Only Connect?: Aspects of Intertextuality in Zadie Smith's On Beauty

Tutkielma käsittelee intertekstuaalisuuden eri muotoja Zadie Smithin romaanissa On Beauty (suom. Kauneudesta). Tutkimuksen tarkoitus on osoittaa kuinka oleellisesti intertekstuaalisuuden teoria on vaikuttanut kirjallisuustieteen metodeihin ja postmoderniin kirjallisuuskäsitykseen, sekä käsitellä sen soveltuvuutta nykykirjallisuuden tutkimiseen analysoimalla teorian sisäistä monimuotoisuutta ja ristiriitoja. Tutkimusmateriaalina käytetään Smithin romaanin lisäksi E. M. Forsterin romaania Howards End (suom. Talo jalavan varjossa), johon On Beauty tietoisesti viittaa. Teoreettisena viitekehyksenä tutkielmassa toimii Gérard Genetten teoksessa Palimpsests sekä Roland Barthesin esseessä Tekijän kuolema esille tuodut kirjallisuusteoreettiset käsitykset. Valittu metodologia antaa mahdollisuuden hahmottaa intertekstuaalisuus kahdella eri tavalla: Genetten strukturalistinen lähestymistapa soveltuu teosten välisten viittaussuhteiden tutkimiseen, kun taas Barthesin jälkistrukturalistinen diskurssi auttaa ymmärtämään tekstienvälisyyden osana merkityksen jatkuvaa epävakautta. Tutkielman ensimmäinen osio keskittyy analysoimaan lähiluvun keinoin romaanien On Beauty ja Howards End välistä strukturalistista suhdetta vertailemalla teosten eroja ja yhtäläisyyksiä Genetten intertekstuaalisuusteorian valossa. Vertailussa kiinnetetään erityisesti huomiota teosten juoneen, rakenteeseen, aikaan ja paikkaan, sekä uudelleenkirjoitusten yleiseen tendenssiin päivittää alkuperäistä tarinaa kohdeyleisölle paremmin sopivaksi. Toisessa osiossa tutkimusta esille nousee jälkistrukturalistinen näkemys intertekstuaalisuudesta osana lukijan tuottaman merkityksen tulkinnanvaraisuutta. Osiossa käsitellään Rembrandtin taideteosten roolia Smithin romaanissa ja analysoidaan hahmojen tulkintoja sekä suhtautumista Rembrandtin tuotantoon Barthesin teoreettisten käsitteiden kautta. Keskeiseksi analyysin kohteeksi nousee lukija sekä lukijan tuottamat tulkinnat ja niiden merkitys Smithin romaanin tematiikassa. Tutkielmassa osoitetaan kuinka intertekstuaalisuus ei ole niin yksinkertainen termi kuin sen laaja käyttö niin kirjallisuustieteessä kuin mediassakin antaa ymmärtää, sekä selvitetään intertekstuaalisuuden teorian kehitystä 60-luvulta nykypäivään. Vaikka strukturalistisessa muodossa käsite soveltuu etenkin kahden toisiinsa kytkeytyneen teoksen tutkimiseen, vertaileva analyysi kuitenkin osoittaa, että On Beauty ei ole pelkkä uudelleenkirjoitus, vaan romaanin tulkintaan tarvitaan myös jälkistrukturalistisen dekonstruktion käsitteitä, jotta laajemmat tekstuaalisuuden verkostot aukeavat lukijalle. Romaanissa esiintyvä taitelijakuva myös osoittaa, että Smith itse on hyvin tietoinen kirjallisuusteoreettisesta keskustelusta.

Cyclin dependent protein kinases as drug targets – potential in cardiovascular diseases

Complications of atherosclerosis such as myocardial infarction and stroke are the primary cause of death in Western societies. The development of atherosclerotic lesions is a complex process, including endothelial cell dysfunction, inflammation, extracellular matrix alteration and vascular smooth muscle cell (VSMC) proliferation and migration. Various cell cycle regulatory proteins control VSMC proliferation. Protein kinases called cyclin dependent kinases (CDKs) play a major role in regulation of cell cycle progression. At specific phases of the cell cycle, CDKs pair with cyclins to become catalytically active and phosphorylate numerous substrates contributing to cell cycle progression. CDKs are also regulated by cyclin dependent kinase inhibitors, activating and inhibitory phosphorylation, proteolysis and transcription factors. This tight regulation of cell cycle is essential; thus its deregulation is connected to the development of cancer and other proliferative disorders such as atherosclerosis and restenosis as well as neurodegenerative diseases. Proteins of the cell cycle provide potential and attractive targets for drug development. Consequently, various low molecular weight CDK inhibitors have been identified and are in clinical development. Tylophorine is a phenanthroindolizidine alkaloid, which has been shown to inhibit the growth of several human cancer cell lines. It was used in Ayurvedic medicine to treat inflammatory disorders. The aim of this study was to investigate the effect of tylophorine on human umbilical vein smooth muscle cell (HUVSMC) proliferation, cell cycle progression and the expression of various cell cycle regulatory proteins in order to confirm the findings made with tylophorine in rat cells. We used several methods to determine our hypothesis, including cell proliferation assay, western blot and flow cytometric cell cycle distribution analysis. We demonstrated by cell proliferation assay that tylophorine inhibits HUVSMC proliferation dose-dependently with an IC50 value of 164 nM ± 50. Western blot analysis was used to determine the effect of tylophorine on expression of cell cycle regulatory proteins. Tylophorine downregulates cyclin D1 and p21 expression levels. The results of tylophorine’s effect on phosphorylation sites of p53 were not consistent. More sensitive methods are required in order to completely determine this effect. We used flow cytometric cell cycle analysis to investigate whether tylophorine interferes with cell cycle progression and arrests cells in a specific cell cycle phase. Tylophorine was shown to induce the accumulation of asynchronized HUVSMCs in S phase. Tylophorine has a significant effect on cell cycle, but its role as cell cycle regulator in treatment of vascular proliferative diseases and cancer requires more experiments in vitro and in vivo.

Dental identification and aspects of medico-legal investigations of the Finnish victims of the Sumatra-Andaman earthquake on 26 December 2004

Tsunami waves of the Sumatra-Andaman earthquake on 26 December 2004 claimed approximately 230 000 lives and started the biggest identification operation in Interpol's history. The aim of this study was to resolve methods of the identification and results received. The viewpoint is mainly that of forensic odontology, but also includes other means of identification and results of the medico-legal examination performed in Finland. Of the 5395 victims in Thailand, approximately 2 400 were foreigners from 36 nations including 177 Finnish nationals. Additionally, a Finnish woman perished in Sri Lanka and a severely injured man after the evacuation in a hospital. The final numbers of missing persons and dead bodies registered in the Information Management Centre in Phuket,Thailand, were 3 574 ante-mortem (AM) and 3 681 post-mortem (PM) files. The number of identifications by December 2006 was 3 271 or 89% of the victims registered. Of Finnish victims, 172 have been identified in Thailand and 163 repatriated to Finland. One adult and four children are still missing. For AM data, a list of Finnish missing persons including 178 names was published on 30 December 2004. By February 2005 all useful dental AM data were available. Five persons on the list living in Finland lacked records. Based on the AM database, for the children under age 18 years (n=60) dental identification could be established for 12 (20%). The estimated number for adults (n=112) was 96 (86%). The final identification rate, based on PM examinations in Finland, was 14 (25%) for children (n= 56) and 98 (90%) for adults (n= 109). The number of Finnish victims identified by dental methods, 112 (68%), was high compared to all examined in Thailand (43%). DNA was applied for 26 Finnish children and for 6 adults, fingerprints for 24 and 7, respectively. In 12 cases two methods were applied. Every victim (n=165) underwent in Finland a medico-legal investigation including an autopsy with sampling specimens for DNA, the toxicological and histological investigation. Digital radiographs and computed tomography were taken of the whole body to verify autopsy findings and bring out changes caused by trauma, autolysis, and sampling for DNA in Thailand. Data for identification purposes were also noted. Submersion was the cause of death for 101 of 109 adults (92.7%), and trauma for 8 (7.3%). Injuries were 33 times contributing factors for submersion and 3 times for trauma-based death. Submersion was the cause of death for 51 (92.7%) children and trauma for 4 (7.3%). Injuries were in 3 cases contributing factors in submersion and once in trauma-based death. The success of the dental identification of Finnish victims is mainly based on careful registration of dental records, and on an education program from 1999 in forensic odontology.

Basic and translational studies on species B adenoviruses

Human adenoviruses (Ads) have been classified into six species (A to F) currently containing 55 serotypes. For almost 2 decades vectors derived from group C serotype Ad5 have been extensively used for gene transfer studies. These Ad5 based vectors are able to efficiently infect many mammalian cell types (including both mitotic and post-mitotic cells) through interaction with a primary attachment receptor, the coxsackie and adenovirus receptor (CAR). Despite the many advantages of Ad5 based vectors a number of limitations have affected their therapeutic application to many diseases. Although they can transduce many tissue types, Ad5 based vectors are unable to efficiently transduce several potential disease target cell types, including hematopoietic stem cells and malignant tumor cells. Therefore, newer vectors have been developed based on Ad serotypes other than Ad5. This thesis focuses on species B Ads. Species B Ads are comprised of three groups based on their receptor usage. Group 1 of species B Ads (Ad16, 21, 35, 50) nearly exclusively utilize CD46 as a receptor; Group 2 (Ad3, Ad7, 14) share a common, unidentified receptor/s, which is not CD46 and which was tentatively named receptor X; Group 3 (Ad11) preferentially interacts with CD46, but also utilizes receptor X if CD46 is blocked. Species B group Ads are important human pathogens. Species B group 2 serotypes are isolated from patients with respiratory tract infections, whereas the Group 1 viruses are described as causing kidney and urinary tract infections. B-group Ad infections often occur in immunocompromised patients, including AIDS patients, recipients of bone marrow transplants, or chemotherapy patients. Recent studies performed in U.S. military training facilities indicate an emergence of diverse species B serotypes at the majority of sites. This included the group 1 serotype 21 and the group 2 serotypes 3, 7, and 14. CD46-targeting vectors derived from Ad35 and Ad11 are important tools for in vitro gene transfer into human stem cells, including hematopoietic stem cells and induced pluripotent stem cells. Ad35 and Ad11 have been used as tools for cancer therapy, because CD46 appears to be uniformely overexpressed on many cancers. Furthermore, receptor X-targeting vectors, i.e vectors derived from Ad3 or vectors containing Ad3 fibers have shown superior in the transduction of tumor cells both in vitro and in vivo and are currently being used clinically in cancer patients. While extensive basic virology studies have been done on Ad5, the information of species B group 1 interaction with CD46 is limited. Furthermore, the receptor for a major subgroup of species B Ads (receptor X) is unknown. The goal of this thesis was it therefore to better understand virological and translational aspects of species B Ads. The specific findings described in this thesis include i) the identification of CD46 binding sites within the Ad35 fiber knob, ii) the study of the in vitro and in vivo properties of Ad vectors with increased affinity to CD46. iii) the study of the receptor usage of a newly emergent Ad14a, iv) the identification of desmoglein 2 as the receptor for Ad3, Ad7, Ad11, and Ad14, v) the delineation of structural details of Ad3 virus interaction with DSG2, and vi) the analysis of functional consequences of Ad3-DSG2 interaction. As a result of these basic virology studies two Ad-derived recombinant proteins have been generated that can be used to enhance cancer therapy by monoclonal antibodies.