Browsing by master's degree program "Master 's Programme in Materials Research"

Kartiokeilatietokonetomografia eli KKTT on tyypillisimmin käytetty kuvausmodaliteetti kuvantaohjatussa sädehoidossa ja sitä käytetään pääasiassa potilaan asemointiin ja sädehoidon kohdistamiseen. KKTT-kuvantaminen perustuu röntgensäteilyyn ja sen käytön haittapuolena potilas saa ylimääräistä säteilyannosta sekä hoidettavalle alueelle että sitä ympäröiville terveille kudoksille. Eturauhassyöpä on miesten yleisin syöpätyyppi Suomessa ja paikallista eturauhassyöpää voidaan hoitaa esimerkiksi sädehoidolla. Ionisoivan säteilyn käyttö lisää terveiden kudosten syöpäriskiä ja siksi KKTT-kuvantamisen aiheuttaman säteilyannoksen määritys ja optimointi on tärkeää. Tämän työn tarkoituksena on selvittää yhdeksässä suomalaisessa sairaalassa käytettäviä KKTT-kuvantamisen kuvausparametreja ja kuvauskäytäntöjä sekä laskennallisesti määrittää kuvantamisen aiheuttamia potilasannoksia ja optimoinnin vaikutuksia. Laskenta tehdään käyttäen Monte Carlo menetelmään perustuvaa ImpactMC-ohjelmaa, ICRP:n vokselitestikappaletta ja suomalaisten sairaaloiden käyttämiä kuvantamisen parametreja. Tulosten esittämiseen käytetään riskielinten kokonais- ja elinannoksia, isodoosipiirroksia xy- ja xz-tasoissa, riskielinten annostilavuushistogrammeja sekä annosprofiileja xy- ja xz-tasoissa. Tässä työssä lasketut riskielinten elinannokset ovat yhdellä kuvauskerralla noin mGy:n luokkaa ja kokonaissäteilyannokset riippuvat vahvasti kuvausfraktioiden määrästä. Symmetrisen keilan geometriassa säteilyannokset ovat pienempiä kuin epäsymmetrisen keilan geometriassa. Kuvantamisessa käytettävä kuvausalueen pituus, kuvausputken aloituskulma ja kuvausputken kiertosuunta vaikuttavat symmetrisessä geometriassa myös eri riskielimien saamaan säteilyannokseen ja säteilyn jakautumiseen xz-tasossa. Tuloksista havaitaan, että sekä symmetrisen että epäsymmetrisen keilan tapauksissa kuvausparametrien optimointi esimerkiksi putkivirtaa laskemalla pienentää eturauhasen, peräsuolen, reisiluun punaista luuydintä sisältävän osan ja virtsarakon saamaa elinannosta. Kuvausparametrien optimointi pienentää annostasoja myös kaikissa muissa lasketuissa tapauksissa kuten isodoosipiirroksissa ja annosprofiileissa.

Lentoaika-rekyylispektrometria (TOF-ERDA) on materiaalin tutkimusmenetelmä, minkä avulla kyetään selvittämään näytteen alkuainepitoisuudet syvyyden funktiona. Menetelmässä on huomattu esiintyvän systemaattista poikkeamaa teoriasta. Poikkeaman syy on toistaiseksi epäselvä. Tutkielmassa tutkittiin poikkeaman syytä sekä suuruutta. Tutkimiseen käytettiin Helsingin yliopiston kiihdytinlaboratorion 5 MV EPG-10-II-tandemkiihdyttimeen liitettyä TOF-ERDA-laitteistoa. Laitteistolla tutkittiin ilmiön esiintymistä eri hiukkasilla, eri energioilla ja eri näytteillä. Kokeiden tuloksia verrattiin teorian ehdottamiin tuloksiin. Suurimmat poikkeamat kokeiden ja teorian välillä esiintyi pienienergisillä ja keveillä ammusioneilla, kun tutkittiin raskasalkuaineista näytettä. Kokeissa käytettyjen hiukkasten sirontaa TOF-ERDA-laitteiston lentoaikaporteista selvitettiin simuloinneilla. Simulointityökaluna työssä käytettiin SRIM-ohjelmistoa. Simulointien pohjalta hiukkasille laskettiin korjauskertoimet. Korjauskertoimen suuruuden huomattiin olevan riippuvainen hiukkasen energiasta sekä järjestysluvusta. Korjauskertoimista luotiin malli, jonka avulla kyetään arvioimaan ja korjaamaan kokeissa tapahtuvaa sirontaa lentoaikaporteista. Myös varjostumisen vaikutusta tuloksiin tutkittiin. Varjostumista tutkittiin jo olemassa olevan Andersenin mallin avulla. Andersenin mallin mukaan varjostumisen vaikutus tuloksiin on hyvin vähäistä sekä ilmiötä pienentävää, ei ilmiötä selittävää. Huomioitavaa kuitenkin on mallin soveltumattomuus kyseisiin vuorovaikutuksiin, täten varjostumisen vaikutusta ilmiöön ei voida kokonaan poissulkea. Tutkielman tulokset valottavat TOF-ERDA:n systemaattisen poikkeaman syitä. Lentoaikaporttisironnan vaikutus tuloksiin on merkittävä, selittäen noin puolet ilmiöstä. Tulosten pohjalta luotu malli on voimassa vain kyseiselle TOF-ERDA-laitteistolle, sillä sironnan suuruus on riippuvainen lentoaikaporttien materiaalista, paksuuksista sekä laitteiston geometriasta. Kuitenkin mille tahansa TOF-ERDA-laitteistolle on mahdollista luoda vastaava malli, noudattamalla tämän tutkielman prosesseja. Jäljelle jäävän selittämättömän poikkeaman huomattiin olevan myös riippuvainen energiasta sekä järjestysluvuista. Tämä viittaisi jäljelle jäävän poikkeaman aiheutuvan mahdollisesta monikertasironnasta näytteessä, ja tai varjostumisesta, jota Andersenin malli ei kykene huomioimaan.

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating cortical neurons in the brain. Combining TMS with functional magnetic resonance imaging (fMRI) shows the effects of TMS through the changes in brain metabolism. This information is necessary for developing new applications of TMS and for improving the efficacy and safety of the existing treatments. The biggest setback in current TMS–fMRI technology arises from the mechanical forces formed on the transducer as the interplay of the magnetic fields from the MRI and the changing current in the coil, leading to breakage of the transducers and additional safety risks. The objective of this Thesis was to assess and compare the mechanical stresses on multi-locus TMS (mTMS) transducers inside a high-field fMRI bore using finite element modeling, and to build and test transducer options based on the simulation results. For a transducer design for rats, six different coil former materials and three mTMS coil combinations were simulated with two commonly used current waveforms. In addition, the effect of the transducer orientation relative to the magnetic field was modeled with a transducer designed for humans. Our results show that the current pulses ran through the coils produce shock waves on the coil formers, leading to regions of maximum stresses that depend on the time instant. The intensity and location of the maximum stresses depends on the current waveform and coil combination used. Based on the results, 30% glass-fiber filled polyamide was found to be the most durable material. This Thesis provides novel insights for more durable TMS coil designs.

Energy is an essential input for any non-spontaneous mechanism. In biological organisms, the process of producing energy currency, adenosine triphosphate, is called cellular respiration. It is made of three smaller steps, out of which the last one is oxidative phosphorylation that is responsible for the largest production of adenosine triphosphate molecules in the whole process. Oxidative phosphorylation is performed by the electron transport chain made of five protein complexes, named respiratory complex I-V. Complex I is the first and largest protein complex in the electron transport chain, and it is the least understood. Its primary function is to transfer electrons from nicotinamide adenine dinucleotide to ubiquinone, which is coupled to the pumping of four protons across the mitochondrial inner membrane. Although the overall reaction of complex I is understood, the intricate detail of the mechanism is still largely unknown. There is significance in the details because there are numerous point mutations, which have been strongly correlated with neurogenerative diseases, such as Leigh’s syndrome, and aging. Therefore, a more thorough understanding of its mechanism can give insight into potential target drug development. Complex I is made of 14 highly conserved subunits that can be found in most species that use the electron transport chain. They create an L-shape, where seven subunits are embedded in the inner membrane, the membrane domain, and the others are floating in the mitochondrial matrix, the peripheral arm. In mitochondrial complex I, however, there are in addition around 30 accessory subunits. It has been previously thought that the main mechanism is conducted by the 14 subunits that are found in all species. However, in the past couple of years, it has been shown that accessory subunits can play an important role in the mechanism of mitochondrial complex I. The work presented in this thesis uses a multiscale computational approach to study the effect of three mutations, F89A, Y43A and L42A, from an accessory subunit LYRM6 on the function of complex I. Previous experiments demonstrated that the mutations decreased the overall activity of complex I by 76-86 %. The LYRM6 subunit is located at the pivot of the membrane and periplasmic domains. The results of this study show that the point mutations have a long-range effect on the conformations of three loops from three conserved subunits in this region. The shift in the loop dynamics causes a drop in water occupancy. The observed water pathway is tested for the capability of proton transfer. The findings are demonstrated with the help of molecular dynamics and quantum mechanics/molecular mechanics simulations.

Ensuring adequate air quality is integral to healthy living. Since in modern societies the majority of time is spent indoors, understanding indoor air pollution and the means of air purification are of great importance. Adverse health effects are induced by volatile organic compounds (VOC) that originate from everyday activities and our surroundings. Photocatalysis is a radiation-activated chemical transformation that can be used to decompose organic pollutants into harmless constituents. However, existing air purification solutions employing photocatalysis often rely on UV light limiting the use of solar radiation. Titanium dioxide is a popular photocatalyst material, but it requires modification to its electronic properties to respond to visible light. An established approach is to introduce atoms of other dopant elements into the titania lattice. Atomic layer deposition (ALD) is a thin film deposition technique widely studied especially in metal and metal oxide research. Following from the principle of sequential saturation of the surface, control over the size and composition of the film may reach atomic level. Since the chemical configuration of a doped TiO2 film is of utmost importance to successful modification, ALD is an excellent tool to examine suitable photocatalytic TiO2 chemistries. Furthermore, thin solid films of catalytically active material would have a distinguished advantage for deployment in real-life settings over their powderous counterparts. The literature review of this thesis explores the semiconductor photocatalysis with an eye on its suitability to indoor air purification. The motivation is to give the reader a view on the air quality issue, the existing technological solutions and how a thin film photocatalyst could supplement the field. Titanium dioxide doping concepts are introduced to elucidate the rationale behind the experimental efforts. The experimental part describes a development project to deposit visible-light responding photocatalysts. Titanium dioxide thin films co-doped with nitrogen and zinc/fluorine were grown on steel plates. An in-house built reactor system was used to study acetaldehyde degradation under irradiation. Unfortunately, the reactor experienced a malfunction, rendering a large part of the results futile. Moreover, months of valuable time were lost in chasing a mirage of fallacious data. In the end an ALD grown photocatalyst responding to visible light could not be materialized.

In this project, poly(2-methyl-2-oxazoline)-block-poly(2-n-butyl-2-oxazine)-block-poly(2-methyl-2- oxazoline) (PMeOx-b-PnBuOzi-b-PMeOx) and poly(2-methyl-2-oxazoline)-block-poly(2-n-propyl-2- oxazine) (PMeOx-b-PnPrOzi) with block lengths of 35-20-35 and 100-100, respectively, were synthesized. When dispersed in water these thermoresponsive polymers aggregate into micellar aggregates or form hydrogels. Polymers were characterized with 1H-NMR, GPC, and DLS. Age-related macular edema and diabetic macular edema are the most common reasons for blindness in industrialized countries. The triamcinolone acetonide, a corticosteroid used to treat both of these macular edemas, was loaded into the polymeric micelles or hydrogel of synthesized polymers using the thin film method. The loading efficiency for a triblock copolymer ((PMeOx35-b-PnBuOzi20- b-PMeOx35) polymeric micelles was 4 % at the polymer/drug ratio of 10/4 and for a hydrogel (PMeOx100-b-PnPrOzi100) it was 48 % with the same polymer/drug ratio. The properties of the PMeOx100-b-PnPrOzi100 hydrogel formulations with the drug were studied with rheological measurements, DSC, DLS, and GPC of formulations. The formulation showed storage modulus of 3 kPa and the gelation temperature at 16 °C. From the DSC two glass transition temperatures were obtained, Tg1 at around 12 °C and Tg2 at around 74 °C. The particle size distribution of the formulation obtained with DLS showed that there were assumingly micelles or vesicles with a hydrodynamic radius between 20 and 80 nm. The drug release from the hydrogel formulation was studied with the dialysis membrane method and all the drug was released within 24 hours. Both copolymers formed quite unstable formulations with the drug. The results from this study gives information how polyoxazoline- and polyoxazine-based materials can be used to encapsulate and release corticosteroids, such as triamcinolone acetonide. To increase the drug loading capacity and to stabilize formulations, some surfactants for the drug could be tested in the future.

Positron Annihilation Spectroscopy is a powerful tool for defect characterisation, especially vacancies. Various defect properties can be studied, including defect behaviour at low and high temperatures. Despite the technique having its roots in the mid-20th century, there is little research on fundamental positron behaviour at ultralow temperatures. In this thesis, Positron Annihilation Lifetime Spectroscopy and Doppler Broadening Spectroscopy, two sub-methods of the spectroscopy technique, were used to measure positron trap-free Ge in the temperature range of 14 mK-300 K. Since a positron trap-free sample was used, the purpose was not to study defect processes. Instead, the aim of the thesis was to investigate whether any interesting positron processes could be seen at ultralow temperatures in the annihilation data. Previous research in Al has shown no change in either lifetime or Doppler broadening below 77 K. Measuring the positron lifetime in the sample located in a cryostat required designing a special detector setup, as the count rate was greatly reduced due to geometry. To tackle this, lifetime detectors consisting of BaF2 scintillators and quartz-windowed photomultiplier tubes were used. In addition, both analogue and digital signal processing techniques were tested for the lifetime setup, with the digital method proving to be preferable. Doppler Broadening was measured with a high-purity germanium detector connected to a digital gamma spectrometer. The results show a decrease in S-parameter and an increase in W-parameter with decresing temprature, with the rate of change being greatest at ultralow temperatures. This behaviour is concluded to be due to incomplete positron thermalization. The positron lifetime results are more difficult to interpret, as setup challenges resulted in results of questionable accuracy. Still, the trend suggests no change in lifetime over the whole temperature interval, which is in accordance with previous research.

The crystal structure of magnetite (Fe3O4) involves Fe2+ ions in sites with octahedral (Oh) symmetry and Fe2+ and Fe3+ ions in sites with tetrahedral (Td) symmetry. Magnetite exhibits several interesting physical phenomena, such as the Verwey transition, in which the roles of the different Fe sites are an active subject of research. In the X-ray standing wave (XSW) technique, incoming and diffracted X-ray beams interfere inside a crystal, creating a standing wave with the periodicity of the diffracting atomic lattice. The phase of the wave, i.e. whether the nodes are located on the lattice planes or between them, can be adjusted by finely tuning the diffraction angle. Changing the phase in this way makes it possible to selectively vary the contributions of different atoms and absorption types (dipole versus quadrupole) to the measured total absorption spectrum. Iron K-edge absorption spectra in magnetite were studied in the presence of an XSW in an experiment conducted at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. This thesis presents an analysis of the data gathered during the experiment, with the goal of decomposing the experimentally measured pre-edge peak into its constituent components. The methods used in the analysis include principal component analysis and fitting predicted absorption peaks calculated with the Quanty software to the experimental data. The results show the dipole and quadrupole contributions of the tetrahedral sites responding to changes in the phase of the XSW in opposite ways in a manner consistent with theoretical predictions.

Palmitoylation is an important posttranslational modification, which can change the function of proteins by the addition of fatty acids. In this thesis, I studied how palmitoylation affects the behavior of proteins and their interactions with the membranes. I also investigated the molecular mechanism of acetyl-palmitoyl recruitment by DHHC20, an important step in the palmitoyl transfer reaction. To this end, I used atomistic molecular dynamics simulations, which is a common computational method for studying biomolecules. In the first part of the thesis, I present my simulations and free energy calculations that show that palmitoylation enhances the partitioning of cysteines to the membranes and the spontaneous adsorption of amphipathic helices onto the membrane surface. At high levels, membrane cholesterol negatively impacts both of these properties both in the presence and absence of palmitoylation. However, palmitoylation strongly subdues the negative effect of increasing cholesterol. Moreover, palmitoylation helps proteins to maintain their helical conformation upon membrane binding. Overall, palmitoylation appears to be important for membrane interactions and the structural stability of proteins, especially under conditions of high membrane cholesterol. In the second part of my thesis, I investigated how its ligand, acetylpalmitoyl molecules, enters into the binding site of DHHC20. These simulations revealed that a short amphipathic helix at the gate of the ligand binding may play an important role in ligand recruitment and the overall stability of the enzyme. Moreover, I discovered that the protonation state of the cysteine residues that coordinate zinc cofactors is important for the stability of the zinc ions.

A polyoxazine based reversibly crosslinking hydrogel material developed for MEW was modified to increase its resistance to thermal degradation and impart control over its swelling properties. A portion of side chain functionalized Diels-Alder crosslinking moieties was replaced by hydrophobic octyl groups to induce the formation of a dual network hydrogel of equal crosslink density upon swelling. This modification was found to have no negative effects on the processing behavior of the material and was able to produce MEW printed scaffolds with equal stacking accuracy and fiber shape fidelity at processing temperatures 20˚C lower than a fully chemically crosslinked material. The thermal degradation of this dual network crosslinked material was significantly reduced, showing minuscule increases in viscosity when held at processing temperatures for several hours. The swelling of the dual network hydrogel was found to be similar to that of fully chemically crosslinked hydrogels despite consisting of significantly fewer chemical crosslinks, demonstrating another potential avenue of control over this material property. Finally, promising alterations in mechanical properties were observed in the dual-network hydrogel versus chemically crosslinked hydrogels, along with observations of water induced crystallization attributed to the octyl chains.