CHARACTERIZING THE MECHANISM OF QUETIAPINE DISTRIBUTION IN LIPID-CORE NANOCAPSULES PSEUDO-PHASES USING A VALIDATED LC/UV METHOD

Quetiapine is an atypical antipsychotic used to treat schizophrenia. However, despite great interest for its chronic therapeutic use, quetiapine has some important side effects such as weight gain induction. The development of a quetiapine nanocarrier can potentially target the drug into central nervous system, resulting in a reduction of systemic side effects and improved patient treatment. In the present work, a simple liquid chromatography/ultraviolet detection (LC/UV) analytical method was developed and validated for quantification of total quetiapine content in lipid core nanocapsules as well as for determination of incorporation efficiency. An algorithm proposed by Oliveira et al. (2012) was applied to characterize the distribution of quetiapine in the pseudo-phases of the nanocarrier, leading to a better understanding of the quetiapine nanoparticles produced. The analytical methodology developed was specific, linear in the range of 0.5 to 100 µg mL−1 (r2 > 0,99), and accurate and precise (R.S.D < ±5%). The absolute recovery of quetiapine from the nanoparticles was approximately 98% with an incorporation efficiency of approximately 96%. The results indicated that quetiapine was present in a type III distribution according to the algorithm, and was mainly located in the core of the nanoparticle because of its logD in the formulation pH (6.86 ± 0.4).

The Role of Integrins in Enterovirus Infections and in Metastasis of Cancer

Integrins are a family of transmembrane glycoproteins, composed of two different subunits (alpha and beta). Altered expression of integrins in tumor cells contributes to metastasis tendency by influencing on the cells‟ attachment to adjacent cells and their migration. Viral pathogens, including certain enteroviruses, use integrins as receptors. Enteroviruses have also been suggested to be involved in the etiopathogenesis of type 1 diabetes. The study focuses on the role of integrins in the pathogenesis of metastasis to cortical bone and on type 1 diabetes (T1D) and echovirus 1 infection. In the first part of the thesis, the role of different integrins in the initial attachment of MDA-MD-231 breast cancer cells to bovine cortical bone disks was studied. A close correlation between alpha2beta1 and alpha3beta1 integrin receptor expression and the capability of the tumor to attach to bone were observed. In the second part, a possible correlation between susceptibility to enterovirus infections in diabetic children and differences in enterovirus receptor genes, including certain integrins, was investigated. In parallel, virus-specific neutralizing antibodies and diabetic risk alleles were studied. In the diabetic group, an amino acid change was detected in the polio virus receptor and the neutralizing antibody titers against echovirus 30 were lower. However, to obtain statistically sustainable results, a larger number of individuals should be analyzed. Echovirus 1 (EV1) enters cells by attaching to the alpha2I domain of the alpha2beta1 integrin. In the third part EV1 was shown to attach to a chimeric receptor construct of the transferrin receptor and the alpha2I domain and to enter cells through clathrin-mediated endocytosis that is normally not used by the virus. The chimeric receptor was recycled to the plasma membrane, whereas the virus remained in intracellular vesicles. The virus replication cycle was initiated in these cells, suggesting that evolution pressure could possibly cause the virus to evolve to use a different entry mechanism. Moreover, a cDNA microarray analysis of host gene expression during EV1 replication showed that 0.53% of the total genes, including several immediate early genes, were differently expressed.

Photoinhibition of Photosystem II. Kinetics, Photoprotection and Mechanism

Photosystem II (PSII) is susceptible to light-induced damage defined as photoinhibition. In natural conditions, plants are capable of repairing the photoinhibited PSII by on-going degradation and re-synthesis of the D1 reaction centre protein of PSII. Photoinhibition is induced by both visible and ultraviolet light and photoinhibition occurs under all light intensities with the same efficiency per photon. In my thesis work, I studied the reaction kinetics and mechanism of photoinhibition of PSII, as well as photoprotection in leaves of higher plants. Action spectroscopy was used to identify photoreceptors of photoinhibition. I found that the action spectrum of photoinhibition in vivo shows resemblance to the absorption spectra of manganese model compounds of the oxygen evolving complex (OEC) suggesting a role for manganese as a photoreceptor of photoinhibition under UV and visible light. In order to study the protective effect of non-photochemical quenching, the action spectrum was measured from leaves of wild type Arabidopsis thaliana and two mutants impaired in nonphotochemical quenching of chlorophyll a excitations. The findings of action spectroscopy and simulations of chlorophyll-based photoinhibition mechanisms suggested that quenching of antenna excitations protects less efficiently than would be expected if antenna chlorophylls were the only photoreceptors of photoinhibition. The reaction kinetics of prolonged photoinhibition was studied in leaves of Cucurbita maxima and Capsicum annuum. The results indicated that photoinhibitory decrease in both the oxygen evolution activity and ratio of variable to maximum fluorescence follows firstorder kinetics in vivo. The persistence of first-order kinetics suggests that already photoinhibited reaction centres do not protect against photoinhibition and that the mechanism of photoinhibition does not have a reversible intermediate. When Cucurbita maxima leaves were photoinhibited with saturating single-turnover flashes and continuous light, the light response curve of photoinhibition was found to be essentially a straight line with both types of illumination, suggesting that similar photoinhibition mechanisms might function during illumination with continuous light and during illumination with short flashes.

About the kinetics and mechanism of the reactions of 4-(2-pyridylazo)-resorcinol, with Zn2+, Cu2+ and Zn2++Cu2+ equimolar mixtures, in aqueous solutions

The kinetics and mechanism of the reactions between 4(2pyridylazo)-resorcinol and Zn2+, Cu2+ and Zn2++Cu2+ equimolar mixtures were studied. The reactions were performed in aqueous solution (pH = 8.5, borate buffer) and monitored spectrophotometrically at 500 nm using stopped-flow technique. Spectral and kinetic data indicate that the Zn2++Cu2+ equimolar mixture behaves as an unique species and it can be attributed to the interactions of Zn2+ and of Cu2+ with water molecules in the aqueous solution. A mechanism is proposed and the rate constants are calculated.

Parallel-Operating Three-Phase Voltage Source Inverters – Circulating CurrentModeling, Analysis and Mitigation

The maximum realizable power throughput of power electronic converters may be limited or constrained by technical or economical considerations. One solution to this problemis to connect several power converter units in parallel. The parallel connection can be used to increase the current carrying capacity of the overall system beyond the ratings of individual power converter units. Thus, it is possible to use several lower-power converter units, produced in large quantities, as building blocks to construct high-power converters in a modular manner. High-power converters realized by using parallel connection are needed for example in multimegawatt wind power generation systems. Parallel connection of power converter units is also required in emerging applications such as photovoltaic and fuel cell power conversion. The parallel operation of power converter units is not, however, problem free. This is because parallel-operating units are subject to overcurrent stresses, which are caused by unequal load current sharing or currents that flow between the units. Commonly, the term ’circulatingcurrent’ is used to describe both the unequal load current sharing and the currents flowing between the units. Circulating currents, again, are caused by component tolerances and asynchronous operation of the parallel units. Parallel-operating units are also subject to stresses caused by unequal thermal stress distribution. Both of these problemscan, nevertheless, be handled with a proper circulating current control. To design an effective circulating current control system, we need information about circulating current dynamics. The dynamics of the circulating currents can be investigated by developing appropriate mathematical models. In this dissertation, circulating current models aredeveloped for two different types of parallel two-level three-phase inverter configurations. Themodels, which are developed for an arbitrary number of parallel units, provide a framework for analyzing circulating current generation mechanisms and developing circulating current control systems. In addition to developing circulating current models, modulation of parallel inverters is considered. It is illustrated that depending on the parallel inverter configuration and the modulation method applied, common-mode circulating currents may be excited as a consequence of the differential-mode circulating current control. To prevent the common-mode circulating currents that are caused by the modulation, a dual modulator method is introduced. The dual modulator basically consists of two independently operating modulators, the outputs of which eventually constitute the switching commands of the inverter. The two independently operating modulators are referred to as primary and secondary modulators. In its intended usage, the same voltage vector is fed to the primary modulators of each parallel unit, and the inputs of the secondary modulators are obtained from the circulating current controllers. To ensure that voltage commands obtained from the circulating current controllers are realizable, it must be guaranteed that the inverter is not driven into saturation by the primary modulator. The inverter saturation can be prevented by limiting the inputs of the primary and secondary modulators. Because of this, also a limitation algorithm is proposed. The operation of both the proposed dual modulator and the limitation algorithm is verified experimentally.

Permanent Magnet Synchronous Machine for Parallel Hybrid Vehicle

The aim of this thesis is to describe hybrid drive design problems, the advantages and difficulties related to the drive. A review of possible hybrid constructions, benefits of parallel, series and series-parallel hybrids is done. In the thesis analytical and finite element calculations of permanent magnet synchronous machines with embedded magnets were done. The finite element calculations were done using Cedrat’s Flux 2D software. This machine is planned to be used as a motor-generator in a low power parallel hybrid vehicle. The boundary conditions for the design were found from Lucas-TVS Ltd., India. Design Requirements, briefly: • The system DC voltage level is 120 V, which implies Uphase = 49 V (RMS) in a three phase system. • The power output of 10 kW at base speed 1500 rpm (Torque of 65 Nm) is desired. • The maximum outer diameter should not be more than 250 mm, and the maximum core length should not exceed 40 mm. The main difficulties which the author met were the dimensional restrictions. After having designed and analyzed several possible constructions they were compared and the final design selected. Dimensioned and detailed design is performed. Effects of different parameters, such as the number of poles, number of turns and magnetic geometry are discussed. The best modification offers considerable reduction of volume.

Efficiency of pneumatic and horizontal perforated disk meter mechanism in corn no-tillage seeders in soil with different mobilization reports

This work objectified to evaluate the efficiency of two meter mechanism of corn seeds when submitted to different forward speed and soil management system during the non-tillage seeding. It was used a factorial design in randomized blocks. The factors whose effects were examined were related to the seeders with pneumatic and horizontal disk meter mechanisms for the distribution of the seeds, to the set tractor-seeder forward speeds (4.4; 8.0 and 9.8 km h-1), and to the soil management system considering the corn no-tillage seeding over minimum tillage with chisel plow and the no-tillage system for the seeding of oat culture (Avena strigosa Schreb). It was verified that the forward speed didn't influence the initial and final stands of plants but it interfered in the regularity of longitudinal distribution of plants. The smallest speed provided the largest percentile of normal spacing between plants. The pneumatic meter mechanism presented better performance than the horizontal disk perforated in the longitudinal distribution of plants. About corn productivity aspect it's indifferent the recommendation of use for pneumatic and perforated horizontal disk meter mechanism of seeds.

Optimizing Customer Energy Invoice Calculation with Parallel Computation

Diplomityön tarkoituksena on optimoida asiakkaiden sähkölaskun laskeminen hajautetun laskennan avulla. Älykkäiden etäluettavien energiamittareiden tullessa jokaiseen kotitalouteen, energiayhtiöt velvoitetaan laskemaan asiakkaiden sähkölaskut tuntiperusteiseen mittaustietoon perustuen. Kasvava tiedonmäärä lisää myös tarvittavien laskutehtävien määrää. Työssä arvioidaan vaihtoehtoja hajautetun laskennan toteuttamiseksi ja luodaan tarkempi katsaus pilvilaskennan mahdollisuuksiin. Lisäksi ajettiin simulaatioita, joiden avulla arvioitiin rinnakkaislaskennan ja peräkkäislaskennan eroja. Sähkölaskujen oikeinlaskemisen tueksi kehitettiin mittauspuu-algoritmi.

Advanced ceramics: evaluation of the mechanism of stock removal and ground surface quality

The aim of this work is to evaluate the mechanism of stock removal and the ground surface quality of advanced ceramics machined by a surface grinding process using diamond grinding wheels. The analysis of the grinding performance was done regarding the cutting surface wear behavior of the grinding wheel for ceramic workpieces. The ground surface was evaluated using Scanning Electron Microscopy (SEM). As a result it can be said that the mechanism of material removal in the grinding of ceramic is largely one of brittle fracture. The increase of the h max can reduce the tangential force required by the process. Although, it results in an increase in the surface damage, reducing the mechanical properties of the ground component.

Inverse convection problem of simultaneous estimation of two boundary heat fluxes in parallel plate channels

This paper deals with the use of the conjugate gradient method of function estimation for the simultaneous identification of two unknown boundary heat fluxes in parallel plate channels. The fluid flow is assumed to be laminar and hydrodynamically developed. Temperature measurements taken inside the channel are used in the inverse analysis. The accuracy of the present solution approach is examined by using simulated measurements containing random errors, for strict cases involving functional forms with discontinuities and sharp-corners for the unknown functions. Three different types of inverse problems are addressed in the paper, involving the estimation of: (i) Spatially dependent heat fluxes; (ii) Time-dependent heat fluxes; and (iii) Time and spatially dependent heat fluxes.

Investigation on diamond turning of silicon crystal - generation mechanism of surface cut with worn tool

This paper discusses the effect of tool wear on surface finish in single-point diamond turning of single crystal silicon. The morphology and topography of the machined surface clearly show the type of cutting edge wear reproduced onto the cutting grooves. Scanning electron microscopy is used in order to correlate the cutting edge damage and microtopography features observed through atomic force microscopy. The possible wear mechanisms affecting tool performance and surface generation during cutting are also discussed. The zero degree rake angle single point diamond tool presented small nicks on the cutting edge. The negative rake angle tools presented more a type of crater wear on the rake face. No wear was detected on flank face of the diamond tools.

Numerical Simulation of the Cavitation in the Hydrodynamic Lubrication of Journal Bearings: a Parallel Algorithm

In this paper we present an algorithm for the numerical simulation of the cavitation in the hydrodynamic lubrication of journal bearings. Despite the fact that this physical process is usually modelled as a free boundary problem, we adopted the equivalent variational inequality formulation. We propose a two-level iterative algorithm, where the outer iteration is associated to the penalty method, used to transform the variational inequality into a variational equation, and the inner iteration is associated to the conjugate gradient method, used to solve the linear system generated by applying the finite element method to the variational equation. This inner part was implemented using the element by element strategy, which is easily parallelized. We analyse the behavior of two physical parameters and discuss some numerical results. Also, we analyse some results related to the performance of a parallel implementation of the algorithm.

Seismic motion simulation based on Cassino Parallel Manipulator

In this paper we present a study of feasibility by using Cassino Parallel Manipulator (CaPaMan) as an earthquake simulator. We propose a suitable formulation to simulate the frequency, amplitude and acceleration magnitude of seismic motion by means of the movable platform motion by giving a suitable input motion. In this paper we have reported numerical simulations that simulate the three principal earthquake types for a seismic motion: one at the epicenter (having a vertical motion), another far from the epicenter (with the motion on a horizontal plane), and a combined general motion (with a vertical and horizontal motion).

Ultrasuodatusmembraanin modifiointi entsyymeillä suodatusominaisuuksien parantamiseksi

Tämän diplomityön tarkoituksena oli kiinnittää lakkaasientsyymi polyeetterisulfonimembraaniin suodatusominaisuuksien parantamiseksi. Lakkaasientsyymin tiedetään pilkkovan ligniiniä ja kiinnittämällä lakkaasientsyymi membraaniin tavoiteltiin ligniinin aiheuttaman membraanin likaantumisen vähentämistä. Tällöin vältyttäisiin lisäksi erilliseltä esikäsittely vaiheelta ja voitaisiin saada puhtaampi lopputuote. Lakkaasientsyymivalmisteena tutkimuksessa käytettiin Novozym® 51003 ja ristisilloittajana käytettiin glutaarialdehydiä. Vapaan ja kiinnitetyn lakkaasientsyymin aktiivisuuden määritettiin 2,2-atso-bis(3- etyylibentsotiatsolyyli-6-sulfonihappo):n avulla. Lakkaasin kiinnittymistä membraaniin tutkittiin ATR-FTIR spektroskoopilla kiinnittymisen varmentamiseksi. Lakkaasi modifioituja membraaneja testattiin koivu-uute suodatuksella ja adsorptio kokeella. Lakkaasientsyymi saatiin kiinnitettyä membraaniin ristisilloittajan avulla, mutta lakkaasilla modifioitujen membraanien vesivuot laskivat noin puoleen alkuperäisestä. Koivu-uuteen suodatuksissa modifioidusta membraanista ei saatu permeaattia lävitse, mutta adsorptiokokeen tulosten perusteella voidaan todeta lakkaasientsyymin pilkkoneen ligniiniä. Kiinnitetyn lakkaasin aktiivisuus vaihteli rinnakkaisten määritysten välillä, minkä vuoksi lakkaasin kiinnitysmekanismin lisätutkiminen olisi tarpeen luotettavimpien tulosten saamiseksi.

Energy-efficient control strategies for variable speed driven parallel pumping systems based on pump operation point monitoring with frequency converters

The pumping processes requiring wide range of flow are often equipped with parallelconnected centrifugal pumps. In parallel pumping systems, the use of variable speed control allows that the required output for the process can be delivered with a varying number of operated pump units and selected rotational speed references. However, the optimization of the parallel-connected rotational speed controlled pump units often requires adaptive modelling of both parallel pump characteristics and the surrounding system in varying operation conditions. The available information required for the system modelling in typical parallel pumping applications such as waste water treatment and various cooling and water delivery pumping tasks can be limited, and the lack of real-time operation point monitoring often sets limits for accurate energy efficiency optimization. Hence, alternatives for easily implementable control strategies which can be adopted with minimum system data are necessary. This doctoral thesis concentrates on the methods that allow the energy efficient use of variable speed controlled parallel pumps in system scenarios in which the parallel pump units consist of a centrifugal pump, an electric motor, and a frequency converter. Firstly, the suitable operation conditions for variable speed controlled parallel pumps are studied. Secondly, methods for determining the output of each parallel pump unit using characteristic curve-based operation point estimation with frequency converter are discussed. Thirdly, the implementation of the control strategy based on real-time pump operation point estimation and sub-optimization of each parallel pump unit is studied. The findings of the thesis support the idea that the energy efficiency of the pumping can be increased without the installation of new, more efficient components in the systems by simply adopting suitable control strategies. An easily implementable and adaptive control strategy for variable speed controlled parallel pumping systems can be created by utilizing the pump operation point estimation available in modern frequency converters. Hence, additional real-time flow metering, start-up measurements, and detailed system model are unnecessary, and the pumping task can be fulfilled by determining a speed reference for each parallel-pump unit which suggests the energy efficient operation of the pumping system.