A Practical Micro Mechanical Model Based Local Approach Methodology for the Analysis of Ductile Fracture of Welded T-Joints

This thesis concentrates on developing a practical local approach methodology based on micro mechanical models for the analysis of ductile fracture of welded joints. Two major problems involved in the local approach, namely the dilational constitutive relation reflecting the softening behaviour of material, and the failure criterion associated with the constitutive equation, have been studied in detail. Firstly, considerable efforts were made on the numerical integration and computer implementation for the non trivial dilational Gurson Tvergaard model. Considering the weaknesses of the widely used Euler forward integration algorithms, a family of generalized mid point algorithms is proposed for the Gurson Tvergaard model. Correspondingly, based on the decomposition of stresses into hydrostatic and deviatoric parts, an explicit seven parameter expression for the consistent tangent moduli of the algorithms is presented. This explicit formula avoids any matrix inversion during numerical iteration and thus greatly facilitates the computer implementation of the algorithms and increase the efficiency of the code. The accuracy of the proposed algorithms and other conventional algorithms has been assessed in a systematic manner in order to highlight the best algorithm for this study. The accurate and efficient performance of present finite element implementation of the proposed algorithms has been demonstrated by various numerical examples. It has been found that the true mid point algorithm (a = 0.5) is the most accurate one when the deviatoric strain increment is radial to the yield surface and it is very important to use the consistent tangent moduli in the Newton iteration procedure. Secondly, an assessment of the consistency of current local failure criteria for ductile fracture, the critical void growth criterion, the constant critical void volume fraction criterion and Thomason's plastic limit load failure criterion, has been made. Significant differences in the predictions of ductility by the three criteria were found. By assuming the void grows spherically and using the void volume fraction from the Gurson Tvergaard model to calculate the current void matrix geometry, Thomason's failure criterion has been modified and a new failure criterion for the Gurson Tvergaard model is presented. Comparison with Koplik and Needleman's finite element results shows that the new failure criterion is fairly accurate indeed. A novel feature of the new failure criterion is that a mechanism for void coalescence is incorporated into the constitutive model. Hence the material failure is a natural result of the development of macroscopic plastic flow and the microscopic internal necking mechanism. By the new failure criterion, the critical void volume fraction is not a material constant and the initial void volume fraction and/or void nucleation parameters essentially control the material failure. This feature is very desirable and makes the numerical calibration of void nucleation parameters(s) possible and physically sound. Thirdly, a local approach methodology based on the above two major contributions has been built up in ABAQUS via the user material subroutine UMAT and applied to welded T joints. By using the void nucleation parameters calibrated from simple smooth and notched specimens, it was found that the fracture behaviour of the welded T joints can be well predicted using present methodology. This application has shown how the damage parameters of both base material and heat affected zone (HAZ) material can be obtained in a step by step manner and how useful and capable the local approach methodology is in the analysis of fracture behaviour and crack development as well as structural integrity assessment of practical problems where non homogeneous materials are involved. Finally, a procedure for the possible engineering application of the present methodology is suggested and discussed.

Kontekstitietoinen personalisointi mobiiliympäristössä

Tässä työssä selvitetään mitä mobiiliympäristössä käytettävillä kontekstitietoisilla sovelluksilla tarkoitetaan, miksi niitä tarvitaan ja mitä niiden avulla voidaan saavuttaa. Käyttäjäkeskeisen palvelun tavoitteena on mukautua käyttäjän kontekstiin, sekä hänen tarpeisiin ja tavoitteisiin ilman käyttäjältä vaadittavaa jatkuvaa vuorovaikutusta. Kontekstitietoisen sovelluksen suunnittelussa ja toteutuksessa tulee kiinnittää huomiota muun muassa kontekstitiedon keräämiseen, tallentamiseen ja tiedon eheyden säilyttämiseen. Sovelluksen suunnittelun tärkein haaste on toteuttaa hyvä logiikka, joka osaa päätellä kontekstitiedoista mitä toimintoja sen tulisi suorittaa. Mobiilipalveluiden personalisoinnissa on tärkeää ottaa huomioon käyttäjän, laitteen ja palvelun väliset vuorovaikutussuhteet. Nämä vuorovaikutussuhteet määrittelevät miten tiettyä mobiilipalvelua tulisi personalisoida jotta palvelu pystyy täyttämään käyttäjän sille asettamat vaatimukset.

Azimuth thrusterin rungon lujuustekninen tarkastelu

Työssä perehdyttiin azimuth potkurilaitteen rakenteelliseen kestävyyteen vaikuttaviin seikkoihin. Työn tavoitteena oli tutkia eri rakenneratkaisuja ja yksityiskohtia sekä niiden vaikutusta koko potkurilaitteen toimintaan. Potkurilaitteiden lujuustekninen tarkastelu sisälsi rakenteen eheyden tarkistuksen mekaanisten kuormitusten alla kuin myös värähtelykäyttäytymisen tutkimisen. Tarkastelun pääsääntöinen kohde oli potkurilaitteen alarunko, eli laivan ulkopuolelle jäävä osa. Diplomityö oli osa kahden uuden potkurilaitteen kehitysprojektia. Projektissa esiin tulleita rakennemuutoksia vertailtiin vanhoihin, jo toteutettuihin rakenneyksityiskohtiin. Lisäksi tutkittiin olemassa olevien rakenneratkaisujen hyödyntämistä uusissa laitteissa. Huomiota kiinnitettiin myös hitsien muotoiluun ja näiden mitoituskäytäntöihin. Rungon ehyyttä koskevat laskelman ovat hyvin pitkälti suoritettu elementtimenetelmää apuna käyttäen. Elementtimenetelmää varten luotiin useita malleja kattaen kokonaisia potkurilaittee runkoja kuin myös sen yksittäisiä osia. Elementtimenetelmän avulla saatuja tuloksia vertailtiin käytettävissä oleviin mittaustuloksiin. Työssä havaittiin potkurilaitteen rungon mitoittavaksi tekijäksi staattisessa tilanteessa muodostuvan voimansiirtolinja ja siinä sijaitsevien hammaspyörien siirtymät. Tämän seurauksena rungon taipumat ovat määräävämpiä geometrian kannalta kuin materiaalien sallitut jännitykset.

Tilintarkastajan riskienhallinta vaihto-omaisuuden tarkastuksessa

Tutkielman tavoitteena oli tutkia tilintarkastukseen kohdistuvia vaihto-omaisuuden riskejä ja niiden hallintaa. Tilintarkastajan riskienhallinta on tullut yhä tärkeämmäksi tilintarkastusskandaalien ja standardien vaatimusten tiukentumisen takia. Vaihto-omaisuus on yksi taseen merkittävimmistä eristä. Sen riskisyyteen vaikuttavia tekijöitä ovat esimerkiksi yrityksen toimiala ja epäkuranttiuden sekä vaihto-omaisuuden määrä. Tilintarkastuksen suunnittelu, olennaisuusmäärittely ja riskienarviointi ovat samanlaisia riippumatta asiakastoimeksiannon koosta, ja ne suoritetaan standardien mukaisesti. Tutkimuksen empiirisessä osassa haastateltiin viittä tilintarkastajaa. Empiirisen analyysin tulokset ovat pääasiassa samankaltaiset kirjallisuudesta saadun tiedon kanssa. Tutkimuksen perusteella voidaan todeta, että vaihto-omaisuuden riskit ovat yrityskohtaisia. Suurimmat riskit ovat yrityksissä, joissa sisäiset kontrollit ovat heikot tai jonka johdon rehellisyyteen ei voida luottaa.

Suunnitelma WWW-palvelun monikanavaistamiseksi

Tämän diplomityön tavoitteena on kuvata suunnitelma, jossa alun perin WWW-ympäristöön kehitettyä palvelua muokataan siten, että palvelu skaalautuu mahdollisimman hyvin tulevaisuuden laajennuksiin. Selainpohjaisten palveluiden lisäksi esimerkiksi mobiili-palvelut ja erilaiset työpöytäsovellusintegraatiot ovat kasvattaneet suosiotaan. Samoin eri palveluiden välisestä yhteistoiminnasta on kasvanut merkittävä osa Internet-palveluiden loppukäyttäjilleen tarjoamaa palvelukokonaisuutta. Esimerkkejä WWW-palveluiden integroinneista päätelaitteille ovat hakukoneiden ja pikaviestimien mobiili-versiot, ja palveluiden yhteistoiminnasta erilaisten uutispalveluiden ja sosiaalisten palveluiden, kuten Facebook, väliset yhteisölinkitykset. Tässä diplomityössä selvitetään aluksi Internet-pohjaisten palveluiden kehitystä sekä tutustutaan tarkemmin palveluiden monikanavaisuuteen. Tämän jälkeen käydään läpi loppukäyttäjien saatavilla olevia päätelaitteita verkkoyhteyksineen ja WWW-palveluiden suunnittelumalleja. Suunnittelun lähtökohtana oli se, että erilaisten päätelaitteiden, päätelaitteiden ohjelmistojen ja käytössä olevien verkkoyhteyksien muodostamien palvelualustojen liittäminen palveluun olisi mahdollisimman yksinkertaista. Ja tukea uusien palvelualustojen käyttäjien ja sisällön sovittamista olemassa olevaan palveluun. Työn lopputuloksena on suunnitelma, joka pohjautuu välikerroksen rakentamiseen uusien palvelualustojen ja vanhan palvelun väliin. Palveluun tarjotaan välikerroksen kautta personoitu rajapinta luotetuille asiakkaille sekä kaikille avoin julkinen rajapinta. Välikerros suunniteltiin yksinkertaisella REST-arkkitehtuurityylillä, mikä mahdollistaa palvelun tarjonnan turvallisesti ja tehokkaasti. Tähän välikerrokseen lisätään käyttäjän- ja sisällönhallinnan komponentteja pitämään huolen palvelun eheydestä. Tämä diplomityö osoittaa, että oikealla arkkitehtuurilla suunniteltu monikerroksinen väliohjelmisto tarjoaa tehokkaan tavan integroida ja hallinnoida uusia alustoja.

Nuclear Matrix in Apoptotic Cell Death and Cell Proliferation. The role of Nuclear Mitotic Apparatus (NuMA) Protein

The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.

A cell spot microarray method for high-throughput biology

High-throughput screening of cellular effects of RNA interference (RNAi) libraries is now being increasingly applied to explore the role of genes in specific cell biological processes and disease states. However, the technology is still limited to specialty laboratories, due to the requirements for robotic infrastructure, access to expensive reagent libraries, expertise in high-throughput screening assay development, standardization, data analysis and applications. In the future, alternative screening platforms will be required to expand functional large-scale experiments to include more RNAi constructs, allow combinatorial loss-of-function analyses (e.g. genegene or gene-drug interaction), gain-of-function screens, multi-parametric phenotypic readouts or comparative analysis of many different cell types. Such comprehensive perturbation of gene networks in cells will require a major increase in the flexibility of the screening platforms, throughput and reduction of costs. As an alternative for the conventional multi-well based high-throughput screening -platforms, here the development of a novel cell spot microarray method for production of high density siRNA reverse transfection arrays is described. The cell spot microarray platform is distinguished from the majority of other transfection cell microarray techniques by the spatially confined array layout that allow highly parallel screening of large-scale RNAi reagent libraries with assays otherwise difficult or not applicable to high-throughput screening. This study depicts the development of the cell spot microarray method along with biological application examples of high-content immunofluorescence and phenotype based cancer cell biological analyses focusing on the regulation of prostate cancer cell growth, maintenance of genomic integrity in breast cancer cells, and functional analysis of integrin protein-protein interactions in situ.

Modeling and Analysis of Noise and Interconnects for On-Chip Communication Link Design

This thesis considers modeling and analysis of noise and interconnects in onchip communication. Besides transistor count and speed, the capabilities of a modern design are often limited by on-chip communication links. These links typically consist of multiple interconnects that run parallel to each other for long distances between functional or memory blocks. Due to the scaling of technology, the interconnects have considerable electrical parasitics that affect their performance, power dissipation and signal integrity. Furthermore, because of electromagnetic coupling, the interconnects in the link need to be considered as an interacting group instead of as isolated signal paths. There is a need for accurate and computationally effective models in the early stages of the chip design process to assess or optimize issues affecting these interconnects. For this purpose, a set of analytical models is developed for on-chip data links in this thesis. First, a model is proposed for modeling crosstalk and intersymbol interference. The model takes into account the effects of inductance, initial states and bit sequences. Intersymbol interference is shown to affect crosstalk voltage and propagation delay depending on bus throughput and the amount of inductance. Next, a model is proposed for the switching current of a coupled bus. The model is combined with an existing model to evaluate power supply noise. The model is then applied to reduce both functional crosstalk and power supply noise caused by a bus as a trade-off with time. The proposed reduction method is shown to be effective in reducing long-range crosstalk noise. The effects of process variation on encoded signaling are then modeled. In encoded signaling, the input signals to a bus are encoded using additional signaling circuitry. The proposed model includes variation in both the signaling circuitry and in the wires to calculate the total delay variation of a bus. The model is applied to study level-encoded dual-rail and 1-of-4 signaling. In addition to regular voltage-mode and encoded voltage-mode signaling, current-mode signaling is a promising technique for global communication. A model for energy dissipation in RLC current-mode signaling is proposed in the thesis. The energy is derived separately for the driver, wire and receiver termination.

Superoxide dismutase 3-mediated cell survival and proliferation

This dissertation studies the signaling events mediated by the extracellular superoxide dismutase (SOD3). SOD3 is an antioxidant enzyme which converts the harmful superoxide into hydrogen peroxide. Overproduction of these reactive oxygen species (ROS) in the cellular environment as a result of tissue injury or impaired antioxidant defense system has detrimental effects on tissue integrity and function. However, especially hydrogen peroxide is also an important signaling agent. Ischemic injury in muscle causes acute oxidative stress and inflammation. We investigated the ability of SOD3 to attenuate ischemia induced inflammation and to promote recovery of skeletal muscle tissue. We found that SOD3 can downregulate the expression of several inflammatory cytokines and cell adhesion molecules thus preventing the accumulation of oxidant-producing inflammatory cells. Secondly, SOD3 was able to promote long-term activation of the mitogenic Erk pathway, but increased only briefly the activity of pro-survival Akt pathway at an early stage of ischemic inflammation, thus reducing apoptosis. SOD3 is a prominent antioxidant in the thyroid gland where oxidative stress is constantly present. We investigated the role of SOD3 in normal thyroid follicular cells and the changes in its expression in various hyperproliferative disorders. We first showed that SOD3 is TSH-responsive which indicated its participation in thyroid function. Its principal function seems to be in follicular cell proliferation since knockdown cells were deficient in proliferation. Additionally, it was overexpressed in goiter tissue. However, SOD3 was consistently downregulated in thyroid cancer cell lines and tissues. In conclusion, SOD3 is involved in tissue maintenance, cell proliferation and inflammatory cell migration. Its mechanisms of action are the activation of known proliferation/survival pathways, inhibition of apoptosis and regulation of adhesion molecule expression.

Nuorten johtajien johtamiskäytänteet asiantuntijaorganisaatioissa

Johtajasukupolvet ovat vaihtumassa ja tulevaisuudessa tarvitaan yhä useampia nuoria johtajia täyttämään johtajien paikkoja. Tämä tutkimus osallistuu nuorista johtajista ja tällä hetkellä työelämässä olevasta nuorimmasta sukupolvesta käytävään tieteelliseen ja yhteiskunnalliseen keskusteluun. Tutkimuksen tavoitteena on kuvata ja ymmärtää nuorten johtajien johtamiskäytänteitä asiantuntijaorganisaatioissa. Tutkimuksen on luonteeltaan kvalitatiivinen ja sen pääasiallinen aineisto koostuu kymmenen nuoren johtajan haastatteluista. Tutkimuksen mukaan nuoret johtajat ovat eettisiä ja autenttisia johtajia, jotka arvostavat johtamisessaan yhä enemmän niin sanottuja pehmeitä arvoja, kuten oikeudenmukaisuutta, avoimuutta, ihmisten kehittämistä, kuuntelutaitoa ja muiden huomioon ottamista sekä kykyä inspiroida. Nuoren johtajan tapa johtaa on valmentavaa ja esimerkillä johtamista, joka perustuu ennen kaikkea valtuuttamiselle ja yhteistyölle alaisten kanssa.

Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.

Repair of segmental bone defects with fiber-reinforced composite: a study of material development and an animal model on rabbits

The Repair of segmental defects in load-bearing long bones is a challenging task because of the diversity of the load affecting the area; axial, bending, shearing and torsional forces all come together to test the stability/integrity of the bone. The natural biomechanical requirements for bone restorative materials include strength to withstand heavy loads, and adaptivity to conform into a biological environment without disturbing or damaging it. Fiber-reinforced composite (FRC) materials have shown promise, as metals and ceramics have been too rigid, and polymers alone are lacking in strength which is needed for restoration. The versatility of the fiber-reinforced composites also allows tailoring of the composite to meet the multitude of bone properties in the skeleton. The attachment and incorporation of a bone substitute to bone has been advanced by different surface modification methods. Most often this is achieved by the creation of surface texture, which allows bone growth, onto the substitute, creating a mechanical interlocking. Another method is to alter the chemical properties of the surface to create bonding with the bone – for example with a hydroxyapatite (HA) or a bioactive glass (BG) coating. A novel fiber-reinforced composite implant material with a porous surface was developed for bone substitution purposes in load-bearing applications. The material’s biomechanical properties were tailored with unidirectional fiber reinforcement to match the strength of cortical bone. To advance bone growth onto the material, an optimal surface porosity was created by a dissolution process, and an addition of bioactive glass to the material was explored. The effects of dissolution and orientation of the fiber reinforcement were also evaluated for bone-bonding purposes. The Biological response to the implant material was evaluated in a cell culture study to assure the safety of the materials combined. To test the material’s properties in a clinical setting, an animal model was used. A critical-size bone defect in a rabbit’s tibia was used to test the material in a load-bearing application, with short- and long-term follow-up, and a histological evaluation of the incorporation to the host bone. The biomechanical results of the study showed that the material is durable and the tailoring of the properties can be reproduced reliably. The Biological response - ex vivo - to the created surface structure favours the attachment and growth of bone cells, with the additional benefit of bioactive glass appearing on the surface. No toxic reactions to possible agents leaching from the material could be detected in the cell culture study when compared to a nontoxic control material. The mechanical interlocking was enhanced - as expected - with the porosity, whereas the reinforcing fibers protruding from the surface of the implant gave additional strength when tested in a bone-bonding model. Animal experiments verified that the material is capable of withstanding load-bearing conditions in prolonged use without breaking of the material or creating stress shielding effects to the host bone. A Histological examination verified the enhanced incorporation to host bone with an abundance of bone growth onto and over the material. This was achieved with minimal tissue reactions to a foreign body. An FRC implant with surface porosity displays potential in the field of reconstructive surgery, especially regarding large bone defects with high demands on strength and shape retention in load-bearing areas or flat bones such as facial / cranial bones. The benefits of modifying the strength of the material and adjusting the surface properties with fiber reinforcement and bone-bonding additives to meet the requirements of different bone qualities are still to be fully discovered.

Uutta tietoa Kainuun soista : Kainuun suoselvitys -projektin tulosraportti

Raportissa esitellään Kainuun suoselvitys -projektin keskeisimpiä tuloksia ja niistä vedettyjä johtopäätöksiä. Vuosina 2010–2012 toteutetun projektin tarkoituksena on ollut parantaa tietopohjaa Kainuun soista, ja sitä kautta luoda edellytyksiä soiden eri käyttömuotojen yhteensovittamiselle ja samalla nostaa esille Kainuun soihin liittyviä mahdollisuuksia. Soiden käyttö nähtiin projektissa laajasti, sisältäen paitsi erilaiset taloudellisen hyödyntämisen muodot myös soiden merkityksen ihmisten virkistykselle ja hyvinvoinnille sekä luonnon monimuotoisuudelle ja monille sääteleville toiminnoille. Taustana projektille on samaan aikaan laadittu kansallinen suostrategia. Sen mukaan soiden luonnontilaa muuttavien toimintojen, maa-, metsä- ja turvetalouden, tulisi jatkossa toimia jo ojitetuilla tai muuten merkittävästi muuttuneilla soilla. Näin soiden luonnontilaisuudesta hyötyville soiden käytön muodoille ja ekosysteemipalveluille jää paremmin tilaa toimia. Kainuu on Suomen kolmanneksi soisin maakunta. Suot ovat keskeinen osa sen luontoa ja maisemaa ja myös monipuolinen luonnonvara. Valtaosa Kainuun suopinta-alasta on ojitettu. Uutta tietoa on projektissa tuotettu paikkatietomenetelmin ja kohdennetuin maastoselvityksin. Raportin aihepiirejä ovat Kainuun soiden käyttö, jäljellä olevat ojittamattomat suot, suojeltujen soiden vesitaloudellinen eheys, metsätalouden käytöstä poistuvat ojitetut suot, soiden merkitys virkistyksen ja matkailun kannalta sekä maastossa tutkittujen 143 suon arviointi turpeennoston ja luonnon monimuotoisuuden kannalta. Raportissa esitetään, että kansallisen suostrategian tavoite soiden kestävästä ja vastuullisesta käytöstä ja suojelusta on mahdollista saavuttaa eri toimijoiden yhteistyön ja maankäytön ohjauksen avulla. Se edellyttää sitoutumista suostrategian linjauksiin sekä tietopohjan parantamista soista ja eri toimintojen vaikutuksista. Kainuun suoselvitys -projektissa on osaltaan tuotettu tätä tietoa ja myös kehitelty menetelmiä sen hankkimiseksi.

Detection of Pathologic Changes Following Traumatic Brain Injury Using Magnetic Resonance Imaging

Background: Approximately two percent of Finns have sequels after traumatic brain injury (TBI), and many TBI patients are young or middle-aged. The high rate of unemployment after TBI has major economic consequences for society, and traumatic brain injury often has remarkable personal consequences, as well. Structural imaging is often needed to support the clinical TBI diagnosis. Accurate early diagnosis is essential for successful rehabilition and, thus, may also influence the patient’s outcome. Traumatic axonal injury and cortical contusions constitute the majority of traumatic brain lesions. Several studies have shown magnetic resonance imaging (MRI) to be superior to computed tomography (CT) in the detection of these lesions. However, traumatic brain injury often leads to persistent symptoms even in cases with few or no findings in conventional MRI. Aims and methods: The aim of this prospective study was to clarify the role of conventional MRI in the imaging of traumatic brain injury, and to investigate how to improve the radiologic diagnostics of TBI by using more modern diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) techniques. We estimated, in a longitudinal study, the visibility of the contusions and other intraparenchymal lesions in conventional MRI at one week and one year after TBI. We used DWI-based measurements to look for changes in the diffusivity of the normal-appearing brain in a case-control study. DTI-based tractography was used in a case-control study to evaluate changes in the volume, diffusivity, and anisotropy of the long association tracts in symptomatic TBI patients with no visible signs of intracranial or intraparenchymal abnormalities on routine MRI. We further studied the reproducibility of different tools to identify and measure white-matter tracts by using a DTI sequence suitable for clinical protocols. Results: Both the number and extent of visible traumatic lesions on conventional MRI diminished significantly with time. Slightly increased diffusion in the normal-appearing brain was a common finding at one week after TBI, but it was not significantly associated with the injury severity. Fractional anisotropy values, that represent the integrity of the white-matter tracts, were significantly diminished in several tracts in TBI patients compared to the control subjects. Compared to the cross-sectional ROI method, the tract-based analyses had better reproducibility to identify and measure white-matter tracts of interest by means of DTI tractography. Conclusions: As conventional MRI is still applied in clinical practice, it should be carried out soon after the injury, at least in symptomatic patients with negative CT scan. DWI-related brain diffusivity measurements may be used to improve the documenting of TBI. DTI tractography can be used to improve radiologic diagnostics in a symptomatic TBI sub-population with no findings on conventional MRI. Reproducibility of different tools to quantify fibre tracts vary considerably, which should be taken into consideration in the clinical DTI applications.

The Effects of Estradiol, Androgens and the Selective Estrogen Modulators: Ospemifene, Raloxifene and Tamoxifen on Explant Cultures of Human Breast Tissue

The impact of menopausal hormone therapy (MHT) on increasing the risk for breast cancer (BC) remains controversial. To understand MHT-elicited cellular breast effects and the potential risks, included with using this therapy, a further investigation into this controversy is the subject of this thesis. In this thesis, to study the effects of estrogen, progestin, androgens and selective estrogen receptor modulators (SERMs), a modified tissue explant culture system was used. The different types of human breast tissues (HBTs) used in this study were normal HBTs, obtained from reduction mammoplasties of premenopausal women (prem-HBTs) or postmenopausal (postm-HBTs) women and peritumoral HBTs (peritum-HBTs) which were obtained from surgeries on postmenopausal BC patients. The explants were cultured up to three weeks in the presence or absence of estradiol (E2), medroxyprogesterone acetate (MPA), testosterone (T), dihydrotestosterone (DHT) and SERMs - ospemifene (OSP), raloxifene (RAL) and tamoxifen (TAM). The cultured HBTs maintained morphological integrity and responded to hormonal treatment in vitro. E2, MPA or E2/MPA increased proliferative activity and was associated with increased cyclin-D1 and caused changes in the cell cycle inhibitors p21 and p27, whereas the androgens T and DHT inhibited proliferation and increased apoptosis in HBT epithelia and opposed E2-stimulated proliferation and cell survival. The postm-HBTs were more sensitive to E2 than prem-HBTs. The effects of OSP, RAL and TAM on HBT epithelium were antiproliferative. E2, androgens and SERMs were associated with marked changes in the proportions of epithelial cells expressing steroid hormone receptors: E2 increased ERα expressing cells and decreased androgen receptor (AR) positive cells, whereas T and DHT had opposite effects. The OSP, RAL and TAM, also decreased a proportion of ERα positive cells in HBT epithelium. At 100 nM, these compounds maintained the relative number of AR positive cells, present at control level, which may partly explain proliferative inhibition. In conclusion, the proliferative activity of E2, in the epithelium of postm-HBTs, is opposed by T and DHT, which suggests that the inclusion of androgens in MHT may decrease the risk for developing BC.