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  • Würtz, Peter (Helsingin yliopisto, 2008)
    NMR spectroscopy enables the study of biomolecules from peptides and carbohydrates to proteins at atomic resolution. The technique uniquely allows for structure determination of molecules in solution-state. It also gives insights into dynamics and intermolecular interactions important for determining biological function. Detailed molecular information is entangled in the nuclear spin states. The information can be extracted by pulse sequences designed to measure the desired molecular parameters. Advancement of pulse sequence methodology therefore plays a key role in the development of biomolecular NMR spectroscopy. A range of novel pulse sequences for solution-state NMR spectroscopy are presented in this thesis. The pulse sequences are described in relation to the molecular information they provide. The pulse sequence experiments represent several advances in NMR spectroscopy with particular emphasis on applications for proteins. Some of the novel methods are focusing on methyl-containing amino acids which are pivotal for structure determination. Methyl-specific assignment schemes are introduced for increasing the size range of 13C,15N labeled proteins amenable to structure determination without resolving to more elaborate labeling schemes. Furthermore, cost-effective means are presented for monitoring amide and methyl correlations simultaneously. Residual dipolar couplings can be applied for structure refinement as well as for studying dynamics. Accurate methods for measuring residual dipolar couplings in small proteins are devised along with special techniques applicable when proteins require high pH or high temperature solvent conditions. Finally, a new technique is demonstrated to diminish strong-coupling induced artifacts in HMBC, a routine experiment for establishing long-range correlations in unlabeled molecules. The presented experiments facilitate structural studies of biomolecules by NMR spectroscopy.
  • Satama, Mikko (Helsingin yliopisto, 2009)
    The aim of this thesis is to analyse the key ecumenical dialogues between Methodists and Lutherans from the perspective of Arminian soteriology and Methodist theology in general. The primary research question is defined as: "To what extent do the dialogues under analysis relate to Arminian soteriology?" By seeking an answer to this question, new knowledge is sought on the current soteriological position of the Methodist-Lutheran dialogues, the contemporary Methodist theology and the commonalities between the Lutheran and Arminian understanding of soteriology. This way the soteriological picture of the Methodist-Lutheran discussions is clarified. The dialogues under analysis were selected on the basis of versatility. Firstly, the sole world organisation level dialogue was chosen: The Church – Community of Grace. Additionally, the document World Methodist Council and the Joint Declaration on the Doctrine of Justification is analysed as a supporting document. Secondly, a document concerning the discussions between two main-line churches in the United States of America was selected: Confessing Our Faith Together. Thirdly, two dialogues between non-main-line Methodist churches and main-line Lutheran national churches in Europe were chosen: Fellowship of Grace from Norway and Kristuksesta osalliset from Finland. The theoretical approach to the research conducted in this thesis is systematic analysis. The Remonstrant articles of Arminian soteriology are utilised as an analysis tool to examine the soteriological positions of the dialogues. New knowledge is sought by analysing the stances of the dialogues concerning the doctrines of partial depravity, conditional election, universal atonement, resistible grace and conditional perseverance of saints. This way information is also provided for approaching the Calvinist-Arminian controversy from new perspectives. The results of this thesis show that the current soteriological position of the Methodist-Lutheran dialogues is closer to Arminianism than Calvinism. The dialogues relate to Arminian soteriology especially concerning the doctrines of universal atonement, resistible grace and conditional perseverance of saints. The commonalities between the Lutheran and Arminian understanding of soteriology exist mainly in these three doctrines as they are uniformly favoured in the dialogues. The most discussed area of soteriology is human depravity, in which the largest diversity of stances occurs as well. On the other hand, divine election is the least discussed topic. The overall perspective, which the results of the analysis provide, indicates that the Lutherans could approach the Calvinist churches together with the Methodists with a wider theological perspective and understanding when the soteriological issues are considered as principal. Human depravity is discovered as the area of soteriology which requires most work in future ecumenical dialogues. However, the detected Lutheran hybrid notion on depravity (a Calvinist-Arminian mixture) appears to provide a useful new perspective for Calvinist-Arminian ecumenism and offers potentially fruitful considerations to future ecumenical dialogues.
  • Hänninen, Teemu (Helsingin yliopisto, 2006)
    The concept of an atomic decomposition was introduced by Coifman and Rochberg (1980) for weighted Bergman spaces on the unit disk. By the Riemann mapping theorem, functions in every simply connected domain in the complex plane have an atomic decomposition. However, a decomposition resulting from a conformal mapping of the unit disk tends to be very implicit and often lacks a clear connection to the geometry of the domain that it has been mapped into. The lattice of points, where the atoms of the decomposition are evaluated, usually follows the geometry of the original domain, but after mapping the domain into another this connection is easily lost and the layout of points becomes seemingly random. In the first article we construct an atomic decomposition directly on a weighted Bergman space on a class of regulated, simply connected domains. The construction uses the geometric properties of the regulated domain, but does not explicitly involve any conformal Riemann map from the unit disk. It is known that the Bergman projection is not bounded on the space L-infinity of bounded measurable functions. Taskinen (2004) introduced the locally convex spaces LV-infinity consisting of measurable and HV-infinity of analytic functions on the unit disk with the latter being a closed subspace of the former. They have the property that the Bergman projection is continuous from LV-infinity onto HV-infinity and, in some sense, the space HV-infinity is the smallest possible substitute to the space H-infinity of analytic functions. In the second article we extend the above result to a smoothly bounded strictly pseudoconvex domain. Here the related reproducing kernels are usually not known explicitly, and thus the proof of continuity of the Bergman projection is based on generalised Forelli-Rudin estimates instead of integral representations. The minimality of the space LV-infinity is shown by using peaking functions first constructed by Bell (1981). Taskinen (2003) showed that on the unit disk the space HV-infinity admits an atomic decomposition. This result is generalised in the third article by constructing an atomic decomposition for the space HV-infinity on a smoothly bounded strictly pseudoconvex domain. In this case every function can be presented as a linear combination of atoms such that the coefficient sequence belongs to a suitable Köthe co-echelon space.
  • Franti, Lasse (Helsingin yliopisto, 2015)
    The gauge/gravity duality connects the dynamics of gravity theories in the bulk with the dynamics of field theories on the boundary. In this thesis we introduce two thermalization scenarios and investigate them using a suitable holographic description. We will first study the thermalization of equal-time correlators and entanglement entropy in a hyperscaling violating AdS-Lifshitz-Vaidya metric. This work verifies the agreement between numerical procedures and preceding analytical predictions and generalises the previous studies of thermalization in this kind of situations. In the latter part we will use the duality to describe the quark-qluon plasma created in heavy ion collisions. The anisotropic plasma is modelled by introducing anisotropies into the source on the gravity side and letting them evolve according to the equations of motion. The boundary dynamics is extracted by finding the boundary stress-energy tensor. The results agree with the conventional models. The situations considered here are rather simple but this work demonstrates the applicability of holography in the anisotropic case.
  • Nurmi, Sami (Helsingin yliopisto, 2008)
    Cosmological inflation is the dominant paradigm in explaining the origin of structure in the universe. According to the inflationary scenario, there has been a period of nearly exponential expansion in the very early universe, long before the nucleosynthesis. Inflation is commonly considered as a consequence of some scalar field or fields whose energy density starts to dominate the universe. The inflationary expansion converts the quantum fluctuations of the fields into classical perturbations on superhorizon scales and these primordial perturbations are the seeds of the structure in the universe. Moreover, inflation also naturally explains the high degree of homogeneity and spatial flatness of the early universe. The real challenge of the inflationary cosmology lies in trying to establish a connection between the fields driving inflation and theories of particle physics. In this thesis we concentrate on inflationary models at scales well below the Planck scale. The low scale allows us to seek for candidates for the inflationary matter within extensions of the Standard Model but typically also implies fine-tuning problems. We discuss a low scale model where inflation is driven by a flat direction of the Minimally Supersymmetric Standard Model. The relation between the potential along the flat direction and the underlying supergravity model is studied. The low inflationary scale requires an extremely flat potential but we find that in this particular model the associated fine-tuning problems can be solved in a rather natural fashion in a class of supergravity models. For this class of models, the flatness is a consequence of the structure of the supergravity model and is insensitive to the vacuum expectation values of the fields that break supersymmetry. Another low scale model considered in the thesis is the curvaton scenario where the primordial perturbations originate from quantum fluctuations of a curvaton field, which is different from the fields driving inflation. The curvaton gives a negligible contribution to the total energy density during inflation but its perturbations become significant in the post-inflationary epoch. The separation between the fields driving inflation and the fields giving rise to primordial perturbations opens up new possibilities to lower the inflationary scale without introducing fine-tuning problems. The curvaton model typically gives rise to relatively large level of non-gaussian features in the statistics of primordial perturbations. We find that the level of non-gaussian effects is heavily dependent on the form of the curvaton potential. Future observations that provide more accurate information of the non-gaussian statistics can therefore place constraining bounds on the curvaton interactions.
  • Keränen, Petteri (Helsingin yliopisto, 1999)
  • Lehtonen, Jaakko (1970)
  • Hemming, Samuli (Helsingin yliopisto, 2004)
  • Rusak, Stanislav (Helsingin yliopisto, 2015)
    Grounded in the increasingly accurate astronomical observations of the past few decades, the study of cosmology has produced a comprehensive account of the history of the universe. This account is contained in the Hot Big Bang cosmological model which describes the expansion of a hot and dense state to become the universe as we observe it today. While the Big Bang model has been extremely successful in being able to account for a wide array of cosmological data, it leaves unexplained the special initial conditions that are required in order to produce the universe we find ourselves in. Such initial conditions are, however, a natural consequence of a period of quasi-exponential expansion of the universe known as inflation. Such a period of expansion can be realized if the universe is dominated by a scalar field - the inflation - which is slowly rolling down the slope of its potential. Inflation also provides a natural mechanism for the production of primordial seeds of structure in the universe through the growth of the quantum fluctuations in the inflaton field to super-horizon scales. Together inflation and the subsequent Big Bang evolution form the back bone of modern cosmology. However, the transition between the inflationary epoch and the thermal state which characterizes the initial conditions of the Big Bang evolution is not well understood. This process - dubbed reheating - involves the decay of the inflaton field into the particles of the Standard Model of particle physics, and may be highly non-trivial, with non-perturbative resonant processes playing a major role. Spectator fields - light scalar fields which are subdominant during inflation - may also play an important role during this epoch. The aim of this thesis is to showcase aspects of non-perturbative decay of scalar fields after inflation, focusing in particular on the role of spectator fields. This includes the modulation of the non-perturbative decay of the inflaton by a spectator field, the non-perturbative decay of a spectator into the Standard Model Higgs, as well as the non-perturbative decay of the Higgs field itself.
  • Rüppell, Timo (Helsingin yliopisto, 2013)
    Supersymmetry is a widely used extension of the Standard Model of particle physics. It extends the Standard Model by adding a symmetry between bosonic and fermionic particles and introduces superpartners -- particles with similar quantum numbers but opposite spin statistics -- for each of the Standard Model fields. The scalar partners of Standard Model particles allow for the construction of Lorentz and gauge invariant terms in the Lagrangian that break symmetries (or near symmetries) of the Standard Model, such as CP, flavor, baryon number, and lepton number. This presents both a challenge in explaining the absence of large symmetry breaking effects, and an opportunity for indirect discovery of Supersymmetry in precision experiments. In the Standard Model the mentioned symmetries are accidental and unrelated. In a supersymmetric model they must be specifically reinstated and dynamically broken, or be otherwise constrained. As a consequence, these symmetries can become linked via the specifics of their breaking mechanisms. The subject of this thesis is the construction of models where this happens and the consequent relationships between symmetry breaking observables as well as the effects on other phenomenologically interesting quantities, such as Dark Matter and neutrino masses. The first part of the thesis is an introduction to the Standard Model, and the second part details the specifics of supersymmetric model building. The third part introduces the subject matter of the papers included in this thesis and presents some of the papers' key findings.
  • Helminen, Christina (Helsingin yliopisto, 2000)
  • Tisler, Priit (Helsingin yliopisto, 2006)
  • Aro, Katri (Helsingin yliopisto, 2012)
    According to the Finnish Cancer Registry, salivary gland cancer (SGC) is rare, with approximately 50 to 60 new cases in Finland annually. For pediatric patients, the Finnish Cancer Registry reported 15 new cases between 1990 and 2009. The wide spectrum of different subtypes makes this group of diseases difficult to diagnose, grade, and treat. Due to the rarity of these diseases, no specific risk factors are known, and long-term outcome data are difficult to obtain. In adults, 20% of parotid gland tumors, 50% of submandibular gland tumors, and 90% of sublingual gland tumors are malignant. Most tumors of the minor salivary glands are malignant. However, in the pediatric patient population, 50% of parotid gland tumors are malignant, but only 10% of submandibular gland tumors do. Mucoepidermoid carcinoma (MEC) is the most common (29 to 35%) malignant neoplasm of the major and minor salivary glands in both adults and children. According to the WHO, MEC is classified into three grades: low grade (LG), intermediate grade (IMG), and high grade (HG). These three grades have different growth potentials as well as different potentials to metastasize and to recur; consequently, they show major differences in outcome. Correct histopathological diagnosis thus remains vital. We evaluated the prevalence, treatment, and outcome of 52 Finnish patients with MEC of the major salivary glands. All LG-MECs (23/52) were localized to the primary site, and most patients with LG-MEC were treated and cured surgically. The three-year overall survival rate was 95% for LG-MEC, 67% for IMG-MEC, and 55% for HG-MEC patients. Patients with LG-MEC experienced no recurrences during the three-year follow up. IMG-MEC (7/52) more closely resembled HG-MEC (20/52) in its biological behavior, contradicting reports from other institutions. Patients with IMG-MEC had cervical nodal metastases in 43% of cases, and 67% developed locoregional or distant metastases during follow up. Radiotherapy was administered for 86% of IMG-MEC patients. In the HG-MEC group, nodal metastases were present at presentation in 50% of patients, and 80% also received radiotherapy. Our results suggest an aggressive treatment protocol for IMG-MEC, and that surgery seems adequate for LG-MEC. Claudins are integral protein components of tight junctions contributing to tight sealing between cells. Deregulation of claudins leads to loss of cell integrity, uncontrolled cell proliferation, advantageous potential for tumor growth and metastatic potential. No previous studies have explored the possible role of claudins in SGC. Immunohistochemical studies on claudins 1, 3, 4, and 7 for 39 major salivary gland MEC patients have revealed statistically significant differences in staining intensities. The high intensity for claudin-1 increased the likelihood of LG tumors with a favorable prognosis. HG- and IMG-MEC tumors more often had higher intensities for claudin-3, portending a worse prognosis. This feature again emphasizes that IMG-MEC differs from LG-MEC. Claudins may, therefore, aid in grading tumors correctly and also serve as surrogate prognostic protein markers. The extent of immunostaining had less impact on grading than anticipated. The intensity of claudin-1 immunostaining classified tumors correctly in 90% of cases corresponding to conventional histopathological features. Between 1992 and 2011, 10 new pediatric SGC cases were identified. No gender predominated, and the median age was 14 years. The majority of SGC cases were parotid gland tumors (7/10); all tumors were LG and localized to the primary site. No recurrences occurred during the 7-month to 14-year follow up. MEC was the most common histological subtype (50%), which reflects results from other institutions. Because pediatric SGC is infrequent, experience with and guidelines for managing pediatric cases must be adapted from guidelines for adults with SGC. Establishing national or international cancer databases could offer help in managing these rare diseases. Between 1974 and 2009, information was retrieved on 437 sequential SGC patients treated at the Helsinki University Central Hospital. Due to the long time period and the most often elderly patients, many were deceased at the time of the study. Consequently, the study cohort consisted of 161 patients who were alive and able to reach. Of these, 88 (55%) answered a patient questionnaire to identify possible hereditary forms of SGC as well as elevated risk for other malignancies among the relatives of SGC patients. The enquiry revealed no cases of SGC in first-degree relatives. Thus, most likely no significant familial predisposition for SGC exists in Finland.
  • Ovaska, Heidi (Helsingfors universitet, 2010)
    Pro gradu -tutkielmani tehtävänä on selvittää näkökulmia melankoliaterapiaan Martti Lutherin lohdutuskirjeissä. Lähteinä on ollut neljä lohdutuskirjettä sekä yksi kirje, joka muistuttaa sisällöltään lohdutuskirjettä. Metodina on ollut kirjeiden tyylillis-retorinen analyysi. Aihe on kiinnostava, koska Lutherin kirjeiden ja retoriikan tutkimus on ollut vähäistä verrattuna häntä koskevaan laajaan kansainväliseen tutkimukseen. Työn lähtökohtana on ollut, että yksi kirjallisuuden tärkeimmistä tehtävistä 1500-luvulla oli erilaisten melankolisten sairauksien parantaminen. Kirjallisuuden avulla voitiin torjua hengenvaarallisia melankolisia affekteja kuten epätoivoa, pelkoa, surua ja apatiaa. Lutherin lohdutuskirjeet soveltuvat hyvin melankoliaterapian tutkimiseen, koska ne on kirjoitettu lohtua tarvitseville ihmisille. Työn tutkimuskysymykset ovat: Mitä melankolian hoitokeinoja Luther mainitsee? Missä määrin Lutherin melankoliaterapia on sopusoinnussa 1500-luvulla vallinneiden hoitokäsitysten kanssa? Miten Luther hyödyntää retoriikan ja huumorin keinoja melankoliaterapiassaan? Työn teoriaosassa selvitetään 1500-luvun ihmiskäsitystä sekä teologisesta että lääketieteellisestä näkökulmasta ja esitellään ajalle tyypillisiä humoraaliopin mukaisia melankolian hoitokeinoja. Selvitetään myös retoriikan ja melankoliaterapian suhdetta toisiinsa. Analyysiosassa pääpaino on Lutherin käyttämissä retorisissa keinoissa, mutta siinä hyödynnetään myös teoriaosan havaintoja. Tutkielmassa kirjallisuustieteellinen ja teologinen näkökulma tukevat toisiaan. Kirjallisuustieteellisestä näkökulmasta lohdutuskirjeet on tutkittavissa retoriikan tarjoamien käsitteiden avulla, koska ne on kirjoitettu aikana, jolloin retoriikka oli tärkeä yliopistollinen oppiaine. Tutkielma huomioi myös aiheen teologisen näkökulman, koska ajan kieli on uskonnollisesti värittynyttä ja koska Lutherin melankoliaterapiaan kuuluu vahva hengellinen ulottuvuus. Ihmisen kyky lohduttaa rinnastuu Lutherilla Jumalan kykyyn lohduttaa ihmistä Raamatun sanan kautta. Lutherille Jumala on reetori, jonka työväline on Raamatun pyhä sana. Puhutulla ja kirjoitetulla sanalla on Lutherin melankoliaterapiassa erityisen keskeinen merkitys. Tutkielmani osoittaa, että sekä Lutherin käyttämät retoriset keinot että hänen melankoliaterapiansa ovat suuressa määrin sopusoinnussa 1500-luvun retoriikan ja lääketieteen oppien kanssa. Luther käyttää melankoliaterapiassaan laajasti apuna erilaisia retorisia keinoja kuten toistoa, variaatiota, metaforaa ja esimerkkikertomuksia. Lutherin mainitsemat hoitokeinot kuten esimerkiksi metsästys, ratsastus, syöminen ja juominen, pelien pelaaminen, leikinlasku ja ystävien kanssa seurustelu ovat sopusoinnussa ajan hoitokäsitysten kanssa. Kirjeissä esiintyy myös lääketieteellisestä ja uskonnollisesta näkökulmasta katsottuna kyseenalaisia hoitokeinoja kuten tyhjänpäiväisten juttujen kertominen ja paholaisen kiroileminen. Nämä neuvot ylittävät ajan melankoliaterapiaan kuuluvan kohtuullisuuden säännön, ja ne on ymmärrettävä niiden teologisesta merkityksestä käsin. Lutherille kohtuullisuuden säännön rikkominen on toisinaan sallittua, kun on kysymys vaikeasta paholaisen aiheuttamasta melankoliasta. Kristillinen usko näyttää Lutherille tarjoavan vapauden käyttää tiettyjä hoitokeinoja, joita vielä keskiajalla ei olisi hyväksytty. Toisinaan Luther näkee kirjeen vastaanottajaa kohdanneen vaikeuden Jumalan eikä paholaisen aikaansaannoksena. Tällaisissa tapauksissa melankolia nähdään Jumalan työnä ihmisessä, joka mahdollistaa hengellisen kääntymisen Jumalan, kaiken lohdutuksen Isän puoleen.
  • Miemois, Johanna (1997)
    Arbetet består av en litteraturstudie i ämnet hundhållning. Olika aspekter kring hållning av hundar diskuteras utgående från hundens behov och välmående. Förutom hundens direkta fysiska miljö diskuteras även dess psykosociala behov. Valpens utveckling och betydelse av en kvalitetsmiljö tas upp i texten. Orsaker till stress för hunden och följder av detta är en viktig del av hundhållningen, likaså hur detta kan åtgärdas. Förutom direkt fakta finns även en del forskningsresultat medtagna, som belyser de olika aspekterna på hållning av hundar.
  • Tapanainen, Timo (Helsingin yliopisto, 2007)
    Läpileikkaava näkökulma on tietokoneohjelman toteutukseen liittyvä vaatimus, jota ei voida toteuttaa käytetyllä ohjelmointikielellä omaan ohjelmayksikköön, vaan sen toteutus hajaantuu useisiin ohjelmayksiköihin. Aspektiohjelmointi on uusi ohjelmointiparadigma, jolla läpileikkaava näkökulma voidaan toteuttaa omaan ohjelmayksikköön, aspektiin. Aspekti kapseloi näkökulman toteutuksen neuvon ja liitoskohtamäärityksen avulla. Neuvo sisältää näkökulman toteuttavan ohjelmakoodin ja liitoskohtamääritys valitsee ne ohjelman liitoskohdat, joihin ohjelmakoodi liitetään. Nykyisillä aspektikielillä voidaan valita liitoskohtia pääasiassa niiden syntaktisten ominaisuuksien, kuten nimen ja sijainnin, perusteella. Syntaksiin sidoksissa olevat liitoskohtamääritykset ovat hauraita, sillä ohjelmaan tehdyt muutokset voivat rikkoa syntaksista riippuvia liitoskohtamäärityksiä, vaikka itse liitoskohtamäärityksiin ei tehtäisi muutoksia. Tätä ongelmaa kutsutaan hauraan liitoskohtamäärityksen ongelmaksi. Ongelma on merkittävä, koska hauraat liitoskohtamääritykset vaikeuttavat ohjelman kehitettävyyttä ja ylläpidettävyyttä. Tässä tutkielmassa perehdytään hauraan liitoskohtamäärityksen ongelmaan ja siihen esitettyihin ratkaisuihin. Tutkielmassa näytetään, että ongelmaan ei ole tällä hetkellä kunnollista ratkaisua.
  • Luoto, Sanna (Helsingfors universitet, 2011)
    The literature review dealt with celiac-toxic Triticeae prolamins and their enzymatic degradation. Also the immunochemical methods for prolamin analysis were introduced. The gluten-derived immunogenic peptides are proline-rich and thereby remarkably resistant to proteolytic degradation. Most of the triggering prolamins can, however, be degraded by combining endogenous cereal enzyme activity with acidic incubation. Despite of this residual prolamins still exist and their concentration exceeds the threshold considered to be safe for gluten intolerants. The objective of the experimental work was to further hydrolyse the residual prolamins present in malt autolysates of wheat, barley and rye, with a food grade proline endopeptidase from Aspergillus niger (AN-PEP). Size-exclusion chromatography (SEC), free amino nitrogen (FAN) and SDS-PAGE analysis determined the extent of protein hydrolysis. Actual prolamin degradation was observed with immunological methods. Hydrolysis of residual prolamins was extensive in all malt systems – more than 96% of the prolamins were hydrolysed. The SEC and FAN data revealed that continuation of the hydrolysis overnight converted the polypeptides into smaller hydrolysis products. According to enzyme-linked immunosorbent assay analyses, 22 h incubation decreased the prolamin contents of wheat and rye malt hydrolysates below the level of 100 mg/kg. This level was achieved with AN-PEP concentration of 35 ?L/g in relation to freeze-dried autolysate. According to the Codex Alimentarius, food products containing gluten up to 100 mg/kg can be labelled 'very low gluten' and thus included in coeliac diet. AN-PEP treated rye malt ingredient could especially be a promising low-gluten ingredient to enhance the flavour of often poor-quality gluten-free bread. Before commercial applications can be devised the potential as a flavouring agent as well as the clinical safety of the product must be evaluated.
  • Alm, Henna (Helsingfors universitet, 2011)
    Tutkimukseni tarkoituksena oli tutkia aspiraatiobiopsianäytteen herkkyyttä kohdunrungonsyövän diagnostiikassa suomalaisessa potilasaineistossa. Tutkimusaineistoni koostui potilaista, joilla on todettu kohdunrungonsyöpä hysterektomiassa 5.4.2006- 16.12.2008 välisenä aikana ja otettu aspiraatiobiopsianäyte vuoden sisällä ennen kohdunpoistoa. Potilastiedot hain Patologian laitoksen Q-Pati tietokannasta. Biopsian diagnoosin perusteella jaoin potilasaineiston kolmeen ryhmään: karsinooma, kompleksi atyyppinen hyperplasia ja karsinooman suhteen negatiivinen vastaus. Näissä ryhmissä tarkastelin edelleen, oliko biopsianäyte johtanut leikkaushoitoon tai jatkotutkimuksiin. Tutkimukseni mukaan biopsianäytteiden vastauksena oli 61% tapauksista karsinooma. Suoraan hysterektomiaan biopsianäytteen perusteella johtaneita tapauksia oli 82%, eli tapaukset joiden PAD-vastauksena oli karsinooma sekä kompleksit atyyppiset hyperplasiatapaukset, joissa epäiltiin karsinoomaa. Lopullinen herkkyys oli kuitenkin 97% sillä perusteella, että näissä tapauksissa biopsian vastaus johti hysterektomiaan joko suoraan tai jatkotutkimusten jälkeen kohtuullisen ajan (2kk) sisällä. Tutkimukseni mukaan aspiraatiobiopsia on luotettava testi epäiltäessä kohdunrungonsyöpää. Tulosten perusteella jatkotutkimukset ovat tarpeen, mikäli biopsian vastauksena on niukka näyte tai pyometra.
  • Jokinen, Nora (2013)
    Estimated 180 million people worldwide are infected by hepatitis C virus. It causes liver diseases which are often asymptomatic. Chronic infections can lead to liver cirrhosis, transplantation and hepatocellular carcinoma. Drug development was slow until 1999 when the first cell culture model with autonomously replicating subgenomic HCV replicon was developed. It expresses the viral proteins that are necessary in HCV replication. The current interest in exploring new medicines is concentrated to the essential viral proteins, such as the NS3/4A protease, NS3 helicase, NS5A and NS5B RNA polymerase. HCV belongs to the Hepacivirus genus. Due to its high variability there are at least seven genotypes and several subtypes. Genotype 1 is the most common and the most difficult to treat. The current standard of care continues 24-48 weeks and consists mainly of pegylated interferon alpha and nucleoside analogue ribavirin, both non-specific HCV medicines with severe adverse effects. In 2011 two new direct-acting antivirals, protease inhibitors telaprevir and boceprevir, were approved for the treatment of HCV. A vaccine against HCV has not yet been developed. The aim of this study was to optimize and validate a robust cell-based assay for screening of replication inhibitors against HCV. Genetically modified Huh-7 cells harbor a subgenomic HCV replicon expressing only the viral proteins needed in viral replication. In addition, the replicon encodes a firefly luciferase as a reporter gene. The amount of expressed luciferase is directly correlated with the amount of HCV replication making the replicon system suitable for HTS. The optimized and validated method was used for screening HCV replication inhibitors from a library containing 113 marine-derived substances. Marine environment has been in recent years a very interesting source for finding new drug candidates. This study was part of international MAREX project which aims to discover new active molecules from marine resources. A total of 37 samples (32.7%) exhibited antiviral activity over 50%. A cytotoxicity evaluation in ATP assay was performed with these samples. 10 samples (27.0%) exhibited cytotoxicity below 20%, of which six were synthetic samples and four were extracts. Compounds with high antiviral activity, low cytotoxicity and clear dose-response in further studies should be tested with a cell line expressing the full-length HCV genome. The structural proteins can exhibit some characteristics which inactivate the compound identified as active in the replicon system.