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  • a+b=b+a. 
    Reku, Juhani (2004)
  • Sunell, Matti (Helsingfors universitet, 2011)
    The study deals with the sound of pop music, as heard on a published recording. The sound of music is defined as such fundamental nature of musical materials which can be heard in a very short period of time, but which is also characteristic of music on a larger scale. Sound is investigated by analyzing features of music and sound which can be observed on a time scale of a few seconds. On the other hand, an attempt to describe a performer's characteristic sound is made through analysis of a larger sample of the repertoire. To describe the sound, traditional music analysis, commentary on instruments and recording techniques, analytical listening and spectrum analysis is used. The analytical listening methods applied here are Helmholtz's sound-colour classes and Lomax's cantometric scales which were originally used to classify singing styles. The history of spectrum (frequency content of sound) analysis as well as its application on music analysis is presented. The sonogram, which shows the distribution of acoustic energy at different frequencies and the change with respect to time, is introduced as an essential visualization tool. In the music analysis, three recordings of the group Abba are covered. Of them, 'Dancing Queen', which was recorded in 1975, gets the most thorough handling. The song is listened as a kind of longitudinal section, in separate frequency ranges, thereby revealing how each instrument or voice contributes to the overall sound. Based on listening and sonogram graphs, the song has been divided into 'sound situations' (or sonic situations). A sound situation is a period of music which is different from its surroundings in timbre, instrumentation or intensity (or their interaction). Each situation is presented in a combination of sonogram and score. A musical description of the sound situation is given, the singing is analyzed in cantometric terms and the timbre is described using Helmholtz's classes. Based on this analysis, the sound of Abba is characterized by strong treble content and brightness. The most important element of the sound is the singing of two female voices in combinations of unison and multiple layered harmonies. Spectrum analysis reveals that the music has especially much energy in the 4 5 kHz range. This is also the range in which human hearing is most sensitive. This emphasis, 'Abba-formant' , is most pronounced in choruses and brings a bright, penetrating tone to song.
  • Wissel, Gloria (Helsingin yliopisto, 2015)
    The main goal of this dissertation is to identify novel modulators acting on ATP Binding Cassette subfamily C member 2 (ABCC2) transporters and α2-adrenoceptors subtypes. With the purpose of identifying novel modulators and their mode of action, a combination of experimental and computational approaches have been used. The first protein presented in this dissertation is the ABCC2 transporter, also known as the multidrug resistance associated protein 2 (MRP2), an efflux transporter expressed in polarized cells where it effluxes a variety of both endogenous and exogenous molecules out of the cell. The most common way to study the interactions between small molecules and ABCC2 transporter is by a vesicle transport assay. Three assays are commercially available, which use different probes to define the ABCC2- transport. With the intent to define the different assays and identify the effect that small molecules have on the ABCC2-transport, a small set of eight compounds and, subsequently a larger library of compounds were tested with the different assays. Additionally, the aim was to identify and characterise novel ABCC2 inhibitors, 16 inhibitors have been identified from the larger library and classification models were built to identify important descriptors that were able to discriminate inhibitors from inactive molecules. Instant structure-activity relationships (SAR) of four scaffolds of ABCC2 modulators are also presented. In addition, some unpublished results are presented, the homology model of ABCC2 and further insights into the SAR of ABCC2 modulators. The other proteins included in this dissertation are the three subtypes of the α2-adrenoceptors, G-protein coupled receptors, involved in the signalling pathway of adrenaline and noradrenaline. A clear subtype characterization/profile of these proteins is not available. Selective molecules could be used in treatment of high blood pressure, in the alleviation of withdrawal symptoms, and as anaesthetic with fewer side effects than the current drugs. To define the affinity of a small set of antagonists and outline the involvement of the first transmembrane helix in ligand binding, a competition binding assay has been used with chimera receptors where the first transmembrane helix has been swapped between the three subtypes. Molecular modelling has been used to explain the different binding affinities to the chimera receptors. Additionally, the aim was to identify novel α2B-adrenoceptor selective compounds, thus a mid-sized library has been screened using a miniaturized binding assay. Hierarchical classification and chemoinformatics analysis has been used to visualize and analyse the screening results.
  • Väisänen, Enni (2010)
    Ligniini on maakasveille hyvin tärkeä makromolekyyli. Se on olennainen osa esimerkiksi vettä ja ravinteita kuljettavi-en puusolukon solujen soluseinää. Ligniini on myös osallisena kasvien puolustuksessa muita organismeja vastaan. Lisäksi se on tärkeä osa metsien ekologiassa ja ihmisen hyödykkeenä. Prosessia, jossa kasvisolun seinään muodostuu ligniiniä, sanotaan puutumiseksi, eli lignifikaatioksi. Tällöin lignifi-koituvan solun sisällä syntetoidut ligniinin monomeerit – monolignolit - kuljetetaan solukalvon yli soluseinään, jossa ne polymeroituvat ligniiniksi. Vähitellen kasvisolun soluseinän selluloosan, hemiselluloosien, pektiinien ja rakenne-proteiinien muodostama verkosto tukkiutuu ligniinistä. Lignifikoituessaan solu käy samalla läpi ohjelmoidun solukuo-leman. Monolignolien synteesistä tiedetään suhteellisen paljon, samoin kuin ligniinin polymerisaatiosta. Monolignolien kulje-tuksesta sen sijaan ei ole tietoa. Eri hypoteesien mukaan monolignolit voivat kulkeutua solukalvon yli joko diffuusion, golgin laitteen rakkuloiden tai kuljettajaproteiinien eli transportterien avulla. Teoria golgin laitteesta on osoitettu epä-todennäköiseksi ja diffusiostakaan ei ole todisteita aidoilla solu-kalvoilla. Siksi pro gradu – tutkielmani tarkoituksena onkin testata hypoteesia transportterivälitteisestä kuljetuksesta. Tutkittavina ovat kasveissa hyvin yleiset ABC-trans-portterit, joiden tiedetään kuljettavan sekundaarisen aineenvaihdunnan tuotteita. Tutkielmassani testasin ABC-transportterihypoteesia kuusen (Picea abies) ligniiniä tuottavilla A3/85-liuosviljelmäso-luilla sekä bioninformatiikan keinoin. A3/85-soluille syötettiin radioaktiivista fenyylialaniinia – monolignolisynteesin raaka-ainetta – yhdessä ABC-transportteri-inhibiittoreiden (Reversin 121 ja vana-daatti) kanssa. Inhibiittoreilla ei kui-tenkaan ollut vaikutusta solujen erittämien fenyylialaniinin fenolituotteiden tai näiden sokerijohdannaisten määrään. Bioinformatiikan keinoin taas yritettiin löytää kuusen (Picea spp.) ja männyn (Pinus spp.) EST-kirjastoista hyviä ABC-transportteriehdokkaita monolignolien kuljetukseen. Erityisesti lignifikoituvassa solukossa esiintyvää, ominai-suuksiltaan sopivaa ABC-transportteria ei kuitenkaan löyty-nyt. Tämän perusteella kuljetuksesta vastaa todennäköi-sesti jokin muu transportteri tai kuljetus ei tapah-du lainkaan transportterin välityksellä. Tutkielmassani oli testattavana myös usein esitetty ajatus monolignolien myrkyllisyydestä, josta ei kuitenkaan ole tehty asiaan kuuluvaa selvitystä. Monolignolien odotetulla myrkyllisyydellä saatetaan kasvitieteessä perustella eri-näisiä väittämiä, joten ajatuksen paikkansapitävyys on syytä varmistaa. Hypoteesia monolignolien myrkyllisyydestä testasin lisäämällä ligniiniä tuottamattomien tupakan (Nicotiana tabacum) liuosviljelmäsolujen (BY-2) kasvatusalustaan monolignoli koniferyylialkoholia. Koniferyylialkoholi aiheutti solujen lignifikaation sekä tappoi solut korkeissa pitoisuuksissa. Näiden kokeiden perusteella voidaan myrkyllisyys-hypoteesin sanoa olevan mahdollinen, joskin koniferyylialkoholin mahdollinen osallisuus lignifikoituvassa solussa tapahtuvaan ohjelmoituun solukuolemaan täytyy ottaa huomioon.
  • Hartama-Heinonen, Ritva (2008)
    This dissertation contributes to the fields of theoretical translation studies, semiotic translation theory, and the semiotics of translation. The aim of this work is to explore the alternative and potential which the semiotic approaches to translation entail from the viewpoint of contemporary translation studies. The overall objective is thus to show that a general semiotic translation theory, and in particular, a Peircean translation theory, are possible and indispensable. Furthermore, this study contributes to the semiotranslational approach and to its theory-building by developing the concept of abductive translation (studies). The specific theoretical frame of reference adopted in this study is provided by the semiotranslation introduced by Dinda L. Gorlée. This approach is primarily based on the semeiotic of Charles Sanders Peirce (1839 1914), and aims at a fusion of semiotics and translation studies. A more general framework is provided by the threefold background and material: the published and unpublished writings of Peirce, Peirce scholarship and Peircean-semiotic publications, as well as the translation-theoretical literature. Part One of this study concentrates on the justification, existence, and nature of the semiotic approaches to translation. This part provides a historical survey, a status report, and a discussion of this area of research, by employing the findings in a boundary-clearing that is multilayered both conceptually and terminologically. Part Two deals with Peircean semiotranslation. Here Gorlée s semiotranslational research is examined by focusing on the starting points, features, and development of semiotranslation. Attention is also paid to the state-of-the-art of semiotranslation theory and to the possibilities for future elaborations. Part Three focuses on the semiotranslational claim that translation is an abductive activity. The concept of abductive translation is based on abduction, one of Peirce s three modes of reasoning; at the same time Firstness, the category of abduction, becomes foregrounded. So abductive translation as a form of possibilistic translation receives here an extensive theoretical discussion by citing examples in which abduction manifests itself as (scientific) reasoning and as everyday contemplation. During this treatise, translation is first equated with sign action, then with interpretation and finally with reasoning. All these approaches appear to embody different facets of the same phenomenon Peirce s ubiquitous semiosis, and they all suggest that translation is inherently an intersemiotic activity in which a sign is inferred from another sign. Translation is therefore semiosis, semiosis is translation and interpretation, interpretation is reasoning, and so on ad infinitum all being manifestations of the art of marshalling signs. The three parts of this study are linked by the overall goal of abductive translation studies: investigation into abductive translation develops the theory of semiotranslation, and this enrichment of semiotranslation in turn constructs a semiotic paradigm within translation studies.
  • Paavola, Jere (Helsingin yliopisto, 2014)
    Heart disease is the biggest killer world-wide, causing a quarter of all deaths. During the past two decades, it has also risen above infectious diseases as the leading cause of years of life lost. Heart failure, characterized by weak pump function of the heart, and disturbances in heart rhythm (arrhythmias) are common and interrelated mechanisms underlying cardiac mortality. Intracellular calcium ions are crucial to contraction and relaxation of the heart muscle, as well as to control of its rhythm. How calcium is handled and regulated is thus essential to normal cardiac function, and disturbances in these processes can have catastrophic consequences. Understanding the mechanisms of these disturbances is important for improving disease prevention, diagnosis, and management. The studies in this thesis focus on two conditions where cardiac calcium handling is impaired. Studies I - III examine the mechanisms of a genetic arrhythmia disease named catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by stress-induced ventricular tachycardia in a structurally normal heart. Study IV investigates cardiac function in a model of another genetic disease, autosomal dominant polycystic kidney disease (ADPKD). This systemic disease mainly affects the kidneys, and the mechanisms of the concomitant decline in cardiac function have thus far remained underinvestigated. We evaluated clinical data on cardiac function of CPVT patients, including 24h electrocardiograms, intracardiac monophasic action potential recordings, and exercise stress tests. We used cell models to study the underlying disease mechanisms in detail. During conditions of stress, CPVT cells showed increased spontaneous and irregular release of calcium from within the intracellular stores through the cardiac ryanodine receptors. These receptors, which function as intracellular calcium release channels, harbor the disease-causing mutation. The spontaneous release of calcium led to changes in the membrane potential of the cells, manifested as afterdepolarizations during the resting phase of the cardiac cycle. These afterdepolarizations were reproduced in the clinical monophasic action potential recordings of CPVT patients, and were shown to trigger arrhythmias in these patients. Changes in intracellular calcium alter the membrane potential, and these changes are reflected on the electrocardiogram. Thus, irregularities that might correspond to those observed in the cell model were then investigated in 24h electrocardiograms of CPVT patients. Increased irregularity of cardiac repolarization was found in the CPVT patients. Such irregularity was greater in the electrocardiograms of CPVT patients with a history of more severe arrhythmic events. Additionally, we found slowed depolarization in response to stress in CPVT cells and patients, suggesting reduced conduction velocity might contribute to an arrhythmic substrate in these patients. Cardiac function in ADPKD caused by mutations in polycystin-2, another intracellular calcium channel, was investigated in a zebrafish model lacking expression of the polycystin-2 protein. The zebrafish lacking polycystin-2 showed signs of heart failure, including reduced cardiac output, edema, and arrhythmias. Hearts, which were then examined in more detail ex vivo, showed impaired cycling of intracellular calcium, which is likely to underlie the cardiac dysfunction observed in vivo. The association of ADPKD with idiopathic dilated cardiomyopathy (IDCM) was examined using the Mayo ADPKD Mutation Database, which contains data on genotyped ADPKD patients. Examination of the ADPKD Database showed IDCM to be very common among ADPKD patients. IDCM was most prevalent in patients with mutations in polycystin-2, suggesting impaired calcium cycling as a potential pathomechanism. Studies I-III shed new light on mechanisms of arrhythmias in CPVT and related conditions, opening the way for future studies on arrhythmia risk and therapeutic evaluation. Furthermore, the results encourage pursuing the novel stem cell models for studying pathomechanisms and therapeutics. Study IV showed an association between ADPKD and IDCM. The zebrafish model suggested impaired calcium cycling as an underlying mechanism, highlighting the usefulness of zebrafish as a model in cardiac research.
  • Hernesniemi, Sari (Helsingin yliopisto, 2012)
    Chronic myeloid leukemia (CML) is a hematologic malignancy that originates from pluripotent hematopoietic stem cells. The genetic abnormality underlying this disease, as well as a subtype of acute lymphoblastic leukemia (ALL), is a translocation between chromosomes 9 and 22, which leads to the formation of the Philadelphia (Ph) chromosome and the oncogenic BCR-ABL1 fusion protein. Targeted inhibition of the BCR-ABL1 protein with imatinib and other specific tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment and is currently regarded as the gold standard of targeted cancer therapy. In this doctoral thesis, different methodological approaches were used to characterize aberrant signaling activities in leukemic and normal cells with the ultimate aim of isolating novel prognostic markers for predicting TKI therapy outcome. First, the molecular mechanism of the disease was investigated in an ALL patient with a translocation between chromosomes 1 and 9. Cytogenetic characterization showed involvement of the ABL1 gene fused to an unknown gene. The RCSD1 gene was selected as a candidate and subsequent molecular dissection confirmed a RCSD1-ABL1 fusion. This novel fusion gene predicts sensitivity to TKI therapy in ALL patients. Second, several phosphoproteins related to immune cell function were analyzed both from the diagnostic phase CML patients and from patients under TKI therapy in order to reveal distinct signaling patterns. A single cell phosphoprotein method based on multiparameter flow cytometry was used to analyze phosphoprotein levels in different cell populations. The responsiveness of myeloid cells to ex vivo cytokine stimulation in diagnostic-phase patients was low, but was normalized in TKI-treated patients. In general, the blood leukocyte subsets responded normally to various cytokine stimulations, which indicated a non-immunosuppressive role for TKIs. This project also led to the development of a software assisted analysis program, which can conduct the whole range of flow cytometry data analysis, thereby diminishing the effort needed for manual cell population gating and interpretation. Lastly, biomarkers for therapy response were identified by analyzing aberrant signaling activities in leukemic cells collected at the time of diagnosis. The analysis was based on a phosphoproteomic array measuring phosphorylation of 46 different kinase targets. Several proteins had aberrant phosphorylation levels in patients with a poor therapy outcome − pSTAT5b being the most prominent. These biomarkers could be useful in guiding therapy selection at the time of diagnosis. In conclusion, the findings imply that TKI therapy responses can be linked to certain biological markers, which can possibly be utilized in clinical applications in the future.
  • Aarnio, Marja-Liisa (1968)
  • Freihoff, Roland (1963)
  • Kalinowski, Jaroslaw (2015)
    One of the goals of modern quantum chemistry is to simulate actual chemical experiments. In order to study species closer to real life systems and bulk environments there is a need for methodological developments. There are two ways to approach large systems with a given level of accuracy: conceptual changes to quantum chemistry methods or algorithmic developments for current methods. Many scientists believe that the conceptual changes truly increase the size of the systems one can study. With more or less advanced approximations to the method it is possible to increase the efficiency of calculations orders of magnitude. The implementation and algorithms fall down in the priority list, as advanced algorithmic developments are time consuming and usually lead to lower efficiency increases than conceptual changes. In this work it is shown that algorithmic developments cannot be neglected, and that even simple changes help in utilizing the power of modern computers and can also increase the efficiency by orders of magnitude. In this work new algorithmic developments are presented and used for solving various timely chemical problems.
  • Kemppainen, Lasse (1997)
  • Cleve, Beatrice (1993)
    Dessa fördjupade studier ingick som ett delprojekt i Veterinärmedicinska högskolans studentkårs biståndsprojekt i Etiopien sommaren 1990. Spontana aborter är ett ständigt problem bland kobesättningarna i Etiopien. I detta projekt undersöktes korpå en statlig gard, Stella farm, utanför Etiopiens huvudstad Addis Abeba. Efter uppsamling av data koncentrerades undersökningen tillanalys av fodret i avseende och vitaminer och spårämnen samtsvampgifter. Infektionssjukdomar som beaktades var brucellos,leptospiros och IBR ( Infectious Bovine Rhinotracheitis ).Samtliga laboratorieundersökningar gjordes vid SVA av författaren, förutom foderanalysen som gjordes vid Statensjordbrukskemiska anstalt. Korna var till 86,4 % positiva för IBR, fodret innehöllmykotoxiner och brist på jod och A-vitamin.Undersökningsresultaten har meddelats Etiopiensjordbruksministerium.
  • Väisänen, Heini Elena (Helsingfors universitet, 2010)
    Suomessa tehdään vuosittain noin 10 000 aborttia. Abortinjälkeistä hedelmällisyyttä on suomalaisessa tutkimuksessa tarkasteltu melko vähän etenkin yhteiskuntatieteellisesti, vaikka abortti koskettaa tuhansia naisia vuosittain. Tutkielmani tavoitteena on selvittää, millaista on abortinjälkeinen hedelmällisyyskäyttäytyminen, eli ketkä päätyvät uuteen aborttiin, ketkä synnytykseen ja ketkä eivät tule uudelleen raskaaksi. Tulosten perusteella päätellään, onko abortoivien joukossa erotettavissa ryhmiä, joille abortti voi muodostua yhdeksi ehkäisyn muodoksi ja keille se on kertaluontoinen tapahtuma. Tulokset sidotaan aiempaan teoreettiseen ja empiiriseen hedelmällisyystutkimukseen. Aineisto koostuu raskaudenkeskeytysrekisterin tiedoista vuosilta 2000–2008 ja siihen yhdistetyistä abortoineiden naisten syntymärekisteritiedoista samoilta vuosilta. Tutkielmassa tarkasteltiin niitä 63 763 naista, jotka tekivät seuranta-aikana ensimmäisen aborttinsa. Uuteen aborttiin heistä päätyi 7 743 ja synnytykseen 11 497 abortinjälkeisessä raskaudessaan. Ensimmäisen abortin (eli indeksiabortin) aikaisten taustamuuttujien vaikutusta seuraavan raskauden lopputulokseen analysoitiin elinaikamallinnuksen menetelmin (pääosin Coxin regressio). Lisäksi tarkasteltiin indeksiabortin ja uuden raskauden välillä mahdollisesti muuttuneen parisuhdestatuksen sekä sosioekonomisen aseman vaikutusta hedelmällisyyskäyttäytymiseen logistisen regressioanalyysin avulla. Tulosten avulla oli mahdollista erottaa toisistaan eritavoin abortin jälkeen käyttäytyviä ryhmiä. Uudelleen abortoivat erityisesti nuoret, lapsia jo saaneet, alemmassa sosioekonomisessa asemassa olevat ja sellaiset, joilla ei ollut parisuhdetta. Synnyttämään päätyivät 20–34-vuotiaat, opiskelunsa päättäneet, korkeassa sosioekonomisessa asemassa olevat, lapsettomat ja parisuhteessa olevat. Lisäksi maaseudulla asuminen lisäsi hieman synnytyksen todennäköisyyttä ja mikäli indeksiabortti oli tehty sikiön sairauden perusteella, todennäköisyys synnyttää kasvoi selkeästi. Raskaaksi tulivat harvemmin uudelleen yli 30-vuotiaat, lapsia saaneet ja korkeassa sosioekonomisessa asemassa olevat. Monet heistä olivat lisäksi leskiä tai eronneita. Mikäli indeksiabortin jälkeen opiskelija meni töihin, hänen synnytystodennäköisyytensä kasvoi selkeästi. Samoin kävi, jos indeksiabortin aikaan yksin elänyt muodosti uuden parisuhteen ennen toista raskauttaan. Saatujen tulosten perusteella on erotettavissa ryhmiä, joihin tulisi erityisesti kiinnittää huomiota jo ensimmäisen abortin aikaan, sillä heidän riskinsä abortoida uudelleen on muita korkeampi. Suurin vaikutus oli lapsimäärällä ja parisuhdestatuksella. Sosioekonomisen aseman sekä asuinalueen vaikutus jäi odotettua pienemmäksi, mutta ei kuitenkaan olemattomaksi.
  • Sairanen, Samuli (2013)
    The term "botnet" has surfaced in the media in recent years, showing the complications of manipulation of massive amounts of computers. These zombie computers provide platform for many illegal or otherwise shady actions, like spam mailing and denial of service-attacks. The power of such networks is noticeable on global scale, but what is really known about these networks? Why do they exist in the first place? How are botnets being created today and how they work on a technical level? How is the emergence of mobile internet computing affecting botnet creation and what kind of possibilities does it offer? Goal of this work is to illustrate the history of botnets, understand the structure of botnets, how they are built, and how they affect the whole internet culture. Also the methods for fighting against the threat of botnets are speculated.
  • Korpinen, Tuulikki (1938)
  • Elo, Johanna (Helsingin yliopisto, 2003)