compounds in fruits and leaves of C. grayana and their changes during fruit ripening/harvesting were investigated using HPLC-UV-ESI-MS (Publication IV). (-)-Epicatechin, PC B2 and C1, hyperoside and a quercetin-pentoside were the major phenolic compounds in both fruits and leaves. Three C-glycosyl flavones (a luteolin-C-hexoside, a methyl luteolin-C-hexoside and an apigenin-C-hexoside) were present in leaves in abundance, but only at trace levels in fruits. Ideain and 5-O-caffeoylquinic acid were found in fruits only. Additionally, eleven phenolic compounds were identified/tentatively identified in both leaves and fruits (three B-type PC trimers, two B-type PC tetramers, a quercetin-rhamnosylhexoside, a quercetin-pentoside, a methoxykaempferol-methylpentosylhexoside, a quercetin-hexoside acetate, a methoxykaempferol-pentoside, chlorogenic acid and an unknown hydroxycinnamic acid derivative). The total content of phenolic compounds reached the highest level by the end of August in fruits and by the end of September in leaves. The compositional profiles of phenolic compounds in fruits and leaves of C. grayana were different from those of C. pinnatifida, C. brettschneideri, C. scabrifolia, C. pinnatifida. var. major, C. monogyna, C. laevigata and C. pentagyna. Phenolic compounds in emblic leafflower fruits were characterised by Sephadex LH-20 column chromatography combined with HPLC-ESI-MS (Publication V). A mucic acid gallate, three isomers of mucic acid lactone gallate, a galloylglucose, gallic acid, a digalloylglucose, putranjivain A, a galloyl-HHDP-glucose, elaeocarpusin and chebulagic acid represented the major phenolic compounds in fruits of emblic leafflower. In conclusion, results of this study significantly increase the current knowledge on the key bioactive and nutritional components of hawthorn and emblic leafflower fruits. These results provide important information for research on the mechanism responsible for the health benefits of these fruits.

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The development of new technologies to supplement fossil resources has led to a growing interest in the utilization of alternative routes. Biomass is a rich renewable feedstock for producing fine chemicals, polymers, and a variety of commodities replacing petroleumderived chemicals. Transformation of biomass into diverse valuable chemicals is the key concept of a biorefinery. Catalytic conversion of biomass, which reduces the use of toxic chemicals is one of the important approaches to improve the profitability of biorefineries. Utilization of gold catalysts allows conducting reactions under environmentally-friendly conditions, with a high catalytic activity and selectivity. Gold-catalyzed valorization of several biomass-derived compounds as an alternative approach to the existing technologies was studied in this work. Isomerization of linoleic acid via double bond migration towards biologically active conjugated linoleic acid isomers (CLA) was investigated. The activity and selectivity of various gold catalysts towards cis-9,trans-11-CLA and trans-10,cis-12-CLA were investigated in a semi-batch reactor, showing that the yield of the desired products varied, depending on the catalyst support. The structure sensitivity in the selective oxidation of arabinose was demonstrated using a series of gold catalysts with different Au cluster sizes in a shaker reactor operating in a semibatch mode. The gas-phase selective oxidation of ethanol was studied and the influence of the catalyst support on the catalytic performance was investigated. The selective oxidation of the lignan hydroxymatairesinol (HMR), extracted from the Norway spruce (Picea abies) knots, to the lignan oxomatairesinol (oxoMAT) was extensively investigated. The influence of the reaction conditions and catalyst properties on the yield of oxoMAT was evaluated. In particular, the structure sensitivity of the reaction was demonstrated. The catalyst deactivation and regeneration procedures were studied. The reaction kinetics and mechanism were advanced.

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This thesis is based on computational chemistry studies on lignans, focusing on the naturally occurring lignan hydroxymatairesinol (HMR) (Papers I II) and on TADDOL-like conidendrin-based chiral 1,4-diol ligands (LIGNOLs) (Papers III V). A complete quantum chemical conformational analysis on HMR was previously conducted by Dr. Antti Taskinen. In the works reported in this thesis, HMR was further studied by classical molecular dynamics (MD) simulations in aqueous solution including torsional angle analysis, quantum chemical solvation e ect study by the COnductorlike Screening MOdel (COSMO), and hydrogen bond analysis (Paper I), as well as from a catalytic point of view including protonation and deprotonation studies at di erent levels of theory (Paper II). The computational LIGNOL studies in this thesis constitute a multi-level deterministic structural optimization of the following molecules: 1,1-diphenyl (2Ph), two diastereomers of 1,1,4-triphenyl (3PhR, 3PhS), 1,1,4,4-tetraphenyl (4Ph) and 1,1,4,4-tetramethyl (4Met) 1,4-diol (Paper IV) and a conformational solvation study applying MD and COSMO (Paper V). Furthermore, a computational study on hemiketals in connection with problems in the experimental work by Docent Patrik Eklund's group synthesizing the LIGNOLs based on natural products starting from HMR, is shortly described (Paper III).

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The human body eliminates foreign compounds primarily by metabolizing them to hydrophilic forms to facilitate effective excretion through the kidneys. Cytochrome P450 (CYP) enzymes in the liver and intestine contribute to the metabolism of many drugs. Pharmacokinetic drugdrug interactions occur if the activity of CYPs are inhibited or induced by another drug. Prescribing multiple drugs to the improve effectiveness of therapy or to treat coexisting diseases is a common practice in clinical medicine. Polypharmacy predisposes patients to adverse effects because of the profound unpredictability in CYP enzymatic-mediated drug metabolism. S-ketamine is a phencyclidine derivative which functions as an antagonist of the N-methyl-Daspartate (NMDA) receptor in the central nervous system. It is a unique anaesthetic producing “dissociative anaesthesia” in high doses and analgesia in low doses. Studies with human liver microsomes suggest that ketamine is metabolized primarily via CYP3A4 and CYP2B6 enzymes. In this thesis, in healthy volunteers, randomized and controlled cross-over studies were conducted to investigate the effects of different CYP inducers and inhibitors on the pharmacokinetics and pharmacodynamics of oral and intravenous S-ketamine. The plasma concentrations of ketamine and its metabolite, norketamine, were determined at different timepoints over a 24 hour period. Other pharmacodynamic variables were examined for 12 hours. Results of these studies showed that the inhibition of the CYP3A4 pathway by clarithromycin or grapefruit juice increased the exposure to oral S-ketamine by 2.6- and 3.0-fold. Unexpectedly, CYP3A4 inhibition by itraconazole caused no significant alterations in the plasma concentrations of oral S-ketamine. CYP3A4 induction by St. John´s wort or rifampicin decreased profoundly the concentrations of oral S-ketamine. However, after rifampicin, there were no significant differences in the plasma concentrations of S-ketamine when it was administered intravenously. This demonstrated that rifampicin inhibited the metabolism of Sketamine at the intestinal level. When CYP2B6 was inhibited by ticlopidine, there was a 2.4- fold increase in the exposure of S-ketamine. These studies demonstrated that low dose oral Sketamine is metabolized both via CYP3A4 and CYP2B6 pathways. The concomitant use of drugs that affect CYP3A4 or CYP2B6, during oral S-ketamine treatment, may cause clinically significant drug-drug interactions.

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In order to determine auscultatory and electrocardiographic characteristics of Crioulo horses, one hundred animals ranging between one and twenty-six years of age (21 stallions, nine geldings, 27 pregnant mares e 43 not pregnant mares) were evaluated. The cardiac auscultation was performed during the clinical examination of the cardiovascular system, evaluating frequency, rate, normal and abnormal heart sounds (heart murmurs). The electrocardiographic examination followed the bipolar base-apex derivative system with animals at rest, by using an ECG-PC TEB equipment. The cardiac frequency, heart rate, morphology, duration, wave and complex amplitudes and interval durations were determined. The results were submitted to ANOVA and Tukey tests with an error probability of 5%. The cardiac auscultation revealed presence of functional systolic and diastolic murmur (10.00%) and systolic murmur compatible with tricuspid regurgitation besides normal heart sounds S1 (100.0%), S2 (100.0%), S3 (19.0%) and S4 (34.0%). The cardiac frequency obtained the average of 43.64 bpm, observing significative differences in relation to sexual and age factors and training level. The sinus rhythm was the most frequent (57.00%), followed by sinus tachycardia (38.00%) and sinus arrhythmia (5.00%), being observed rhythm disturbances in 16% of tracings. The P and T waves were observed more frequently in their forms P bifida positive (95.00%) and biphasic T (91.00%), being variable at tracing. There were also observed Q waves in 12.00% of the tracings. Thus, it was concluded that the auscultatory characteristics of Crioulo horses are according to the described in the literature for the species and the sexual factor, category, age factor and training level can influence some electrocardiographic parameters.

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Design of flight control laws, verification of performance predictions, and the implementation of flight simulations are tasks that require a mathematical model of the aircraft dynamics. The dynamical models are characterized by coefficients (aerodynamic derivatives) whose values must be determined from flight tests. This work outlines the use of the Extended Kalman Filter (EKF) in obtaining the aerodynamic derivatives of an aircraft. The EKF shows several advantages over the more traditional least-square method (LS). Among these the most important are: there are no restrictions on linearity or in the form which the parameters appears in the mathematical model describing the system, and it is not required that these parameters be time invariant. The EKF uses the statistical properties of the process and the observation noise, to produce estimates based on the mean square error of the estimates themselves. Differently, the LS minimizes a cost function based on the plant output behavior. Results for the estimation of some longitudinal aerodynamic derivatives from simulated data are presented.