Vapaa-ajan vieton luonnonvarojen kulutus

This thesis studies the use of natural resources for leisure time activities. The method used is Material Input per Service Unit (MIPS method). Leisure time has an increasing effect on the material flows of households, and that way has a bigger pressure on the environment. The most popular way of spending spare time in Finland is to watch TV and to listen to music or radio. Regardless of these, this thesis takes a closer look at boating, playing a musical instrument and visiting a theatre and tries to quantify their material flows. MIPS calculations of this thesis are case-studies and do not tell the whole truth about the hobbies. The aim was to have an overview about the magnitude of the activities. In the boating calculations, inside the system boundaries there are the boat itself, transport of the boat, outboard motor, gasoline consumption of the outboard motor, travelling to and from the harbour, and the harbour infrastructure. Calculations of playing a music instrument consider the instrument itself, music school and its maintenance, and travelling to the school. In the case of theatre the included things are theatre house and its maintenance, decor and costumes of the plays, transport of the decor, and travelling of the audience. The results of this thesis suggest that the biggest material flow of boating comes from travelling to and from the harbour and from the harbour infrastructure. The gasoline consumption of the outboard motor also makes a difference. One hour of boating with a rowing boat consumes 1 kg of abiotic materials. Boating with an outboard motorboat consumes astonishing 113 kg of abiotic resources. Visiting a music lesson for one hour consumes 9 kg of abiotic resources when travelling there by bus. One hour in a theatre play consumes 17 kg of abiotic materials when travelling by bus. Transport has a significant role on the resource consumption of leisure time activities.

Suomen maatalouden tuottamat kasvihuonekaasujen päästöt eri politiikkaskenaarioissa

Climate change is the single biggest environmental problem in the world at the moment. Although the effects are still not fully understood and there is considerable amount of uncertainty, many na-tions have decided to mitigate the change. On the societal level, a planner who tries to find an eco-nomically optimal solution to an environmental pollution problem seeks to reduce pollution from the sources where reductions are most cost-effective. This study aims to find out how effective the instruments of the agricultural policy are in the case of climate change mitigation in Finland. The theoretical base of this study is the neoclassical economic theory that is based on the assumption of a rational economic agent who maximizes his own utility. This theoretical base has been widened towards the direction clearly essential to the matter: the theory of environmental eco-nomics. Deeply relevant to this problem and central in the theory of environmental economics are the concepts of externalities and public goods. What are also relevant are the problems of global pollution and non-point-source pollution. Econometric modelling was the method that was applied to this study. The Finnish part of the AGMEMOD-model, covering the whole EU, was used for the estimation of the development of pollution. This model is a seemingly recursive, partially dynamic partial-equilibrium model that was constructed to predict the development of Finnish agricultural production of the most important products. For the study, I personally updated the model and also widened its scope in some relevant matters. Also, I devised a table that can calculate the emissions of greenhouse gases according to the rules set by the IPCC. With the model I investigated five alternative scenarios in comparison to the base-line scenario of Agenda 2000 agricultural policy. The alternative scenarios were: 1) the CAP reform of 2003, 2) free trade on agricultural commodities, 3) technological change, 4) banning the cultivation of organic soils and 5) the combination of the last three scenarios as the maximal achievement in reduction. The maximal achievement in the alternative scenario 5 was 1/3 of the level achieved on the base-line scenario. CAP reform caused only a minor reduction when com-pared to the base-line scenario. Instead, the free trade scenario and the scenario of technological change alone caused a significant reduction. The biggest single reduction was achieved by banning the cultivation of organic land. However, this was also the most questionable scenario to be real-ized, the reasons for this are further elaborated in the paper. The maximal reduction that can be achieved in the Finnish agricultural sector is about 11 % of the emission reduction that is needed to comply with the Kyoto protocol.

Urban energy fluxes in Helsinki and their high frequency spectral corrections

Inadvertent climate modification has led to an increase in urban temperatures compared to the surrounding rural area. The main reason for the temperature rise is the altered energy portioning of input net radiation to heat storage and sensible and latent heat fluxes in addition to the anthropogenic heat flux. The heat storage flux and anthropogenic heat flux have not yet been determined for Helsinki and they are not directly measurable. To the contrary, turbulent fluxes of sensible and latent heat in addition to net radiation can be measured, and the anthropogenic heat flux together with the heat storage flux can be solved as a residual. As a result, all inaccuracies in the determination of the energy balance components propagate to the residual term and special attention must be paid to the accurate determination of the components. One cause of error in the turbulent fluxes is the fluctuation attenuation at high frequencies which can be accounted for by high frequency spectral corrections. The aim of this study is twofold: to assess the relevance of high frequency corrections to water vapor fluxes and to assess the temporal variation of the energy fluxes. Turbulent fluxes of sensible and latent heat have been measured at SMEAR III station, Helsinki, since December 2005 using the eddy covariance technique. In addition, net radiation measurements have been ongoing since July 2007. The used calculation methods in this study consist of widely accepted eddy covariance data post processing methods in addition to Fourier and wavelet analysis. The high frequency spectral correction using the traditional transfer function method is highly dependent on relative humidity and has an 11% effect on the latent heat flux. This method is based on an assumption of spectral similarity which is shown not to be valid. A new correction method using wavelet analysis is thus initialized and it seems to account for the high frequency variation deficit. Anyhow, the resulting wavelet correction remains minimal in contrast to the traditional transfer function correction. The energy fluxes exhibit a behavior characteristic for urban environments: the energy input is channeled to sensible heat as latent heat flux is restricted by water availability. The monthly mean residual of the energy balance ranges from 30 Wm-2 in summer to -35 Wm-2 in winter meaning a heat storage to the ground during summer. Furthermore, the anthropogenic heat flux is approximated to be 50 Wm-2 during winter when residential heating is important.

Feasibility of assimilating ASCAT surface winds into a Limited Area Model

Sea-surface wind observations of previous generation scatterometers have been successfully assimilated into Numerical Weather Prediction (NWP) models. Impact studies conducted with these assimilation implementations have shown a distinct improvement to model analysis and forecast accuracies. The Advanced Scatterometer (ASCAT), flown on Metop-A, offers an improved sea-surface wind accuracy and better data coverage when compared to the previous generation scatterometers. Five individual case studies are carried out. The effect of including ASCAT data into High Resolution Limited Area Model (HIRLAM) assimilation system (4D-Var) is tested to be neutral-positive for situations with general flow direction from the Atlantic Ocean. For northerly flow regimes the effect is negative. This is later discussed to be caused by problems involving modeling northern flows, and also due to the lack of a suitable verification method. Suggestions and an example of an improved verification method is presented later on. A closer examination of a polar low evolution is also shown. It is found that the ASCAT assimilation scheme improves forecast of the initial evolution of the polar low, but the model advects the strong low pressure centre too fast eastward. Finally, the flaws of the implementation are found small and implementing the ASCAT assimilation scheme into the operational HIRLAM suite is feasible, but longer time period validation is still required.

Noncommutative Gravitation as a Gauge Theory of Twisted Poincaré Symmetry

Gravitaation kvanttiteorian muotoilu on ollut teoreettisten fyysikkojen tavoitteena kvanttimekaniikan synnystä lähtien. Kvanttimekaniikan soveltaminen korkean energian ilmiöihin yleisen suhteellisuusteorian viitekehyksessä johtaa aika-avaruuden koordinaattien operatiiviseen ei-kommutoivuuteen. Ei-kommutoivia aika-avaruuden geometrioita tavataan myös avointen säikeiden säieteorioiden tietyillä matalan energian rajoilla. Ei-kommutoivan aika-avaruuden gravitaatioteoria voisi olla yhteensopiva kvanttimekaniikan kanssa ja se voisi mahdollistaa erittäin lyhyiden etäisyyksien ja korkeiden energioiden prosessien ei-lokaaliksi uskotun fysiikan kuvauksen, sekä tuottaa yleisen suhteellisuusteorian kanssa yhtenevän teorian pitkillä etäisyyksillä. Tässä työssä tarkastelen gravitaatiota Poincarén symmetrian mittakenttäteoriana ja pyrin yleistämään tämän näkemyksen ei-kommutoiviin aika-avaruuksiin. Ensin esittelen Poincarén symmetrian keskeisen roolin relativistisessa fysiikassa ja sen kuinka klassinen gravitaatioteoria johdetaan Poincarén symmetrian mittakenttäteoriana kommutoivassa aika-avaruudessa. Jatkan esittelemällä ei-kommutoivan aika-avaruuden ja kvanttikenttäteorian muotoilun ei-kommutoivassa aika-avaruudessa. Mittasymmetrioiden lokaalin luonteen vuoksi tarkastelen huolellisesti mittakenttäteorioiden muotoilua ei-kommutoivassa aika-avaruudessa. Erityistä huomiota kiinnitetään näiden teorioiden vääristyneeseen Poincarén symmetriaan, joka on ei-kommutoivan aika-avaruuden omaama uudentyyppinen kvanttisymmetria. Seuraavaksi tarkastelen ei-kommutoivan gravitaatioteorian muotoilun ongelmia ja niihin kirjallisuudessa esitettyjä ratkaisuehdotuksia. Selitän kuinka kaikissa tähänastisissa lähestymistavoissa epäonnistutaan muotoilla kovarianssi yleisten koordinaattimunnosten suhteen, joka on yleisen suhteellisuusteorian kulmakivi. Lopuksi tutkin mahdollisuutta yleistää vääristynyt Poincarén symmetria lokaaliksi mittasymmetriaksi --- gravitaation ei-kommutoivan mittakenttäteorian saavuttamisen toivossa. Osoitan, että tällaista yleistystä ei voida saavuttaa vääristämällä Poincarén symmetriaa kovariantilla twist-elementillä. Näin ollen ei-kommutoivan gravitaation ja vääristyneen Poincarén symmetrian tutkimuksessa tulee jatkossa keskittyä muihin lähestymistapoihin.

A Critical Assesment of Occluded Fronts

The aim of this work was the assessment about the structure and use of the conceptual model of occlusion in operational weather forecasting. In the beginning a survey has been made about the conceptual model of occlusion as introduced to operational forecasters in the Finnish Meteorological Institute (FMI). In the same context an overview has been performed about the use of the conceptual model in modern operational weather forecasting, especially in connection with the widespread use of numerical forecasts. In order to evaluate the features of the occlusions in operational weather forecasting, all the occlusion processes occurring during year 2003 over Europe and Northern Atlantic area have been investigated using the conceptual model of occlusion and the methods suggested in the FMI. The investigation has yielded a classification of the occluded cyclones on the basis of the extent the conceptual model has fitted the description of the observed thermal structure. The seasonal and geographical distribution of the classes has been inspected. Some relevant cases belonging to different classes have been collected and analyzed in detail: in this deeper investigation tools and techniques, which are not routinely used in operational weather forecasting, have been adopted. Both the statistical investigation of the occluded cyclones during year 2003 and the case studies have revealed that the traditional classification of the types of the occlusion on the basis of the thermal structure doesn t take into account the bigger variety of occlusion structures which can be observed. Moreover the conceptual model of occlusion has turned out to be often inadequate in describing well developed cyclones. A deep and constructive revision of the conceptual model of occlusion is therefore suggested in light of the result obtained in this work. The revision should take into account both the progresses which are being made in building a theoretical footing for the occlusion process and the recent tools and meteorological quantities which are nowadays available.

The Spin-Statistics Relation and Noncommutative Quantum Field Theory

The efforts of combining quantum theory with general relativity have been great and marked by several successes. One field where progress has lately been made is the study of noncommutative quantum field theories that arise as a low energy limit in certain string theories. The idea of noncommutativity comes naturally when combining these two extremes and has profound implications on results widely accepted in traditional, commutative, theories. In this work I review the status of one of the most important connections in physics, the spin-statistics relation. The relation is deeply ingrained in our reality in that it gives us the structure for the periodic table and is of crucial importance for the stability of all matter. The dramatic effects of noncommutativity of space-time coordinates, mainly the loss of Lorentz invariance, call the spin-statistics relation into question. The spin-statistics theorem is first presented in its traditional setting, giving a clarifying proof starting from minimal requirements. Next the notion of noncommutativity is introduced and its implications studied. The discussion is essentially based on twisted Poincaré symmetry, the space-time symmetry of noncommutative quantum field theory. The controversial issue of microcausality in noncommutative quantum field theory is settled by showing for the first time that the light wedge microcausality condition is compatible with the twisted Poincaré symmetry. The spin-statistics relation is considered both from the point of view of braided statistics, and in the traditional Lagrangian formulation of Pauli, with the conclusion that Pauli's age-old theorem stands even this test so dramatic for the whole structure of space-time.

Quality of ALICE SSD modules revealed by electrical tests

ALICE (A Large Ion Collider Experiment) is an experiment at CERN (European Organization for Nuclear Research), where a heavy-ion detector is dedicated to exploit the unique physics potential of nucleus-nucleus interactions at LHC (Large Hadron Collider) energies. In a part of that project, 716 so-called type V4 modules were assembles in Detector Laboratory of Helsinki Institute of Physics during the years 2004 - 2006. Altogether over a million detector strips has made this project the most massive particle detector project in the science history of Finland. One ALICE SSD module consists of a double-sided silicon sensor, two hybrids containing 12 HAL25 front end readout chips and some passive components, such has resistors and capacitors. The components are connected together by TAB (Tape Automated Bonding) microcables. The components of the modules were tested in every assembly phase with comparable electrical tests to ensure the reliable functioning of the detectors and to plot the possible problems. The components were accepted or rejected by the limits confirmed by ALICE collaboration. This study is concentrating on the test results of framed chips, hybrids and modules. The total yield of the framed chips is 90.8%, hybrids 96.1% and modules 86.2%. The individual test results have been investigated in the light of the known error sources that appeared during the project. After solving the problems appearing during the learning-curve of the project, the material problems, such as defected chip cables and sensors, seemed to induce the most of the assembly rejections. The problems were typically seen in tests as too many individual channel failures. Instead, the bonding failures rarely caused the rejections of any component. One sensor type among three different sensor manufacturers has proven to have lower quality than the others. The sensors of this manufacturer are very noisy and their depletion voltage are usually outside of the specification given to the manufacturers. Reaching 95% assembling yield during the module production demonstrates that the assembly process has been highly successful.

A computational study of Compton profiles of water - methanol solutions

The molecular level structure of mixtures of water and alcohols is very complicated and has been under intense research in the recent past. Both experimental and computational methods have been used in the studies. One method for studying the intra- and intermolecular bindings in the mixtures is the use of the so called difference Compton profiles, which are a way to obtain information about changes in the electron wave functions. In the process of Compton scattering a photon scatters inelastically from an electron. The Compton profile that is obtained from the electron wave functions is directly proportional to the probability of photon scattering at a given energy to a given solid angle. In this work we develop a method to compute Compton profiles numerically for mixtures of liquids. In order to obtain the electronic wave functions necessary to calculate the Compton profiles we need some statistical information about atomic coordinates. Acquiring this using ab-initio molecular dynamics is beyond our computational capabilities and therefore we use classical molecular dynamics to model the movement of atoms in the mixture. We discuss the validity of the chosen method in view of the results obtained from the simulations. There are some difficulties in using classical molecular dynamics for the quantum mechanical calculations, but these can possibly be overcome by parameter tuning. According to the calculations clear differences can be seen in the Compton profiles of different mixtures. This prediction needs to be tested in experiments in order to find out whether the approximations made are valid.

Suomen maankuoren kivilajikoostumuksen tulkinta seismisistä aineistoista

Aim of this study is to investigate composition of the crust in Finland using seismic wide-angle velocity models and laboratory measurements on P- and S-wave velocities of different rock types. The velocities adopted from wide-angle velocity models were compared with laboratory velocities of different rock types corrected for the crustal PT conditions in the study area. The wide-angle velocity models indicate that the P-wave velocity does not only increase step-wise at boundaries of major crustal layers, but there is also gradual increase of velocity within the layers. On the other hand, the laboratory measurements of velocities indicate that no single rock type is able to provide the gradual downward increasing trends. Thus, there must be gradual vertical changes in rock composition. The downward increase of velocities indicates that the composition of the crust becomes gradually more mafic with increasing depth. Even though single rock types cannot simulate the wide-angle model velocities, it can be done with a mixture of rock types. There are a large number of rock type mixtures giving the correct P-wave velocities. Therefore, the inverse solution of rock types and their proportions from velocities is a non-unique problem if only P-wave velocities is available. Amount of the possible rock type mixtures can be limitted using S-wave velocities, reflection seismic results and other geological and geophysical results of the study area. Crustal model FINMIX-2 is presented in this study and it suggest that the crustal velocity profiles can be simulated with rock type mixtures, where the upper crust consists of felsic gneisses and granitic-granodioritic rocks with a minor contribution of quartzite, amphibolite and diabase. In the middle crust the amphibolite proportion increases. The lower crust consists of tonalitic gneiss, mafic garnet granulite, hornblendite, pyroxenite and minor mafic eclogite. This composition model is in agreement with deep crustal kimberlite-hosted xenolith data in eastern Finland and reflectivity of the FIRE (Finnish Reflection Experiment). According to FINMIX-2 model the Moho is deeper and the crustal composition is a more mafic than an average global continental model would suggest. Composition models of southern Finland are quite similar than FINMIX-2 model. However, there are minor differencies between the models, which indicates areal differences of composition. Models of northern Finland shows that the crustal thickness is smaller than southern Finland and composition of the upper crust is different. Density profiles calculated from the lithological models suggest that there is practically no density contrast at Moho in areas of the high-velocity lower crust. This implies that crustal thickness in the central Fennoscandian Shield may have been controlled by the densities of the lower crustal and upper mantle rocks.

Identification of Isoflavonoid Metabolites in Humans

Epidemiological studies have associated high soy intake with a lowered risk for certain hormone-dependent diseases, such as breast and prostate cancers, osteoporosis, and cardiovascular disease. Soy is a rich source of isoflavones, diphenolic plant compounds that have been shown to possess several biological activities. Soy is not part of the traditional Western diet, but many dietary supplements are commercially available in order to provide the proposed beneficial health effects of isoflavones without changing the original diet. These supplements are usually manufactured from extracts of soy or red clover, which is another important source of isoflavones. However, until recently, detailed studies of the metabolism of these compounds in humans have been lacking. The aim of this study was to identify urinary metabolites of isoflavones originating from soy or red clover using gas chromatography - mass spectrometry (GC-MS). To examine metabolism, soy and red clover supplementation studies with human volunteers were carried out. In addition, the metabolism of isoflavones was investigated in vitro by identification of metabolites formed during a 24-h fermentation of pure isoflavones with a human fecal inoculum. Qualitative methods for identification and analysis of isoflavone metabolites in urine and fecal fermentation samples by GC-MS were developed. Moreover, a detailed investigation of fragmentation of isoflavonoids in electron ionization mass spectrometry (EIMS) was carried out by means of synthetic reference compounds and deuterated trimethylsilyl derivatives. After isoflavone supplementation, 18 new metabolites of isoflavones were identified in human urine samples. The most abundant urinary metabolites of soy isoflavones daidzein, genistein, and glycitein were found to be the reduced metabolites, i.e. analogous isoflavanones, a-methyldeoxybenzoins, and isoflavans. Metabolites having additional hydroxyl and/or methoxy substituents, or their reduced analogs, were also identified. The main metabolites of red clover isoflavones formononetin and biochanin A were identified as daidzein and genistein. In addition, reduced and hydroxylated metabolites of formononetin and biochanin A were identified; however, they occurred at much lower levels in urine samples than daidzein or genistein or their reduced metabolites. The results of this study show that the metabolism of isoflavones is diverse. More studies are needed to determine whether the new isoflavonoid metabolites identified here have biological activities that contribute to the proposed beneficial effects of isoflavones on human health. Another task is to develop validated quantitative methods to determine the actual levels of isoflavones and their metabolites in biological matrices in order to assess the role of isoflavones in prevention of chronic diseases.

Enzyme molecular choreography : studies on soluble inorganic pyrophosphatases

Inorganic pyrophosphatases (PPases, EC 3.6.1.1) hydrolyse pyrophosphate in a reaction that provides the thermodynamic 'push' for many reactions in the cell, including DNA and protein synthesis. Soluble PPases can be classified into two families that differ completely in both sequence and structure. While Family I PPases are found in all kingdoms, family II PPases occur only in certain prokaryotes. The enzyme from baker's yeast (Saccharomyces cerevisiae) is very well characterised both kinetically and structurally, but the exact mechanism has remained elusive. The enzyme uses divalent cations as cofactors; in vivo the metal is magnesium. Two metals are permanently bound to the enzyme, while two come with the substrate. The reaction cycle involves the activation of the nucleophilic oxygen and allows different pathways for product release. In this thesis I have solved the crystal structures of wild type yeast PPase and seven active site variants in the presence of the native cofactor magnesium. These structures explain the effects of the mutations and have allowed me to describe each intermediate along the catalytic pathway with a structure. Although establishing the ʻchoreographyʼ of the heavy atoms is an important step in understanding the mechanism, hydrogen atoms are crucial for the mechanism. The most unambiguous method to determine the positions of these hydrogen atoms is neutron crystallography. In order to determine the neutron structure of yeast PPase I perdeuterated the enzyme and grew large crystals of it. Since the crystals were not stable at ambient temperature, a cooling device was developed to allow neutron data collection. In order to investigate the structural changes during the reaction in real time by time-resolved crystallography a photolysable substrate precursor is needed. I synthesised a candidate molecule and characterised its photolysis kinetics, but unfortunately it is hydrolysed by both yeast and Thermotoga maritima PPases. The mechanism of Family II PPases is subtly different from Family I. The native metal cofactor is manganese instead of magnesium, but the metal activation is more complex because the metal ions that arrive with the substrate are magnesium different from those permanently bound to the enzyme. I determined the crystal structures of wild type Bacillus subtilis PPase with the inhibitor imidodiphosphate and an inactive H98Q variant with the substrate pyrophosphate. These structures revealed a new trimetal site that activates the nucleophile. I also determined that the metal ion sites were partially occupied by manganese and iron using anomalous X- ray scattering.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

NMR Spectroscopy of Multi-domain Proteins : Immunoglobulin-like Domains of Human Filamin A

Proteins are complex biomacromolecules playing fundamental roles in the physiological processes of all living organisms. They function as structural units, enzymes, transporters, process regulators, and signal transducers. Defects in protein functions often derive from genetic mutations altering the protein structure, and impairment of essential protein functions manifests itself as pathological conditions. Proteins operate through interactions, and all protein functions depend on protein structure. In order to understand biological mechanisms at the molecular level, one has to know the structures of the proteins involved. This thesis covers structural and functional characterization of human filamins. Filamins are actin-binding and -bundling proteins that have numerous interaction partners. In addition to their actin-organizing functions, filamins are also known to have roles in cell adhesion and locomotion, and to participate in the logistics of cell membrane receptors, and in the coordination of intracellular signaling pathways. Filamin mutations in humans induce severe pathological conditions affecting the brain, bones, limbs, and the cardiovascular system. Filamins are large modular proteins composed of an N-terminal actin-binding domain and 24 consecutive immunoglobulin-like domains (IgFLNs). Nuclear magnetic resonance (NMR) spectroscopy is a versatile method of gaining insight into protein structure, dynamics and interactions. NMR spectroscopy was employed in this thesis to study the atomic structure and interaction mechanisms of C-terminal IgFLNs, which are known to house the majority of the filamin interaction sites. The structures of IgFLN single-domains 17 and 23 and IgFLN domain pairs 16-17 and 18-19 were determined using NMR spectroscopy. The structures of domain pairs 16 17 and 18 19 both revealed novel domain domain interaction modes of IgFLNs. NMR titrations were employed to characterize the interactions of filamins with glycoprotein Ibα, FilGAP, integrin β7 and dopamine receptors. Domain packing of IgFLN domain sextet 16 21 was further characterized using residual dipolar couplings and NMR relaxation analysis. This thesis demonstrates the versatility and potential of NMR spectroscopy in structural and functional studies of multi-domain proteins.

Syntheses and Self-Assembling Characteristics of Amphiphilic Star Diblock Copolymers

Uusien polymeeripohjaisten teknologioiden ja materiaalien myötä räätälöityjen polymeerien tarve on kasvanut. Viime vuosituhannen lopussa kehitetyt kontrolloidut polymerointimenetelmät ovat avanneet uusia mahdollisuuksia paitsi monimutkaisten polymeerien synteesiin, myös itsejärjestyvyyteen perustuvien funktionaalisten nanorakenteiden suunnitteluun ja valmistukseen. Nämä voivat jäljitellä luonnossa esiintyviä rakenteita, joita muodostavat esimerkiksi lipidit ja proteiinit. Itsejärjestyvät molekyylit ovat usein amfifiilisiä eli ne koostuvat hydrofiilisistä ja hydrofobisista osista ja polymeereissä nämä osat voivat olla omina lohkoinaan, jolloin puhutaan amfifiilisistä lohko- tai blokkikopolymeereistä. Riippuen järjestyneiden rakenteiden koostumuksesta ja muodosta, amfifiilisiä blokkikopolymeerejä on tutkittu tai jo käytetty nanoteknologiassa, elastomeereissä, voiteluaineissa, pinta-aktiivisina aineina, lääkkeenannostelussa, maaleissa, sekä elektroniikka-, kosmetiikka- ja elintarviketeollisuudessa. Tavallisimmin käytetyt amfifiiliset blokkikopolymeerit ovat olleet lineaarisia, mutta viime aikoina tutkimus on suuntautunut kohti monimutkaisempia rakenteita. Tällaisia ovat esimerkiksi tähtipolymeerit. Tähtimäisissä polymeereissä miselleille tyypillinen ydin-kuori-rakenne säilyy hyvin alhaisissakin polymeerikonsentraatioissa, koska polymeeriketjut ovat kiinni toisissaan yhdessä pisteessä. Siten ne ovat erityisen kiinnostavia tutkimuskohteita erilaisten hydrofobisten orgaanisten yhdisteiden sitomiseksi ja vapauttamiseksi. Tässä työssä on tarkasteltu amfifiilisten tähtipolymeerien itsejärjestymistä vesiliuoksissa sekä kokeellisesti ja tietokonesimulaatioin. Työ koostuu kahdesta osasta: tähtipolymeerien synteesistä makrosyklisillä initiaattoreilla ja amfifiilisten tähtimäisten blokkikopolymeerien ominaisuuksien tutkimisesta.